AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

OBJECTIVE To systematically analyze the population pharmacokinetics （PPK） studies of lacosamide and expound the influential factors of its pharmacokinetics in different populations. METHODS PPK studies of lacosamide were collected by searching the databases， such as Web of Science， PubMed， Embase， Metasearch， CNKI， Wanfang Data and VIP， both in Chinese and English. Relevant data were extracted， and the Prediction Model Risk of Bias Assessment Tool was used to evaluate the quality of the PPK models in the included studies. RESULTS Among 8 studies ultimately included， 6 were retrospective studies and 2 were prospective studies； 5 studies involved pediatric patients. Seven studies adopted a one-compartment model， while 1 study utilized a two-compartment model. Four studies had a model quality rating of grade A， two of grade B and two of grade C， respectively. Body weight， renal function， and hepatic enzyme inducers were significant covariates influencing PPK of lacosamide. CONCLUSIONS The existing PPK studies of lacosamide are predominantly conducted in pediatric populations. Pharmacokinetic variability is mainly influenced by body weight， renal function， and hepatic enzyme inducers. However， most PPK studies have not conducted external validation， and the generalizability of the models remains to be confirmed.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, is the fastest-growing cause of chronic liver disease worldwide, affecting approximately 30% of the global population.Imaging is vital for detecting, quantifying, and monitoring hepatic steatosis—the defining abnormality of MASLD—and subsequent fibrosis—the key determinant of liver-related outcomes. This review summarizes the principles, clinical usage, efficacy, and advancements in various imaging modalities for the noninvasive assessment of hepatic steatosis and fibrosis, with an emphasis on ultrasound, CT, and MRI. Additionally, this review explores the evolving landscape of MASLD diagnostic approaches, including machine-learning techniques, opportunistic screening, standardized imaging guidelines, and therapies, emphasizing the pivotal role that radiologists can play in shaping these developments.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

OBJECTIVE To explore the clinical effect and safety of nicorandil combined with different doses of tirofiban in the treatment of elderly patients with acute ST-segment elevation myocardial infarction （STEMI）. METHODS A total of 162 elderly patients with STEMI admitted to our hospital from June 1， 2022 to June 1， 2024 were retrospectively enrolled. All patients received percutaneous coronary intervention （PCI） and conventional treatment of STEMI， and used nicorandil （5 mg each time， tid） and tirofiban. According to the use of tirofiban， the patients were divided into conventional-dose group （n＝104） and half-dose group （n＝58）. Patients in the conventional-dose group received an intracoronary injection of 10 μg/kg tirofiban， followed by intravenous infusion of 0.1 μg/（kg·min） for 48 h； patients in the half-dose group received an intracoronary injection of 5 μg/kg tirofiban， followed by intravenous infusion of 0.05 μg/（kg·min） for 48 h. Related indexes of PCI （the proportion of patients with grade 3 of thrombolysis in myocardial infarction， no reflow in infarct related artery， percentage decrease in total ST-segment elevation ＞50% on electrocardiogram 2 hours after PCI）， cardiac function parameters before and after treatment （troponin I， N-terminal pro-brain natriuretic peptide contents and left ventricular ejection fraction）， bleeding events during treatment （gingival bleeding， epistaxis， mucosal bleeding， gastrointestinal bleeding） and other adverse events （all-cause death， non-fatal reinfarction， hypotension， ventricular fibrillation， acute heart failure） were compared between 2 groups. RESULTS There were no significant differences in related parameters of PCI， cardiac function parameters after treatment， the incidences of gingival bleeding， epistaxis and gastrointestinal bleeding， the total incidence of bleeding events， or the incidence of other adverse events during treatment between 2 groups （P＞0.05）， but the incidence of mucosal bleeding in the conventional-dose group was significantly higher than the half-dose group （P＜0.05）. CONCLUSIONS The clinical effect of nicorandil combined with half-dose tirofiban in the treatment of elderly patients with acute STEMI is comparable to that of nicorandil combined with conventional dose of tirofiban， but the mucosal bleeding risk of the former is lower than that of the latter. Therefore， patients at risk of mucosal bleeding are more suitable to use the previous regimen.

Objective: To understand the association between weight-adjusted-waist index (WWI) and cardiopulmonary endurance among middle school students, so as to provide references for the improvement of cardiopulmonary endurance levels in adolescents. Methods: From June 2015 to December 2018 by using the method of purposive sampling, height, weight, waist circumference, and 20 m shuttle-run tests were measured among 44 870 adolescents aged 13-18 from Northeast, North, East, South, Southwest and Northwest of China. The WWI of the adolescents and the maximum oxygen uptake (VO 2max ) were calculated indirectly. The t-test and one way analysis of variance were used for comparison, and the curve regression analysis method was adopted to analyze the relationship between WWI and VO 2max . Results: For Chinese middle school students aged 13-18, the WWI was (9.35±1.02), the number of 20 m shuttle-run was (38.89±18.14) times, and VO 2max was (39.96±5.88) mL/(kg ·min -1 ). The differences of VO 2max between WWI quartile arrays of boys aged 13-18 were statistically significant ( F=15.19, 9.00, 14.97, 20.48, 28.13, 10.13 , P <0.01), girls had the same trend ( F=23.36, 16.61, 33.45, 32.96, 18.23, 19.36, P <0.01). There was an inverted U shaped curve relationship between WWI and cardiopulmonary endurance. When WWI was 8.5, the VO 2max level reached the highest, which was 40.07 mL/(kg ·min -1 ). Compared with girls, WWI in boys had a more significant impact on cardiopulmonary endurance. Conclusion Maintaining optimal WWI levels may enhance adolescents cardiopulmonary endurance.

Imaging plays a critical role in the management of chronic liver disease (CLD) because it is a safe and painless method to assess liver health. The widely used imaging techniques include ultrasound, computed tomography and magnetic resonance imaging. These techniques allow the measurement of fat deposition, iron content, and fibrosis, replacing invasive liver biopsies in many cases. Early detection and treatment of fibrosis are crucial, as the disease can be reversed in its early stages. Imaging also aids in guiding treatment decisions and monitoring disease progression. In this review, we describe the most common imaging manifestations of liver disease and the current state-of-the-art imaging techniques for the evaluation of liver fat, iron, and fibrosis.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.