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.

This paper reviews the current application status of big language model in nursing, the needs for information technology development in critical care nursing, the current application status of and future development direction of big language model in critical care nursing, as well as the risks and challenges faced, with a view to providing a reference for promoting the application of big language model in critical care nursing.

Dry eye is a chronic ocular surface disease caused by multiple factors. It is caused by the instability of tear film and the imbalance of the microenvironment of ocular surface, and may be accompanied by ocular surface inflammation, damage, and abnormal nerve sensation. The instability of tear film is its core characteristic. Mucin is an important component of the tear film and plays a role in stabilizing the tear film. The reduction of its secretion and the change of its structure lead to the occurrence and development of dry eye. The intracellular Ca2+ signal is the key to controlling the secretion of water and enzymes by exocrine glands. A decrease in the Ca2+ signal can cause dry eye. Conjunctival goblet cells are the main cells that secrete mucin. By activating the intracellular PLC-IP3-Ca2+ pathway, RyRs pathway, cAMP signaling pathway, P2X receptor, BLT1 and ChemR23 receptors, cholinergic receptor, and ALX signaling pathway, the content of Ca2+ can be increased, and the replenishment of mucin granules can be accelerated, thereby relieving the symptoms of dry eye. The Ca2+ signaling pathway may be an important target for the treatment of dry eye. This article reviews the role of mucin in dry eye and the influence of the Ca2+ signal on the secretion of mucin by conjunctival goblet cells.

This paper reviews the current application status of big language model in nursing, the needs for information technology development in critical care nursing, the current application status of and future development direction of big language model in critical care nursing, as well as the risks and challenges faced, with a view to providing a reference for promoting the application of big language model in critical care nursing.

Objective:To survey the status quo of family doctor work mode in Shanghai Xuhui district.Methods:Semi-structured and structured in-depth interviews were conducted in Shanghai Xuhui district from April to June 2021, 11 directors, 12 deputy directors in charge and 30 family doctors from 12 community health service centers participated in the survey and completed two stages and four sessions of interviews on the development of the integrated and high-quality family doctor work mode and the ways to realize and the challenges to face. The records of interviews were transcribed, sorted and analyzed using the Colaizzi 7-step analysis method.Results:The survey showed that the family doctor contracting was carried out in a large team mode in the whole district, mainly for the elderly, and most of contracted residents were not included in health management and follow-up services. The team was composed of family doctors and assistants, and the routine outpatient service was the main work pattern, and the regular services also included the chronic disease follow-up and health check-up for elderly. On the issue of how to output high-quality integrated services, the majority of doctors (12/13) believed that the contracted individual should be taken as the unit of fine service, carrying out overall health assessment, optimizing medication plan, lifestyle guidance, one-stop service in hospital, etc.; only one doctor suggested that the family should be the management unit. For upgrading the working mode and service quality, insufficient time and energy were the main obstacle. Public health work occupied a lot of working time, but it seemed not be transformed into favorable resources and conveniences in health management and services. The professional assistants should carry out some responsibility to save family doctor′s time. The survey suggests that informatization, service space, and sufficient drug supply are the keys for ensuring high-quality and high-efficiency integrated services.Conclusion:The organizational structure of the family doctor team in Shanghai Xuhui district is relatively mature, but the integrated and high-quality service output has not yet reached. It is necessary to make regional overall planning and increase efforts to achieve the integration of medical treatment and prevention, so as to gain time for family doctors to carry out high-quality services. At the same time, it is also necessary to cultivate effective family doctor assistants, provide an information work platform that matches the work attributes and goals of family doctors, open up an integrated health management service space, and ensure the full range supply of drugs.

OBJECTIVE: On the basis of sodium hyaluronate eye drops, to observe the clinical efficacy of acupuncture on dry eye and explore the effect mechanism of ocular surface protection. METHODS: A total of 80 patients with dry eye were randomly divided into an observation group and a control group, 40 cases in each group. The control group was treated with routine cleaning of eyelid margin, hot compress of eyes with warm towel, and external application of sodium hyaluronate eye drops for 5 weeks. On the basis of the treatment as the control group, the observation group was treated with acupuncture at Jingming (BL 1), Cuanzhu (BL 2), Chengqi (ST 1), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6), etc., once a day, 6 times a week for 5 weeks (30 times totally). Before and after treatment, SchirmerⅠtest (SⅠT), breaking up time (BUT), corneal fluorescent (FL) score, ocular surface disease index (OSDI) score, and the contents of IL-6 and TNF-α in tears were evaluated and the therapeutic effect was compared between the two groups. RESULTS: Compared with before treatment, SⅠT and BUT after treatment in the observation group were prolonged (P<0.05), the scores of FL and OSDI and the contents of IL-6 and TNF-α in tears were decreased (P<0.05). After treatment, SⅠT and BUT in the observation group were longer than the control group (P<0.05), and the scores of FL and OSDI and the contents of IL-6 and TNF-α in tears in the observation group were lower than the control group (P<0.05). The total effective rate in the observation group was 87.5% (35/40), which was higher than 45.0% (18/40) in the control group (P<0.05). CONCLUSION On the basis of sodium hyaluronate eye drops, acupuncture could improve the clinical symptoms of dry eye, promote the secretion of tears, prolong the tear film breaking up time, and reduce corneal damage, and effect mechanism may be related to the reduction of inflammatory response.
Humans ; Hyaluronic Acid ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Dry Eye Syndromes/therapy* ; Ophthalmic Solutions

Objective:To investigate the fertility needs and outcome of pregnancy in patients with young breast cancer in China.Methods:A retrospective cross-sectional investigation was conducted on 374 young breast cancer women from Cancer Hospital, Chinese Academy of Medical Sciences. Young patients with breast cancer were defined as patients who got initial diagnosis of breast cancer at age no more than 40 years old. We conducted a questionnaire survey and collected clinical data from medical chart. Logistic regression model was used to analyze the possible factors influencing patients′ fertility intention.Results:308 young women with breast cancer completed questionnaires, and the response rate was 82.4%. 81 patients (26.3%) had fertility needs after diagnosis. Of them, 6 cases took active measures to preserve fertility. 72 patients (23.4%) received fertility counseling during treatment. 7 patients were successfully pregnant, including four cases who delivered normally. Multivariate logistic regression analysis showed that patients under 35 years old ( OR=4.81), bachelor degree or above ( OR=3.26), receiving breast-conserving surgery ( OR=2.15) and childless patients ( OR=3.03) were more likely to have fertility needs after diagnosis of breast cancer (all P<0.05). Conclusions:The fertility needs of young breast cancer women in China are gradually increasing. Healthcare providers associated with tumor patients should actively offer corresponding fertility consultation and individualized diagnosis and therapy plans for patients with fertility needs.

Objective:To investigate the fertility needs and outcome of pregnancy in patients with young breast cancer in China.Methods:A retrospective cross-sectional investigation was conducted on 374 young breast cancer women from Cancer Hospital, Chinese Academy of Medical Sciences. Young patients with breast cancer were defined as patients who got initial diagnosis of breast cancer at age no more than 40 years old. We conducted a questionnaire survey and collected clinical data from medical chart. Logistic regression model was used to analyze the possible factors influencing patients′ fertility intention.Results:308 young women with breast cancer completed questionnaires, and the response rate was 82.4%. 81 patients (26.3%) had fertility needs after diagnosis. Of them, 6 cases took active measures to preserve fertility. 72 patients (23.4%) received fertility counseling during treatment. 7 patients were successfully pregnant, including four cases who delivered normally. Multivariate logistic regression analysis showed that patients under 35 years old ( OR=4.81), bachelor degree or above ( OR=3.26), receiving breast-conserving surgery ( OR=2.15) and childless patients ( OR=3.03) were more likely to have fertility needs after diagnosis of breast cancer (all P<0.05). Conclusions:The fertility needs of young breast cancer women in China are gradually increasing. Healthcare providers associated with tumor patients should actively offer corresponding fertility consultation and individualized diagnosis and therapy plans for patients with fertility needs.

Background: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferatoractivated receptor γ (PPARγ) expression with GDM in overweight or obese women. Methods: One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting. Results: The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ± 7.87 ng/mL vs. 25.85 ± 7.29 ng/mL, G2 vs. N2: 17.06 ± 6.74 ng/mL vs. 21.62 ± 7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM+ overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05). Conclusions Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

Objective:To investigate the molecular mechanism of Buyang Huanwu Tang in improving cerebral vasospasm after subarachnoid hemorrhage. Method:Eighty male Sprague-Dawley rats were randomly divided into sham operation group, model group, Buyang Huanwu Tang low and high dose (13, 26 g·kg^-1·d^-1) group. According to 10 mL·kg^-1, the drug was administered twice a day for 7 days. The subarachnoid hemorrhage model was made by double occipital pool injection method. The neurological function scores of rats in each group were evaluated at 1, 3, 5 and 7 days. The diameter of basilar artery was measured by hematoxylin-eosin (HE)staining. The expressions of phosphp-phosphoinositide 3-kinases(p-PI3K), phosphp-protein kinase B(p-Akt),endothelial nitric oxide synthase(eNOS) and neuronal nitric oxide synthase(nNOS) protein in basilar artery brain tissue were detected by Western blot. The expression of nitric oxide(NO) and endothelin-1(ET-1) in rat cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA). Result:Compared with sham operation group, the neurological function scores of the model group were significantly decreased (P<0.05), the diameter of the basilar artery was significantly reduced (P<0.05), and The expression of p-PI3K, p-Akt, eNOS, nNOS proteins of the basilar artery brain tissue were significantly decreased (P<0.05). The level of NO in the cerebrospinal fluid was significantly decreased (P<0.05), and the ET-1 was significantly increased (P<0.05).Compared with model group, the different doses in Buyang Huanwu Tang group (26,13 g·kg^-1·d^-1) increased the neurological function scores 3 to 5 days after treatment, and the basilar artery diameter was significant increased (P<0.05).The expression of p-PI3K, p-Akt and eNOS protein was significantly increased (P<0.05).The level of NO was significantly increased (P<0.05), and ET-1 was significantly decreased (P<0.05). Compared with low-dose group, the neurological scores of high-dose group were significantly increased after 7 days of treatment with Buyang Huanwu Tang (P<0.05), and the diameter of the basilar artery was significantly increased (P<0.05), p-PI3K, The expression of p-Akt and eNOS protein was higher (P<0.05), the increase of NO was more obvious (P<0.05), the decrease of ET-1 was more significant (P<0.05). Conclusion:The protective effect of Buyang Huanwu Tang on cerebral vasospasm after subarachnoid hemorrhage may be related to up-regulation of p-PI3K, p-Akt and eNOS expression in PI3K/Akt/eNOS signaling pathway, thereby increasing NO production.