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 conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Objective To explore the effect of remote ischemic preconditioning (RIPC) on preoperative heart rate variability in patients with heart valves. Methods Patients scheduled to undergo on-pump cardiac valve surgery in the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, between January and July 2022 were initially enrolled. Eligible patients were randomly assigned at a 1 : 1 ratio to either the RIPC group or the control group. Relevant indicators of heart rate variability [standard deviation of NN interval (SDNN), standard deviation of mean value of NN interval in every five minutes (SDANN), mean square root of difference between consecutive NN intervals (RMSSD), percentage of adjacent RR interval>50 ms (PNN50), low frequency (LF) component, high frequency (HF) component and LF/HF] at 8 hours in the morning on the surgical day between two groups were compared. Results A total of 118 patients were initially assessed. After screening, 58 patients were excluded, and 60 patients provided written informed consent and were enrolled in the trial, with 30 allocated to the RIPC group and 30 to the control group. Seven patients in the control group and 5 patients in the RIPC group were subsequently excluded due to missing heart rate variability data resulting from cancelled operations. Finally, 23 patients in the control group and 25 patients in the RIPC group were included in the analysis. There was no statistical difference in baseline characteristics between the two groups, and there was no significant difference in heart rate variability 24 hours before intervention (P>0.05). After the intervention measures were taken, the comparison of the results of heart rate variability at 8 hours on the day of operation showed that SDNN and SDANN of patients in the RIPC group were higher than those in the control group, with statistical differences (P<0.05). Conclusion RIPC can stabilize the preoperative heart rate variability of patients undergoing cardiac valve surgery.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective: To investigate the status of condom use and its influencing factors among men who have sex with men (MSM), so as to provide a basis for improving condom utilization rates and AIDS prevention and control in this population. Methods: From May to October 2024, a snowball sampling method was employed to recruit MSM in Songjiang District, Shanghai Municipality. Self-administered questionnaires were used to collect data on demographic characteristics, AIDS-related knowledge, sexual behaviors, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), and condom use in the past six months. Multivariable logistic regression model was used to analyze the influencing factors for consistent condom use. Results: A total of 921 MSM were surveyed, with a median age of 29.00 (interquartile range, 9.00) years. Among them, 697 (75.68%) were aware of AIDS-related knowledge, 826 (89.69%) expressed willingness to use PrEP, and 835 (90.66%) were willing to use PEP. Additionally, 787 (85.45%) MSM reported their age at first homosexual intercourse as ≥18 years, while 519 (56.35%) reported consistent condom use in the past six months. Multivariable logistic regression analysis revealed that MSM who were aware of AIDS-related knowledge (OR=0.582, 95% CI: 0.423-0.801), willing to use PrEP (OR =0.611, 95% CI: 0.385-0.969), and whose age at first homosexual intercourse was <18 years (OR=0.480, 95% CI: 0.330-0.700) were less likely to consistent use condoms. Conclusion The proportion of consistent condom use among the MSM remains relatively low, which is primarily associated with AIDS-related knowledge, willingness to use PrEP, and the age at first homosexual intercourse.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

ObjectiveTo study the correlations between traditional Chinese medicine （TCM） syndromes and lipid metabolism in children with Wilson disease （WD）. MethodsClinical data and lipid metabolism indicators ［total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， apolipoprotein A1 （ApoA1）， apolipoprotein B （ApoB）， and lipoprotein a （Lpa）］ were retrospectively collected from 341 children with WD. The clinical data were compared among WD children with different syndromes， and the correlations between TCM syndromes and lipid metabolism in children with WD were analyzed. Least absolute shrinkage and selection operator （LASSO） regression was used for variable screening， and unordered multinomial Logistic regression was employed to analyze the effects of lipid metabolism indicators on TCM syndromes. ResultsThe 341 children with WD included 121 （35.5%） children with the dampness-heat accumulation syndrome， 103 （30.2%） children with the liver-kidney Yin deficiency syndrome， 68 children with the combined phlegm and stasis syndrome， 29 children with the spleen-kidney Yang deficiency syndrome， and 20 children with the liver qi stagnation syndrome. The liver-kidney Yin deficiency syndrome， combined phlegm and stasis syndrome， and spleen-kidney Yang deficiency syndrome had correlations with the levels of lipid metabolism indicators （P<0.05）. Lipid metabolism abnormalities occurred in 232 （68.0%） children， including hypertriglyceridemia （108）， hypercholesterolemia （23）， mixed hyperlipidemia （67）， lipoprotein a-hyperlipoproteinemia （12）， and hypo-HDL-cholesterolemia （22）. The percentages of hypertriglyceridemia and hypo-HDL-cholesterolemia varied among children with different TCM syndromes （P<0.05）. Correlations existed for the liver-kidney Yin deficiency syndrome with TG， TC， and HDL-C， the combined phlegm and stasis syndrome with TG， the spleen-kidney Yang deficiency syndrome with TG， TC， and LDL-C， and the liver Qi stagnation syndrome with TC and LDL-C （P<0.05， P<0.01）. ConclusionThe TCM syndromes of children with WD are dominated by the dampness-heat accumulation syndrome and the liver-kidney Yin deficiency syndrome， and dyslipidemia in the children with WD is dominated by hypertriglyceridemia and mixed hyperlipidemia. There are different correlations between TCM syndromes and lipid metabolism indicators， among which TG， TC， LDL-C， and HDL-C could assist in identifying TCM syndromes in children with WD.

Objective To determine the expression of FOXM1 and PLK1 in colorectal cancer tissues and their relationship with clinicopathological characteristics and prognosis of patients. Methods Sixty patients who underwent surgical resection of colorectal cancer were retrospectively selected. Colorectal cancer tissues and adjacent tissues (>5 cm from the margins of colorectal cancer tissues) were collected. Immunohistochemistry, Western blot, and qRT-PCR analyses were used to detect the expression levels of FOXM1 and PLK1 in colorectal cancer tissues. Human colon cancer HCT-116 cells were treated with FOXM1 inhibitor FDI-6, and the effect of downregulating FOXM1 on PLK1 expression levels was investigated by Western blot and qRT-PCR. Results FOXM1 and PLK1 were highly expressed in the cytoplasm of colorectal cancer cells, and the positive expression rate was significantly higher than those in adjacent tissues (P<0.05). FOXM1 expression was closely related to the degree of differentiation, TNM stage, lymph node metastasis, and invasion depth (all P<0.05). PLK1 expression was closely related to TNM stage, lymph node metastasis, and invasion depth (all P<0.05). The expression levels of FOXM1 and PLK1 in colorectal cancer tissues were positively correlated (r_s=0.373, P=0.003). Western blot and qRT-PCR results showed that the expression level of PLK1 decreased significantly after inhibition of FOXM1 expression. Patients with either FOXM1 or PLK1 expression alone, or with neither expressed, had significantly longer survival time and more favorable prognosis than those with FOXM1 and PLK1 co-expression. Conclusion FOXM1 and PLK1 are highly expressed in colorectal cancer tissues. FOXM1 may promote colorectal cancer through PLK1, and its high expression suggests poor prognosis of patients and may be a potential target for colorectal cancer.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.