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.

In the context of globalization,zoonosis prevention and control requires an integrated approach across human,animal,and environmental systems,including interdisciplinary and cross sectional collaboration,which impose heightened requirements for the core competencies among relevant professionals.By a systematic analysis of literature and policy documents,this study explored progress in the application of the One Health concept to the global prevention and control of zoonoses,with a focus on dissecting practi-cal achievements and empirical insights regarding policies promoting the development of core competencies among professionals in this field.By summarizing the existing core competency frameworks and their construction methods,this article also disscussed the guiding roles of existing frameworks,such as the"competencies for one health field epidemiology framework"and the"Ecohealth and One Health network competency framework"on the cultivation of professional talent.This work aimed at providing theoretical support for establishing a One Health-oriented competency framework in China,promoting multidisciplinary collaboration,offering scientific foundations for policy-making and talent cultivation,and contributing to achieving the strategic objectives of"Healthy China 2030"and the Sustainable Development Goals.

In the context of globalization,zoonosis prevention and control requires an integrated approach across human,animal,and environmental systems,including interdisciplinary and cross sectional collaboration,which impose heightened requirements for the core competencies among relevant professionals.By a systematic analysis of literature and policy documents,this study explored progress in the application of the One Health concept to the global prevention and control of zoonoses,with a focus on dissecting practi-cal achievements and empirical insights regarding policies promoting the development of core competencies among professionals in this field.By summarizing the existing core competency frameworks and their construction methods,this article also disscussed the guiding roles of existing frameworks,such as the"competencies for one health field epidemiology framework"and the"Ecohealth and One Health network competency framework"on the cultivation of professional talent.This work aimed at providing theoretical support for establishing a One Health-oriented competency framework in China,promoting multidisciplinary collaboration,offering scientific foundations for policy-making and talent cultivation,and contributing to achieving the strategic objectives of"Healthy China 2030"and the Sustainable Development Goals.

AIM To investigate the purification process for esculin,fraxin,esculetin and fraxetin in Fraxini Cortex by macroporous resin.METHODS Static adsorption experiment was applied to screening resin model,single factor test was adopted in the optimization of purification process,UPLC-QTOF-MS/MS was used for identifying main components,after which heatmap was drawn.RESULTS The optimal resin model was ADS-5.The optimal purification process was determined to be 1.1 BV for loading amount,0.75 g/mL for loading concentration,2 BV pure water for washing impurity,and 4 BV 25%ethanol for eluting effective constituents,coumarins demonstrated the total transfer rate,purity and yield of 84.42%,53.28%and 4.79%,respectively.Total 37 constituents were identified,among which coumarins and phenylethanol glycosides were mainly concentrated in 25%ethanol eluent,organic acids,iridoids and flavonoids were mainly concentrated in 95%ethanol eluent.CONCLUSION This stable,feasible and accurate method can characterize the distribution patterns of coumarins in Fraxini Cortex in different eluents of macroporous resin,which provides guidance for further related pharmaceutical research.

The study investigated the effect of casticin on the proliferation of non-small cell lung cancer(NSCLC) H322 cells and explored its molecular mechanism. Firstly, the cell counting kit-8(CCK-8) assay, colony formation assay, and EdU assay were used to detect the effect of casticin on the proliferation capacity of H322 cells under different concentrations and treatment durations. Then, glucose uptake, lactate production, extracellular pH, and oxygen consumption of H322 cells were measured before and after casticin treatment to analyze its impact on glycolysis in NSCLC H322 cells. Finally, real-time fluorescence quantitative PCR(RT-qPCR) and Western blot assays were performed to explore glycolysis-related molecules affected by casticin. The experiments showed that casticin inhibited the proliferation of NSCLC H322 cells in a dose-and time-dependent manner, with half-maximal inhibitory concentrations(IC_(50)) of 28.64 and 19.41 μmol·L~(-1) after 48 and 72 hours of treatment, respectively. Casticin also inhibited glucose uptake and lactate production in H322 cells, while increasing extracellular pH and oxygen consumption. Further investigation revealed that casticin inhibited the expression of glycolysis-related molecules, including glucose transporter 1(GLUT1), hexokinase 2(HK2), aldolase A(ALDOA), pyruvate kinase M2(PKM2), and hypoxia-inducible factor-1α(HIF-1α). Overexpression of HIF-1α was found to reverse the inhibitory effects of casticin on H322 cell proliferation and glycolysis. These findings suggest that casticin may regulate cellular glycolysis by inhibiting the expression of HIF-1α, thereby inhibiting the proliferation of NSCLC H322 cells. This study identifies a potential drug for the treatment of NSCLC and provides a direction for further research.
Humans ; Cell Proliferation/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Lung Neoplasms/drug therapy* ; Glucose/metabolism* ; Cell Line, Tumor ; Glycolysis/drug effects*

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To discuss the effect of Hashimoto’s thyroiditis (HT) on papillary thyroid carcinoma (РТС) .Methods:The clinical features and pathological characteristics of 682 patients who underwent surgical treatment for the first time from Sep. 1st,2019 to May. 1st, 2021 in Department of Thyroid, Breast and Hernia Surgery, and confirmed by postoperative pathology as papillary thyroid carcinoma were retrospectively analyzed. There were 189 male patients, and 493 female patients, 529 patients < 55 years old and 153 patients ≥55 years old. 476 patients were classified as PTC group and 206 patients as PTC combined with HT group. Chi square test was used to compare the difference between two groups in gender, age, thyroglobulin antibody, thyroid stimulating hormone, thyroid peroxidase antibodies, thyroid peroxidase, number of lesions, metastasis lymph node in central region, thyroid stimulating hormone receptor antibody, carcinoembryonic antigen, whether microcarcinoma, vascular invasion, glandular outside violation, capsule and lateral transfer analysis, ultrasonic calcification, etc. At the same time, all patients were divided into the group without central lymph node metastasis (345 cases) and the group with central lymph node metastasis (337 cases) . The χ 2 test was used to compare the differences between the two groups in terms of sex, age, number of lesions, microcarcinoma, vascular invasion, extradular invasion, capsular invasion, lateral cervical lymph node metastasis, ultrasonic calcification and so on, so as to analyze the differences in clinical characteristics between the two groups. Results:There were 206 cases (30.21%) in PTC combined with HT group and 476 cases (69.79%) in PTC without HT group. There were significant differences in gender (12/194 vs 177/299) ( P=0.000) , age (175/31 vs 354/122) ( P=0.002) , TgAb (115/91 vs 455/21) ( P=0.000) ,TSH (13/175/18 vs 33/429/14) ( P=0.004) , TPOAb (90/116 vs 422/54) ( P=0.000) , number of lesions (114/92 vs 325/151) ( P=0.001) and lymph node metastasis in central area (87/119 vs 250/226) ( P=0.014) between the two groups ( P < 0.05) , but there were no significant differences in TRAb (196/10 vs 461/15) ( P=0.171) , CEA (205/1 vs 469/7) ( P=0.478) , microcarcinoma (136/70 vs 309/167) ( P=0.781) , vascular invasion (4/202 vs 16/460) ( P=0.446) , extraglandular invasion (52/154 vs 108/368) ( P=0.470) , capsule invasion (149/57 vs 358/118) ( P=0.429) , lateral neck lymph node metastasis (31/175 vs 72/404) ( P=0.979) or ultrasonic calcification (157/49 vs 392/84) ( P=0.063) . Compared with PTC group, PTC combined with HT group had the characteristics of more women, younger age, high TgAb, high TSH, high TPOAb, multiple lesions and high proportion of non central lymph node metastasis. There were 345 cases (50.59%) without central lymph node metastasis and 337 cases (49.41%) with central lymph node metastasis. Gender (71/274 vs 118/219) ( P=0.000) , age (246/99 vs 283/54) ( P=0.000) , exadular invasion (66/279 vs 94/243) ( P=0.007) , number of lesions (240/105 vs 199/138) ( P=0.004) , microcarcinoma (259/86 vs 186/151) ( P=0.000) , calcification on ultrasound (250/95 vs 299/38) ( P=0.000) , and HT (119/226 vs 87/250) ) ( P=0.014) had statistical significance ( P<0.05) but had no statistical significance in capsule invasion (250/95 vs 257/80) ( P=0.256) or vascular invasion (10/335 vs 10/327) ( P=0.958) . In addition, patients in the group with central lymph node metastasis were more male, younger, with multiple lesions, exadenocarcinoma, less microcarcinoma, and calcification on ultrasound without hashimoto. Univariate analysis showed that gender, age, number of lesions, extraglandular invasion, calcification, microcarcinoma and Hashimoto had significant effects on lymph node metastasis in the central region; Multivariate analysis showed that the presence of microcarcinoma, ultrasonic calcification, Hashimoto and the number of lesions were independent risk factors for central lymph node metastasis. Conclusion:HT may promote the occurrence of PTC, but at the same time inhibit its development, so that PC patients with HT have a better prognosis.

Multiple organs are physiologically and pathologically interconnected during aging, and the brain plays a central role in this process. There is a direct two-way communication between the brain and the gut called “brain-gut interaction”, which is of great significance for the study of aging, and the molecular mechanism remains to be further studied. The aim of this study is to explore the mechanism of aging in the context of brain-gut interaction. The results of general physical signs of mice showed that the amount of exercise decreased, body weight and food intake decreased significantly in aged mice (P < 0. 001, P<0. 05). The thymus index of aged mice was significantly lower than that of normal mice (P< 0. 05), and the thymic pathological results showed that the thymic cortex of aging mice was thinner, the boundary between medulla and cortex was blurred, and the cells were loosely arranged. Metabolomics analysis revealed 317 differential metabolites in feces and 100 differential metabolites in hippocampus. The results of microbiome showed that Bacteroidetes and Firmicutes were the dominant phyla of gut microbiota. Bacteroidetes showed an upward trend and Firmicutes showed a downward trend after aging. KEGG pathway results showed that 26 metabolic pathways were related to the study of aging, among which galactose metabolism, ABC transporter and purine metabolism were of great significance for the brain-gut interaction. The results of Spearman correlation analysis of the three groups showed that the types of metabolites involved were mainly lipids and lipid-like molecules and organic acids and derivatives, and the gut microbiota involved were mainly Bacteroidetes and Firmicutes. In conclusion, the present study demonstrated that the synergistic changes between brain and gut in aging mice were related to the mechanism of aging, which provided new insights into the mechanism of aging process.

OBJECTIVE: To investigate the inhibitory effect of RSL3 on the proliferation, invasion and migration of cisplatinresistant testicular cancer cells (I-10/DDP) and the effect of carbenoxolone on the activity of RSL3 against testicular cancer. METHODS: MTT assay was used to evaluate the survival rate of I-10/DDP cells following treatment with RSL3 (1, 2, 4, 8, 16 or 32 μmol/L) alone or in combination with carbenoxolone (100 μmol/L) or after treatment with Fer-1 (2 μmol/L), RSL3 (4 μmol/L), RSL3+Fer-1, RSL3+carbenoxolone (100 μmol/L), or RSL3+Fer-1+carbenoxolone. Colony formation assay was used to assess the proliferation ability of the treated cells; wounding-healing assay and Transwell assay were used to assess the invasion and migration ability of the cells. The expression of GPX4 was detected using Western blotting, the levels of lipid ROS were detected using C11 BODIPY 581/591 fluorescent probe, and the levels of Fe²⁺ were determined with FerroOrange fluorescent probe. RESULTS: RSL3 dose-dependently decreased the survival rate of I-10/DDP cells, and the combined treatment with 2, 4, or 8 μmol/L RSL3 with carbenoxolone, as compared with RSL3 treatment alone, resulted in significant reduction of the cell survival rate. The combination with carbenoxolone significantly enhanced the inhibitory effect of RSL3 on colony formation, wound healing rate (P=0.005), invasion and migration of the cells (P < 0.001). Fer-1 obviously attenuated the inhibitory effects of RSL3 alone and its combination with carbenoxolone on I-10/DDP cells (P < 0.01). RSL3 treatment significantly decreased GPX4 expression (P=0.001) and increased lipid ROS level (P=0.001) and Fe²⁺ level in the cells, and these effects were further enhanced by the combined treatment with carbenoxolone (P < 0.01). CONCLUSION Carbenoxolone enhances the inhibitory effect of RSL3 on the proliferation, invasion and migration of cisplatin-resistant testicular cancer cells by promoting RSL3-induced ferroptosis.
Carbenoxolone/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/pharmacology* ; Ferroptosis ; Fluorescent Dyes/pharmacology* ; Humans ; Lipids ; Male ; Neoplasms, Germ Cell and Embryonal ; Reactive Oxygen Species ; Testicular Neoplasms

PURPOSE: The most popular surgical approach to manage Lisfranc fracture-dislocations is the double-incision approach, which frequently causes a variety of complications, such as skin necrosis, rotational malreduction of the first tarsometatarsal joint (TMTJ) and lateral column dorsoplantar malreduction of the TMTJ. We introduce a three-incision approach to treat Lisfranc fracture-dislocations with only minor postoperative complications and good foot function. METHODS: We prospectively selected 30 previously healthy patients, ranging from 18 to 60 years of age, but only 23 patients completed the follow-up and thus were finally included, with an average age of 38.1 ± 12.9 years. All patients have sustained Lisfranc fracture-dislocations involving all three-column; 13.0% (3/23) were Myerson classification type A (medial), 47.8% (11/23) were type A (lateral), and 39.1% (9/23) were type C2. All patients were treated via a three-incision approach: a long incision made along the lateral border of the second ray was used as a working incision to visualize and reduce the first three TMTJs, as well as to apply internal fixation instrumentation; a 2 cm medial incision was made at the medial side of the first TMTJ as an inspecting incision, ensuring good reduction of the first TMTJ in medial and plantar view; another 1 cm inspecting incision was made at the dorsal side of the fourth/fifth TMTJ to prevent sagittal subluxation of the lateral column. Mean ± SD was used for quantitative data such as operation time, follow-up time and foot function scores. Postoperative complications were documented, and foot function was evaluated using the American orthopaedic foot & ankle society score, foot function index and Maryland foot score at follow-up. The foot function of the injured foot and contralateral foot of the same patient was at the end of follow-up, and independent sample t-test was used for statistical analysis. RESULTS: The median operation time was 117.9 ± 14.6 min (range 93 - 142 min). All complications occurred within three months after the operation, and included delayed wound healing (17.4%), superficial infection (8.7%), complex regional pain syndrome (4.3%) and neuroma (4.3%). There was no case of postoperative skin necrosis or malreduction. At the end of follow-up of 14.1 ± 1.2 months (range 12-16 months), the median American orthopaedic foot & ankle society score of the operated foot was 89.7 ± 5.7, the median foot function index was 21.7 ± 9.9, and the median Maryland foot score was 88.7 ± 4.8. There were no significant differences between the operated and contralateral sides, in terms of foot function, at the end of followup (p > 0.05). CONCLUSION The three-incision approach can provide adequate visualization of all TMTJs to ensure anatomical reduction and offer sufficient working space to apply internal fixation instrumentation, which is effective in treating three-column Lisfranc fracture-dislocations with minor soft tissue complications and satisfactory functional recovery.
Humans ; Adult ; Middle Aged ; Retrospective Studies ; Fracture Fixation, Internal ; Joint Dislocations/surgery* ; Fracture Dislocation ; Surgical Wound ; Postoperative Complications ; Necrosis ; Treatment Outcome