1.Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.
Chenwei JIANG ; Minglu TANG ; Yun SU ; Junjie XIE ; Qi SHANG ; Mingmei GUO ; Xiaoran AN ; Longfei LIN ; Ruibin WANG ; Qian HUANG ; Guangji ZHANG ; Hui LI ; Feihu WANG
Acta Pharmaceutica Sinica B 2025;15(6):2845-2866
Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.
3.G protein-coupled estrogen receptor alleviates lung injury in mice with exertional heat stroke by inhibiting ferroptosis.
Ziwei HAN ; Jiansong GUO ; Xiaochen WANG ; Zhi DAI ; Chao LIU ; Feihu ZHOU
Chinese Critical Care Medicine 2025;37(3):268-274
OBJECTIVE:
To investigate whether the G protein-coupled estrogen receptor (GPER) can attenuates acute lung injury in mice with exertional heat stroke (EHS) by inhibiting ferroptosis.
METHODS:
Sixty SPF-grade male C57BL/6 mice were randomly divided into four groups: normal control group (control group), EHS model group (EHS group), dimethyl sulfoxide (DMSO) solvent group (EHS+DMSO group), and GPER-specific agonist G1 group (EHS+G1 group), with 15 mice in each group. All mice underwent 14 days of adaptive training at 24-26 centigrade before modeling, and the EHS model was established using a high-temperature treadmill device. After successful modeling, the mice were allowed to cool naturally at room temperature. In the EHS+G1 group, 40 μg/kg of the GPER-specific agonist G1 was slowly injected intraperitoneally immediately after modeling. In the EHS+DMSO group, 40 μg/kg of DMSO was slowly injected intraperitoneally immediately after modeling. The control group received no treatment. Five hours after modeling, abdominal aortic blood was collected, and lung tissues were harvested after euthanasia. The lung coefficient was calculated to evaluate lung injury. Lung histopathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and a lung histopathological score was assigned. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Fe2+ in lung tissue. Immunofluorescence was used to detect the expression of glutathione peroxidase 4 (GPX4). Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GPX4, ferroportin 1 (FPN1), and ferritin heavy chain 1 (FTH1). Western blotting was performed to detect the protein expression of GPX4, FPN1, and FTH1.
RESULTS:
Compared with the control group, the lung coefficient and lung histopathological score were significantly increased in the EHS group. HE staining showed significant thickening and unevenness of the alveolar septa and alveolar walls, partial alveolar collapse, and extensive erythrocyte, inflammatory cell, and plasma-like material extravasation in the alveolar spaces. Serum levels of TNF-α, IL-1β, MDA, and Fe2+ were significantly elevated. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue. Western blotting and RT-PCR showed significantly reduced protein and mRNA expression of GPX4, FPN1, and FTH1 in lung tissue. Compared with the EHS group, the EHS+G1 group showed a significant reduction in lung coefficient and lung histopathological score [lung coefficient (mg/g): 3.9±0.1 vs. 4.6±0.3, lung histopathological score: 4.2±0.2 vs. 6.9±0.2, both P < 0.05]. HE staining revealed reduced severity of lung tissue fluid extravasation, inflammatory infiltration, decreased hemorrhage, and less severe alveolar structural damage. Serum levels of TNF-α, IL-1β, MDA, and Fe2+ were significantly reduced [TNF-α (ng/L): 44.3±0.2 vs. 64.6±0.3, IL-1β (ng/L): 69.3±0.4 vs. 97.8±0.2, MDA (nmol/L): 2.8±0.3 vs. 3.6±0.5, Fe2+ (nmol/L): 0.021±0.004 vs. 0.028±0.004, all P < 0.05]. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue (fluorescence intensity: 35.53±2.41 vs. 16.45±0.31, P < 0.05). RT-PCR and Western blotting showed significantly increased mRNA and protein expression of GPX4, FPN1, and FTH1 in lung tissue [mRNA expression: GPX4 mRNA (2-ΔΔCt): 0.44±0.05 vs. 0.09±0.01, FPN1 mRNA (2-ΔΔCt): 0.77±0.17 vs. 0.42±0.14, FTH1 mRNA (2-ΔΔCt): 0.75±0.04 vs. 0.58±0.01; protein expression: GPX4/β-actin: 0.96±0.11 vs. 0.24±0.04, FPN1/β-actin: 1.26±0.21 vs. 0.44±0.14, FTH1/β-actin: 0.27±0.12 vs. 0.15±0.07; all P < 0.05]. However, there were no statistically significant differences in any of the above indicators between the EHS+DMSO group and the EHS group.
CONCLUSION
Activation of GPER can attenuate EHS-related lung injury in mice, and its mechanism may be related to the activation of the GPX4 signaling pathway and inhibition of ferroptosis.
Animals
;
Mice, Inbred C57BL
;
Male
;
Mice
;
Heat Stroke/metabolism*
;
Receptors, G-Protein-Coupled
;
Ferroptosis
;
Receptors, Estrogen
;
Acute Lung Injury/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Interleukin-1beta/metabolism*
;
Lung Injury
;
Lung/metabolism*
4.Obstructive sleep apnea exacerbates cognitive impairment after stroke and the diagnostic value of serum BDNF and Tau protein
Dongmei ZHAO ; Feihu CAO ; Libo WANG ; Jun HUANG ; Yuxin DU ; Qian LIU
Basic & Clinical Medicine 2025;45(9):1195-1199
Objective To explore the impact of obstructive sleep apnea(OSA)on cognitive impairment in post-stroke patients,to explore its underlying mechanism and to evaluate potential diagnostic value by dynamically moni-toring the level of brain-derived neurotrophic factor(BDNF)and Tau protein in serum.Methods Totally 96 stroke patients admitted to Mianyang third People's Hospital from February 2022 to June 2024 were selected.They were divided into the groups complicated with OSA and control one without OSA following up of neuropsychological scales for 1 week,1 month,3 months,and 6 months after stroke for evaluating cognitive function.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the level of BDNF and Tau protein in serum.The correlation of test results and the degree of cognitive impairment as well as their diagnostic value were analyzed.Results The AHI in the OSA group was significantly higher than that of control group,while LSaO2 and MSaO2 were significantly lower in the OSA group(P<0.05).One week and 1,3,6 month months after the onset of the disease,the MMSE and MoCA scores in the OSA group were significantly lower than those in the control group,BDNF level was signifi-cantly lower while Tau protein level was significantly higher as compare to those in control group(P<0.05).Pear-son correlation analysis showed that the serum BDNF level was positively correlated with both MMSE score(r=0.654,P<0.001)and MoCA score(r=0.689,P<0.001).However,the serum Tau protein level was nega-tively correlated with both MMSE score(r=-0.623,P<0.001)and MoCA score(r=-0.667,P<0.001).The ar-ea under the curve(AUC)of the combined detection of BDNF and Tau protein was greater than that of the individ-ual detection.The diagnostic value of the combined detection of BDNF and Tau protein for cognitive impairment in post-stroke patients was greater than that of the individual detection(P<0.05).Conclusions OSA significantly exacerbates patients'cognitive impairment after stroke.Elevated serum BDNF level and decreased Tau protein level may be the underlying mechanisms of cognitive impairment.Serum BDNF and Tau protein may function as potential biomarkers for diagnosis of cognitive impairment after stroke.
5.Importance-efficacy Cognitive Analysis of Performance Evaluation Indicators for Level-3 Public Hospitals based on the IPA Model
Feihu SHEN ; Xiaohe WANG ; Huimin SONG
Chinese Hospital Management 2024;44(7):59-62
Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.
6.Influencing factors of depressive symptoms in patients with vestibular neuritis
Shuangzhi WANG ; Feihu CAO ; Liu WANG ; Jiawei HE ; Xin ZOU ; Diwen ZHANG
Sichuan Mental Health 2024;37(6):557-561
BackgroundVestibular neuritis is a common clinical acute peripheral vertigo disorder. Some patients may experience negative emotions states, leading to chronic exacerbation of vestibular neuritis and a poorer prognosis. Further research is needed to understand the psychological state of patients with vestibular neuritis and its influencing factors. ObjectiveTo explore the relationship between depressive symptoms and vestibular symptoms in patients with vestibular neuritis and its influencing factors, so as to provide references for clinical intervention. MethodsA total of 86 patients with vestibular neuritis, hospitalized in the Department of Neurology of the Third Hospital of Mianyang from June 2021 to June 2023, were included in the study. Assessments were conducted using the Hamilton Depression Scale-17 item (HAMD-17), Dizziness Assessment Rating Scale (DARS) and Dizziness Handicap Inventory (DHI). Patients were divided into depression group(n=46) and non-depression group(n=40) based on HAMD-17 score. Pearson correlation analysis was used to examine the correlation among each scale score. Binary Logistic regression was used to identify influencing factors for depressive symptoms. ResultsAmong the 86 patients, 46 (53.49%) exhibited depressive symptoms. Statistically significant differences were observed between depression group and non-depression group in terms of age, disease duration, years of education, DARS score and DHI score (t=4.512, 4.921, 2.712, 3.529, 5.471, P<0.01 ). In depression group, HAMD-17 score was positively correlated with DARS score and DHI score (r=0.345, 0.335, P<0.01). Binary Logistic regression analysis showed that age (OR=4.352, 95% CI: 1.520~12.462), disease duration(OR=3.772, 95% CI: 1.339~10.630), years of education (OR=0.074, 95% CI: 0.235~0.923), DARS score (OR=1.213, 95% CI: 0.405~3.628) and DHI score (OR=3.619, 95% CI: 1.246~10.514) were the influencing factors of depressive symptoms among patients with vestibular neuritis. ConclusionDepressive symptoms in patients with vestibular neuritis are positively correlated with vestibular symptoms. Risk factors for depressive symptoms in patients with vestibular neuritis include age, disease duration, DARS score and DHI score, while years of education serve as a protective factor.
7.Importance-efficacy Cognitive Analysis of Performance Evaluation Indicators for Level-3 Public Hospitals based on the IPA Model
Feihu SHEN ; Xiaohe WANG ; Huimin SONG
Chinese Hospital Management 2024;44(7):59-62
Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.
8.Importance-efficacy Cognitive Analysis of Performance Evaluation Indicators for Level-3 Public Hospitals based on the IPA Model
Feihu SHEN ; Xiaohe WANG ; Huimin SONG
Chinese Hospital Management 2024;44(7):59-62
Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.
9.Importance-efficacy Cognitive Analysis of Performance Evaluation Indicators for Level-3 Public Hospitals based on the IPA Model
Feihu SHEN ; Xiaohe WANG ; Huimin SONG
Chinese Hospital Management 2024;44(7):59-62
Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.
10.Importance-efficacy Cognitive Analysis of Performance Evaluation Indicators for Level-3 Public Hospitals based on the IPA Model
Feihu SHEN ; Xiaohe WANG ; Huimin SONG
Chinese Hospital Management 2024;44(7):59-62
Objective It explores the importance and effectiveness perception of 55 third-tier indicators in the cur-rent performance evaluation system.Methods From the perspective of those being assessed,it employs survey ques-tionnaires,Importance Performance Analysis(IPA),and focus group interviews to conduct research on the impor-tance and effectiveness perception.Results The overall perception of the importance and effectiveness of third-tier in-dicators is relatively high,and the performance evaluation indicator system can effectively assess the development level of level-3 public hospitals.There is a general discrepancy between the perception of importance and effective-ness.Some third-tier indicators face issues of insufficient perception of both importance and effectiveness.Conclu-sion Performance evaluation policy formulation based on the implementation of policies and after excluding the scores of indicators closely related to stakeholders can re-monitor and analyze indicators.This allows for the addition or removal of third-tier indicators,adjustment of indicator weights,optimization of indicator content,precision in mea-suring indicators,and improvement of the performance evaluation effectiveness of level-3 public hospitals.

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