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.Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma.
Dongyuan SU ; Biao HONG ; Shixue YANG ; Jixing ZHAO ; Xiaoteng CUI ; Qi ZHAN ; Kaikai YI ; Yanping HUANG ; Jiasheng JU ; Eryan YANG ; Qixue WANG ; Junhu ZHOU ; Yunfei WANG ; Xing LIU ; Chunsheng KANG
Acta Pharmaceutica Sinica B 2025;15(7):3632-3645
The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.
3.Efficacy of surgical resection and radiofrequency ablation in the treatment of difficult-to-reach hepatocellular carcinoma
Ju MA ; Yongnian REN ; Ying ZHU ; Yang XU ; Wensen WANG ; Xinyan ZHU ; Jinhui ZHAN ; Shipeng LI ; Dongxiao LI ; Liancai WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2025;31(6):433-437
Objective:To compare the efficacy of surgical resection and radiofrequency ablation (RFA) treatment for China liver cancer staging (CNLC) Ia hepatocellular carcinoma (HCC) at difficult-to-reach locations.Methods:A retrospective analysis was conducted on the clinical data of 114 patients with CNLC Ia HCC at Ⅶ、Ⅷ、Ⅳb or Ⅰ segments that were difficult-to-reach locations who were admitted to People's Hospital of Zhengzhou University from December 2018 to December 2023. Among the patients, 85 were males and 29 were females, aged (58.1±1.0) years. The patients were divided into two groups: a RFA group with 31 cases and a surgical resection group with 83 cases. Compare the levels of alanine transaminase (ALT) and aspartate transaminase (AST) before and after surgery, the surgical time, intraoperative blood loss, postoperative hospital stay, postoperative complications, recurrence free survival rate, and cumulative survival rate between the two groups.Results:The comparison of age, gender, ALT, and AST between the two groups showed no statistically significant differences (all P>0.05). The differences in ALT and AST levels before and after surgery in the RFA group were (134.8±38.7) U/L and (195.1±53.9) U/L, respectively, which were significantly lower than those in the surgical resection group [(226.8±17.9) U/L and (229.5±16.2) U/L] ( t=-2.45 and -1.12, P=0.016 and 0.041). The RFA group had shorter operation time [(69.2±11.7) min vs. (210.6±8.9) min], less intraoperative blood loss [(8.7±3.8) ml vs. (238.6±20.8) ml], and shorter postoperative hospital stays [(6.4±1.0) d vs. (13.1±0.4) d] compared to the surgical resection group, with all differences statistically significant (all P<0.05). The overall complication rates were 19.4% (6/31) in the RFA group and 22.9% (19/83) in the surgical resection group, showing no significant difference ( χ2=0.16, P=0.685). No statistically significant diffe-rence was found in recurrence-free survival rates between the two groups ( χ2=0.13, P=0.717). Similarly, there was no statistically significant difference in cumulative survival rates between the groups ( χ2<0.01, P=0.978). Conclusion:For HCC at CNLC Ⅰa in challenging locations, RFA demonstrated shorter operation time and postoperative hospital stay, less intraoperative bleeding, and superior liver function recovery compared with surgical resection, while no significant difference was observed in survival outcomes between the two treatment groups.
4.Efficacy of surgical resection and radiofrequency ablation in the treatment of difficult-to-reach hepatocellular carcinoma
Ju MA ; Yongnian REN ; Ying ZHU ; Yang XU ; Wensen WANG ; Xinyan ZHU ; Jinhui ZHAN ; Shipeng LI ; Dongxiao LI ; Liancai WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2025;31(6):433-437
Objective:To compare the efficacy of surgical resection and radiofrequency ablation (RFA) treatment for China liver cancer staging (CNLC) Ia hepatocellular carcinoma (HCC) at difficult-to-reach locations.Methods:A retrospective analysis was conducted on the clinical data of 114 patients with CNLC Ia HCC at Ⅶ、Ⅷ、Ⅳb or Ⅰ segments that were difficult-to-reach locations who were admitted to People's Hospital of Zhengzhou University from December 2018 to December 2023. Among the patients, 85 were males and 29 were females, aged (58.1±1.0) years. The patients were divided into two groups: a RFA group with 31 cases and a surgical resection group with 83 cases. Compare the levels of alanine transaminase (ALT) and aspartate transaminase (AST) before and after surgery, the surgical time, intraoperative blood loss, postoperative hospital stay, postoperative complications, recurrence free survival rate, and cumulative survival rate between the two groups.Results:The comparison of age, gender, ALT, and AST between the two groups showed no statistically significant differences (all P>0.05). The differences in ALT and AST levels before and after surgery in the RFA group were (134.8±38.7) U/L and (195.1±53.9) U/L, respectively, which were significantly lower than those in the surgical resection group [(226.8±17.9) U/L and (229.5±16.2) U/L] ( t=-2.45 and -1.12, P=0.016 and 0.041). The RFA group had shorter operation time [(69.2±11.7) min vs. (210.6±8.9) min], less intraoperative blood loss [(8.7±3.8) ml vs. (238.6±20.8) ml], and shorter postoperative hospital stays [(6.4±1.0) d vs. (13.1±0.4) d] compared to the surgical resection group, with all differences statistically significant (all P<0.05). The overall complication rates were 19.4% (6/31) in the RFA group and 22.9% (19/83) in the surgical resection group, showing no significant difference ( χ2=0.16, P=0.685). No statistically significant diffe-rence was found in recurrence-free survival rates between the two groups ( χ2=0.13, P=0.717). Similarly, there was no statistically significant difference in cumulative survival rates between the groups ( χ2<0.01, P=0.978). Conclusion:For HCC at CNLC Ⅰa in challenging locations, RFA demonstrated shorter operation time and postoperative hospital stay, less intraoperative bleeding, and superior liver function recovery compared with surgical resection, while no significant difference was observed in survival outcomes between the two treatment groups.
5.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
6.Construction and validation of a Nomogram model of intracranial infection after neurosurgery
Xiao-Ju MA ; Ying YU ; Yan LU ; Song-Qin LI ; Juan LIU ; Zheng WANG ; Feng ZANG ; Hui-Ping HUANG ; You-Peng CHEN ; Yong-Xiang ZHANG ; Wei-Hong ZHANG ; Zhan-Jie LI
Chinese Journal of Infection Control 2023;22(12):1483-1492
Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96%.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P>0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P<0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.
7.Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis.
Liang PAN ; Wen-Jie LU ; Zhan-Ying HAN ; San-Cong PAN ; Xi WANG ; Ying-Guang SHAN ; Meng PENG ; Xiao-Fei QIN ; Guo-Ju SUN ; Pei-Sheng ZHANG ; Jian-Zeng DONG ; Chun-Guang QIU
Journal of Geriatric Cardiology 2023;20(10):716-727
BACKGROUND:
Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy.
METHODS:
We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses.
RESULTS:
Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant.
CONCLUSIONS
The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.
8.Safety and efficacy of dual guiding catheter kissing technique in the treatment of stent partially dislodgement in coronary artery.
Zhan Ying HAN ; Ying Guang SHAN ; Wen Jie LU ; Xiao Fei QIN ; Guo Ju SUN ; Xi WANG ; Liang PAN ; Wen Cai ZHANG ; Chun Guang QIU
Chinese Journal of Cardiology 2022;50(9):895-899
Objective: To investigate the safety and efficacy of dual guiding catheter kissing technique (DCK) in the treatment of stent partly dislodgement in coronary artery. Methods: The study retrospectively involved 6 hospitalized patients with coronary artery stent partly dislodgement during PCI at The First Affiliated Hospital of Zhengzhou University from February 2016 to June 2019, DCK was used in these patients. We observe the success rate of stent retrieval, success rate of PCI, incidence of complications and major adverse cardiovascular events in 1 year follow up. Results: 6 patients were involved, of which 3 are male, ages range 49 to 68 years old, 4 patients are diagnosed with unstable angina, the other two are stable angina. All the partially disloged stents in the 6 patients were successfully removed from coronary artery. Except for 1 patient who refused coronary artery stenting again, the other 5 patients were successfully implanted coronary artery stenting. No serious complications occurred, no patients died and no major adverse cardiovascular events happened during 1 year follow up. Conclusions: DCK is safe and effective to remove partially dislodged stent in coronary artery.
Aged
;
Angina, Unstable
;
Angioplasty, Balloon, Coronary/methods*
;
Catheters
;
Coronary Vessels/surgery*
;
Female
;
Humans
;
Male
;
Middle Aged
;
Percutaneous Coronary Intervention
;
Retrospective Studies
;
Stents/adverse effects*
9.Research advances in chemical constituents and pharmacological activities of Dendrobium plants.
Ju-Run ZHAO ; Yi-Han WANG ; Yan JIN ; Chao JIANG ; Zhi-Lai ZHAN
China Journal of Chinese Materia Medica 2022;47(9):2358-2372
Dendrobii Caulis are commonly used tonic Chinese medicinal materials with a long history of application. As demonstrated by pharmacological results, the chemical constituents and the extracts of Dendrobii Caulis have anti-inflammatory, antibacte-rial, antioxidant, and anti-tumor effects, and can also regulate immunity, lower blood pressure, and regulate blood sugar. The active ingredients contained are widely concerned by scholars. This paper comprehensively summarized the chemical constituents and pharmacological activities of Dendrobium plants reported so far. The chemical constituents isolated from Dendrobium plants are mainly alkaloids, sesquiterpenoids, flavonoids, fluorenones, coumarins, bibenzyls, phenanthrenes, lignans, steroids, phenols, and polysaccharides. This paper is expected to provide a reference for further research, development, and utilization of Dendrobium plants.
Alkaloids
;
Antioxidants/pharmacology*
;
Dendrobium
;
Flavonoids
;
Polysaccharides/pharmacology*
10.Herbal Textual Research on Dendrobii Caulis in Famous Classical Formulas
Ju-run ZHAO ; Jia-chen ZHAO ; Yi-han WANG ; Yan JIN ; Wei ZHANG ; Hua-sheng PENG ; Qiu-jie CAI ; Bing LI ; Hong-jun YANG ; Hua-min ZHANG ; Zhi-lai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):215-228
Through consulting the ancient herbal and medical books, combined with the field investigation, the name, origin, collection and processing of Dendrobium medicinal materials were researched, which provided a basis for the development of famous classical formulas containing this kind of herbs. Due to the wide distribution of D. officinale, the Dendrobium species represented by D. officinale and D. huoshanense, which are short, fleshy and rich in mucus, should be the most mainstream of Dendrobium medicinal materials in previous dynasties. Compared with Shihu, Muhu with loose texture, long and hollow is born on trees. According to the characteristic description, it should be D. nobile, D. fimbriatum and so on, of which D. nobile was the mainstream. The Chinese meaning of Jinchai was confused in the past dynasties, so it was not suitable to be treated as a plant name. The production areas of Dendrobium medicinal materials in the past dynasties have changed with the discovery of varieties, artificial cultivation and other factors. Lu'an, Anhui province, was the earliest recorded in the Han and Wei dynasties. Since the Tang and Song dynasties, it had been extended to Guangdong and Guangxi, and it was considered that "Dendrobii Caulis in Guangnan was the best". In the Ming dynasty, Sichuan and Zhejiang products were highly praised, and in the Qing dynasty, Huoshan products were highly praised. Dendrobium medicinal materials had been used as medicine by stems in all dynasties. The medicinal materials were divided into fresh products and dry products. The fresh products can be used immediately after removing the sediment from the roots. The dry products need further processing, most of them used wine as auxiliary materials for steaming, simmer to paste or decoction into medicine. D. officinale and D. huoshanense have special processing specifications since the middle of Qing dynasty, that is, "Fengdou". According to the research results, in Ganluyin, the effect of Dendrobium medicinal materials is mainly heat clearing, and D. nobile with bitter taste can be selected. The main effect of Dendrobium medicinal materials in Dihuang Yinzi is tonic, D. officinale or D. huoshanense can be selected.

Result Analysis
Print
Save
E-mail