1.The Role and Regulatory Mechanisms of FOXO1 in Hepatic Lipid Deposition
Meng JIA ; Fang-Hui LI ; Shi-Zhan YAN ; Ai-Ju LI ; Yi-Le WANG ; Pin-Shi NI ; Jia-Han HE ; Yin-Lu LI
Progress in Biochemistry and Biophysics 2026;53(4):905-919
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.
2.A systematic review on the integrated application of evidence-based narrative education and undergraduate nursing teaching
Nannan BAI ; Meng LI ; Qian LIANG ; Chou YAO ; Yan WANG ; Ju HAN ; Chenyang HOU ; Nana XING
Chinese Medical Ethics 2026;39(2):229-237
ObjectiveTo systematically evaluate the application of narrative education in undergraduate nursing teaching, to understand the current application status of narrative education, and to provide a theoretical basis for the subsequent establishment of a sound narrative education system. MethodsA systematic search was conducted for studies published in Chinese and English databases on applying narrative education to undergraduate nursing teaching, with the search period ranging from database inception to February 23, 2025. Literature was screened, and relevant information was extracted. A rigorous quality evaluation was conducted on the included studies, and a descriptive analysis was performed on their content. ResultsA total of 20 papers were included, involving 3,180 research subjects, all of whom were undergraduate nursing students. The results of descriptive analysis showed that the teaching model of narrative education primarily encompassed reading narrative works, watching films and videos, performing narrative scenarios, and writing reflective journals. The course setting and content covered pre-teaching preparation and in-teaching implementation. The evaluation of teaching effectiveness included the evaluation of teachers’ teaching methods (student evaluation/self-evaluation) and the evaluation of students’ learning effectiveness (course grade evaluation/humanistic care scale/empathy scale assessment, and others). ConclusionNarrative education combines abstract concepts with concrete clinical situations, which not only enriches students’ learning experiences but also enhances their humanistic literacy. Meanwhile, it provides teachers with opportunities to develop their narrative teaching skills, which requires them to possess profound professional knowledge and employ narrative techniques to guide students in reflection and critical thinking, thereby improving teaching quality and learning outcomes. Future efforts should consistently deepen the connotation research of narrative education and build a systematic nursing education system.
3.Safety and efficacy analysis of TACE combined with donafenib and PD-1 inhibitors in the treatment of unresectable hepatocellular carcinoma
Daqian HAN ; Wenze XU ; Chao LIANG ; Hao LI ; Shuguang JU ; Manzhou WANG ; Jiacheng WANG ; Yang-yang NIU ; Xinwei HAN ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(7):503-509
Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.
4.Clinical study of TACE combined with apatinib for advanced hilar cholangiocarcinoma
Daqian HAN ; Hao LI ; Chao LIANG ; Manzhou WANG ; Yangyang NIU ; Shuguang JU ; Jiacheng WANG ; Jianzhuang REN ; Xinwei HAN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(4):262-267
Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.
5.Safety and efficacy analysis of TACE combined with donafenib and PD-1 inhibitors in the treatment of unresectable hepatocellular carcinoma
Daqian HAN ; Wenze XU ; Chao LIANG ; Hao LI ; Shuguang JU ; Manzhou WANG ; Jiacheng WANG ; Yang-yang NIU ; Xinwei HAN ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(7):503-509
Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.
6.Clinical study of TACE combined with apatinib for advanced hilar cholangiocarcinoma
Daqian HAN ; Hao LI ; Chao LIANG ; Manzhou WANG ; Yangyang NIU ; Shuguang JU ; Jiacheng WANG ; Jianzhuang REN ; Xinwei HAN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(4):262-267
Objective:To study the safety and feasibility of transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hilar cholangiocarcinoma.Methods:Clinical data of 41 patients with hilar cholangiocarcinoma admitted to the First Affiliated Hospital of Zhengzhou University from November 2019 to October 2020 were prospectively collected, including 21 males and 20 females, aged (65.1±12.5) years. The drugs used for TACE were albumin paclitaxel and gemcitabine, which were performed once every four to six weeks for no more than six times. Apatinib were adminstered two days after each TACE. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events. Patients were followed-up by outpatient, inpatient or telephone review. Survival analysis was performed using the Kaplan-Meier method.Results:Hilar cholangiocarcinoma were confirmed in all 41 patients by pathology. All patients were treated with TACE for at least twice. Twenty-three patients achieved complete remission, 14 stable disease, and four partial remission, with an ORR of 56.1% and a disease control rate of 90.2%. The follow-up duration was (13.3±5.4) months without lost to follow-up. The median PFS was 9.0 months, the median OS was 14.0 months, the 1-year cumulative recurrence-free survival rate was 31.7%, and the 1-year cumulative survival rate was 65.9%. Treatment-related adverse events in this study were predominantly Clavien-Dindo grade 1 or 2, without grade 4 to 5.Conclusion:TACE combined with apatinib treatment could be safe and feasible for advanced hilar cholangiocarcinoma.
7.Clinical study of treating atlanto-axial joint disorder with against-lateral correction Tuina
Yubin JU ; Feicui ZENG ; Hua XING ; Xiaojie SU ; Qian YE ; Yimou HAN ; Jiayun SHEN ; Jiongwei ZHU ; Jue HONG
Journal of Acupuncture and Tuina Science 2025;23(4):336-343
Objective:To observe the clinical efficacy of against-lateral correction Tuina(Chinese therapeutic massage)in treating atlanto-axial joint disorder(AAJD)and imaging changes.Methods:A total of 142 patients with AAJD were recruited.They were randomly allocated to a trial group and a control group using the random number table method,with 71 participants in each group.The trial group was treated with against-lateral correction Tuina 3 times weekly.The control group was offered conventional physical traction therapy once daily.The interventions lasted 2 weeks in both groups.The two groups of participants were observed before and after treatment for their changes in the global pain scale(GPS)score,visual analog scale(VAS)score for dizziness assessment,cervical range of motion(ROM)in rotation,and the extent of atlanto-dental displacement.Results:The GPS and VAS scores dropped after treatment in both groups(P<0.05)and were lower in the trial group than in the control group after treatment and at the follow-up(P<0.05).Participants in the trial group achieved a significant increase in the cervical ROM in rotation after treatment and at the follow-up compared to the pre-treatment value(P<0.05)and surpassed the control group(P<0.05);the control group only showed an increase in the left-side rotation(P<0.05).After the intervention,neither the intra-group nor the between-group comparison revealed significant differences in the extent of atlanto-dental displacement(P>0.05),though the trial group presented an improving tendency.Conclusion:Compared to physical traction,the against-lateral correction Tuina method works more significantly in improving pain,dizziness,and ROM in AAJD patients.
8.Research progress on tumors associated with Li-Fraumeni syndrome
Shiqi ZHENG ; Huiru HAN ; Lu JU ; Guotao REN ; Ruifen WANG ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):369-373,379
Li-Fraumeni syndrome(LFS)is a rare autosomal dominant genetic disorder.Patients with LFS tend to develop tumors at a young age and are at risk of multiple types of cancer.The core pathogenic mechanism of LFS is germline mutation of the TP53 gene,which leads to loss of function of the p53 protein and an increase in the risk of tumor development.There are many tumor types closely related to LFS,including soft tissue sarcoma,osteosarcoma,brain tumors,breast cancer,and adrenocortical carcinoma.Although some common mutation sites of the TP53 gene in LFS patients have been identified,there are still differences in mutation sites among different patients,and the type of TP53 gene mutation may affect the clinical manifestations and prognosis of patients.Therefore,genetic testing for LFS patients to determine the specific mutation form of TP53 is of great significance.This article reviews the clinical patho-logical characteristics,treatment methods,and prognosis of LFS-related tumor patients,aiming to provide useful refer-ences for clinical practice.
9.Research progress of atypical teratoid/rhabdoid tumor of the central nervous system
Huiru HAN ; Lu JU ; Shiqi ZHENG ; Guotao REN ; Lifeng WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(3):380-384
Atypical teratoid/rhabdoid tumor(AT/RT)is a rare,highly malignant central nervous system tumor with a poor prognosis and often occurs in children under 3 years of age.In this article,the clinicopathological features,molecular subtypes,pathogenesis,treatment,prognosis,relevant clinical trials,and existing problems of AT/RT will be reviewed to deepen the understanding of AT/RT.
10.Phlorizin improves cecal inflammation and intestinal barrier damage induced by Salmonella typhimurium in mice
Tong LI ; Lijuan KONG ; Yanli FENG ; Ji CHENG ; Tianyuan JU ; Jiawen HAN ; Shoupeng FU ; Juxiong LIU ; Guiqiu HU ; Haolong ZHANG
Chinese Journal of Veterinary Science 2025;45(3):587-593
Forty adult male C57BL/6 mice were randomly divided into four groups:the control group,Salmonella typhimurium(S.typhimurium)(ST)group,phlorizin(PHZ)+S.typhimuri-um(ST)group,and PHZ(80 mg/kg)group,with 10 mice in each group.Morphological observa-tion,HE staining,ELISA,immunofluorescence and Western blot were performed,the results showed that PHZ significantly increased the cecal index,decreased the spleen index of S.typhi-murium-induced mice(P<0.05),and reduce the pathological damage of cecum in mice.Mean-while,PHZ treatment also significantly reduced colonization of S.typhimurium in the cecum,spleen,mesenteric lymph nodes and liver(P<0.05).The results of ELISA showed that PHZ treatment also significantly inhibited the S.ty phimurium-induced increase in the expression of IL-1β,INF-γ,TNF-a and IL-6 in the cecum of mice(P<0.05).Immunofluorescence and Western blot results showed that PHZ significantly increased the protein expression levels of Occludin,Claudin-3,and ZO-1 in the cecal barrier of mice induced by S.typhimurium(P<0.05).These results con-firmed that phlorizin could improve cecal inflammation and intestinal barrier damage induced by S.typhimurium in mice.

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