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.

Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft tissue infection that rarely involves the periorbital region. We report an unusual case of periorbital NF caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a previously healthy 48-year-old woman, originating from a neglected, recurrent hordeolum—an otherwise benign eyelid condition. The infection resulted in an extensive fullthickness defect of the upper eyelid and adjacent temporal area, presenting major reconstructive challenges. Reconstruction was performed using a radial forearm free flap combined with a buccal mucosal graft to restore both anterior and posterior lamellae, achieving functional eyelid protection and improved visual acuity. This case highlights the potential for seemingly minor, recurrent eyelid infections to progress rapidly to devastating NF even in the absence of systemic symptoms or risk factors. Early recognition and multidisciplinary management were critical to preventing further morbidity. To our knowledge, MSSA has not previously been reported as a causative agent of periorbital NF, underscoring the need for clinical vigilance and timely intervention in common eyelid conditions to avoid catastrophic complications.

This study aimed to assess the utilization trends of pulmonary rehabilitation (PR) among lung cancer patients in Korea using the National Health Insurance Service (NHIS) database (2017 to 2021). PR was introduced and covered under the NHIS in 2016, primarily for chronic obstructive pulmonary disease, but recent evidence suggests its benefits for lung cancer patients. Data extraction was based on Korea Informative Classification of Diseases 8th revision codes C33 and C34, with PR prescriptions identified by codes MM440 and MM290.Descriptive statistical analysis was performed, and propensity score matching was used for comparison between PR and non-PR groups. Results showed a significant increase in PR utilization, with the number of patients receiving PR (MM440) rising from 1,002 in 2017 to 3,723 in 2021, indicating a 3.7-fold increase. However, the proportion of patients receiving PR remained low at 2.9% in 2021. Enhanced access to PR services and improved evaluation strategies are essential for optimizing patient outcomes.

Purpose: To investigate the genetic characteristics of patients with non-syndromic retinitis pigmentosa (RP) analyzed at a single institution. Methods: We conducted a retrospective analysis of 63 patients clinically diagnosed with non-syndromic RP who underwent genetic testing. The clinical features of patients exhibiting the most common mutations, EYS and USH2A, were further assessed through routine ophthalmic examinations. Results: Of the 63 patients, 22 (34.9%) exhibited significant mutations. Notably, EYS and USH2A mutations were each found in 5 patients (7.9%); RP1 mutations were found in 4 patients (6.3%). The average ages at diagnosis were 38.8 years for EYS mutations and 41.8 years for USH2A mutations. The average best-corrected visual acuities were logMAR 0.08 for EYS mutations and logMAR 0.51 for USH2A mutations. Both mutation types showed a decrease in the normal macular area in fundus photographs with increasing age. In USH2A mutations, optical coherence tomography revealed a more pronounced reduction in central macular thickness and central foveal ellipsoid length compared with EYS mutations. Visual field tests indicated a reduction within the central 10° in 40% of EYS mutations and 60% of USH2A mutations. Electroretinography showed non-detectable responses in 2 individuals with EYS mutations and 4 individuals with USH2A mutations (40% and 80%, respectively). Conclusions EYS and USH2A mutations represented 45% of the genetically identified cases; affected patients typically were diagnosed in their 40s. EYS mutations tended to preserve retinal function and central foveal structure better than USH2A mutations.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

CRM 197(cross-reacting material 197),a naturally occurring mutant of diphtheria toxin,is a safe and effective vaccine vector and extensively used on developing conjugate or combined vaccines.The mutant loses its enzymatic activity,but fully retains its receptor-binding ability and immunogenicity.In current work,the diphtheria toxin mutant CRM 197 and its fusion proteins with the receptor-binding do-main of botulinum neurotoxin serotype E(EHc)were developed using genetic engineering technology.These recombinant proteins were confirmed by Western blotting and SDS-PAGE.BALB/c mice were im-munized with the CRM197-EHc and EHc-CRM197 fusion proteins,and their immunogenicity was evalua-ted.These two fusion protein molecules,CRM197-EHc and EHc-CRM197,as subunit vaccines,elicited a robust humoral immune response targeting both CRM197 and EHc antigens in the immunized mice.Compared to the mixture of CRM197 and EHc,the mice vaccinated with the fusion proteins(CRM197-EHc and EHc-CRM197)induced higher levels of anti-CRM197 antibodies,and the mice vaccinated with EHc-CRM197 also generated strongest anti-EHc antibodies.Consequently,as a carrier molecule in the fusion protein vaccine,EHc enhances the immunogenicity of CRM197 molecules.Likewise,CRM197 boosts the immunogenicity of EHc in the EHc-CRM197 fusion protein.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 in-flammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the met-formin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson stai-ning was performed to observe the morphology and fi-brosis of myocardial tissue.TUNEL staining was per-formed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP and β-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleaved-caspase-1,GSDMD and GSDMD-NT in myocardial tis-sue.Results DJC could alleviate myocardial patho-logical damage,reduce collagen deposition and apopto-sis,reduce the levels of blood glucose,blood lipid,myo-cardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP and β-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,prob-ably by inhibiting the activation of NLRP3 inflamma-somes,attenuating cardiomyocyte pyroptosis,and amel-iorating the inflammatory state.

Aim To predict and verify the potential mechanism of the compatibility of"ginseng-astragalus-pueraria"in protecting islet morphology and improving insulin resistance by using network pharmacology.Methods The active ingredients and targets of the horn medicine were obtained from three platforms:TC-MSP,TCMIP,and BATMAN.The targets of type 2 dia-betes mellitus(T2DM)were obtained from three plat-forms:TTD,OMIM,and disgeNET.The PPI network was constructed by using the STRING database and Cy-toscape 3.9.1;GO and KEGG analysis were per-formed;POCASA 1.1 was used to predict protein binding sites,and AutoDock Vina1.1.2 was used for docking and experimental verification.Results"Gin-seng-astragalus-pueraria"screened out 2 021 targets,of which 152 were closely related to T2DM,and 10 key genes and the AGE-RAGE signaling pathway were i-dentified.Molecular docking showed that quercetin had good binding to RAGE,INS,and PI3K.Experi-ments showed that the horn drug increased insulin binding rate and secretion index and reduced serum in-sulin level and insulin resistance index.These data benefited from"ginseng-astragalus-pueraria"reducing the expression of AGE-RAGE,activating PI3K-Akt,in-hibiting NF-κB,and reducing the expression of IL-6,IL-1β and TNF-α.Conclusion The study suggests that"ginseng-astragalus-pueraria"regulates the AGE-RAGE/PI3K-Akt/NF-κB signaling pathway,repairs damaged islet morphology,and improves insulin resist-ance.

CRM 197(cross-reacting material 197),a naturally occurring mutant of diphtheria toxin,is a safe and effective vaccine vector and extensively used on developing conjugate or combined vaccines.The mutant loses its enzymatic activity,but fully retains its receptor-binding ability and immunogenicity.In current work,the diphtheria toxin mutant CRM 197 and its fusion proteins with the receptor-binding do-main of botulinum neurotoxin serotype E(EHc)were developed using genetic engineering technology.These recombinant proteins were confirmed by Western blotting and SDS-PAGE.BALB/c mice were im-munized with the CRM197-EHc and EHc-CRM197 fusion proteins,and their immunogenicity was evalua-ted.These two fusion protein molecules,CRM197-EHc and EHc-CRM197,as subunit vaccines,elicited a robust humoral immune response targeting both CRM197 and EHc antigens in the immunized mice.Compared to the mixture of CRM197 and EHc,the mice vaccinated with the fusion proteins(CRM197-EHc and EHc-CRM197)induced higher levels of anti-CRM197 antibodies,and the mice vaccinated with EHc-CRM197 also generated strongest anti-EHc antibodies.Consequently,as a carrier molecule in the fusion protein vaccine,EHc enhances the immunogenicity of CRM197 molecules.Likewise,CRM197 boosts the immunogenicity of EHc in the EHc-CRM197 fusion protein.