Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Objective: To explore the influencing factors of anxiety symptoms and to construct a predictive model based on machine learning algorithms, so as to provide support for the prevention and management of anxiety symptoms among junior high school students. Methods: From April to May 2023, a stratified random cluster sampling method was adopted to select 8 176 junior high school students from Zhengzhou and Shangqiu citys. All participants completed the Adolescent Self rating Life Events Checklist, the 10item Connor-Davidson Resilience Scale, the School Connectedness Scale, the Parent-Child Cohesion Questionnaire, and the 7 item Generalized Anxiety Disorder Scale. Logistic regression analysis identified the associated factors of anxiety symptoms among junior high school students. Predictive models were constructed using Logistic regression, Random Forest, and eXtreme Gradient Boosting (XGBoost) algorithms, with SHapley Additive exPlanations analysis explaining the optimal model. Results: The detection rate of anxiety symptoms among junior high school students was 16.3%. Logistic regression analysis showed that junior high school students who were female ( OR =1.22), in the ninth grade ( OR =1.27), living in urban areas ( OR =1.37), having a father with a college education or above ( OR =1.26), having a mother with a senior high school education ( OR =1.26), and experiencing higher levels of negative life events ( OR =1.05) reported a higher risk of anxiety symptoms(all P <0.05). In contrast, those with moderate family economic status ( OR =0.71), moderate academic burden ( OR =0.59), low academic burden ( OR =0.54), moderate sleep quality ( OR =0.46), good sleep quality ( OR =0.26), excellent sleep quality ( OR =0.15), higher levels of psychological resilience ( OR =0.96), higher levels of school connectedness ( OR =0.96), and higher levels of parent-child cohesion ( OR =0.98) reported a lower risk of anxiety symptoms (all P <0.05). Three machine learning models demonstrated good predictive performance for anxiety symptoms among junior high school students (all AUC>0.8), with the XGBoost model achieving the best predictive performance. SHAP analysis revealed that negative life events, sleep quality, school connectedness, psychological resilience and parent-child cohesion were the top five relevant factors for predicting anxiety symptoms. Conclusions The detection rate of anxiety symptoms among junior high school students is relatively high. The XGBoost model is the optimal predictive model for anxiety symptoms in the population. Negative life events, sleep quality, school connectedness, psychological resilience, and parent-child cohesion are significant correlates of anxiety symptoms among junior high school students.

ObjectiveTo observe the clinical efficacy and safety of Huatan Quyu formula in treating cerebral small vessel disease （CSVD） with phlegm and blood stasis blocking collateral pattern via randomized controlled trial， and explore its mechanism of improving CSVD by regulating glymphatic system （GS） circulation. MethodsSixty-eight CSVD patients with phlegm and blood stasis blocking collateral pattern in the Department of Encephalopathy， Affiliated Hospital of Shaanxi University of Chinese Medicine from April to December 2024 were selected and randomly divided into an experimental group （34 cases） and a control group， with 34 cases in each group. Both groups received basic Western medicine treatment， while the experimental group additionally received Huatan Quyu formula. After a course of 12 weeks， the following parameters were compared between the two groups before and after treatment. Clinical outcomes were assessed using the Tinetti performance-oriented mobility assessment （POMA）， Montreal Cognitive Assessment （MoCA）， Scales for Outcomes in Parkinson's Disease-Autonomic （SCOPA-AUT）， and traditional Chinese medicine （TCM） syndrome scores of phlegm and blood stasis blocking collateral pattern. Perivascular space （PVS） in the frontal lobe/basal ganglia and cerebrospinal fluid （CSF） flow parameters in the cerebral aqueduct were evaluated by 3.0T brain MRI， cerebrospinal fluid flow imaging， and phase-contrast magnetic resonance imaging （PC-MRI）. Then， safety indicators were monitored， and SPSS 25.0 was used for statistical analysis. ResultsSixty-four patients completed the study （32 in each group）. ①Baseline data： No statistically significant difference was found between the two group. ②Efficacy indicators： After treatment， the experimental group exhibited significantly improved total POMA， SCOPA-AUT， and TCM syndrome scores （P<0.01）， outperforming the control group （P<0.05）. No significant change was observed in MoCA scores between the two groups. ③Imaging indicators： The experimental group showed a reduced PVS area alongside significantly increased CSF flow parameters （including downward flow during the systolic period， and upward flow during the diastolic period） （P<0.01）， which were superior to the control group （P<0.01）. ④Safety： The laboratory indicators were normal in both groups， with no drug-related adverse reactions. ConclusionFor CSVD patients with phlegm and blood stasis blocking collateral pattern， Huatan Quyu formula can safely and effectively improve motor function， autonomic nerve function， and TCM syndromes， with potential mechanisms related to pulsatile CSF flow enhancement and GS circulation efficiency improvement.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Lung transplantation is a definitive treatment for end-stage lung disease and can significantly improve patient prognosis. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury and chronic lung allograft dysfunction intertwine to form a complex pathological network, posing persistent challenges to long-term patient survival. In 2025, research teams worldwide have made systematic progress in the field of basic lung transplantation research. By integrating cutting-edge technologies including single-cell multi-omics, spatial transcriptomics and novel animal models, significant breakthroughs have been achieved in the evolutionary dynamics of drug-resistant infections, molecular mechanisms of immune regulation, programmed cell death, optimization of donor lung protection strategies and early warning of chronic lung allograft dysfunction. This article systematically reviews the representative advances in basic lung transplantation research worldwide in 2025, and deeply analyzes the implications of mechanistic breakthroughs for optimizing diagnosis and treatment strategies, aiming to anchor the direction for innovative breakthroughs and clinical translation in basic lung transplantation research.

For HCQ retinopathy with CME, acupuncture combined with periocular injection can be used to improve the CME and protect the central vision. Subsequent research endeavors involving a more extensive cohort and extended observation periods are warranted to evaluate the effectiveness and safety profile of the intervention.
Humans ; Macular Edema/drug therapy* ; Acupuncture Therapy/methods* ; Hydroxychloroquine/therapeutic use* ; Female ; Retinal Diseases/chemically induced* ; Middle Aged ; Combined Modality Therapy ; Male

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.