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.Circular RNAs are involved in the pathogenesis of osteoarthritis through intracellular mechanisms
Lijun ZHOU ; Keyuan ZHANG ; Xi WANG ; Li YU ; Feihu XU ; Hong DING ; Hairong MA
Chinese Journal of Tissue Engineering Research 2024;28(35):5716-5722
BACKGROUND:Currently,there is no drug that can completely cure osteoarthritis and its pathogenesis is still unclear.Circular RNAs(circRNAs)are differentially expressed in patients with osteoarthritis and are closely associated with various pathological processes in osteoarthritis.circRNAs play an important role in various physiological and pathological processes,such as chondrocyte homeostasis,extracellular matrix formation,and inflammatory response. OBJECTIVE:To mainly review the effects of circRNAs on pathological factors related to osteoarthritis,as well as the types and expression levels of circRNAs in osteoarthritis. METHODS:Related articles published from 1976 to August 2023 were retrieved from CNKI,WanFang,VIP,PubMed,Medline,Web of Science and Elsevier databases.The keywords were"osteoarthritis,circular RNA,non-coding RNA,synovial tissue,chondrocytes"in Chinese and English,respectively.All the relevant articles were screened,summarized,analyzed,and finally 69 papers were included in the review. RESULTS AND CONCLUSION:circRNAs are non-coding RNAs widely found in eukaryotic cells,with covalently closed continuous loop structure,but with no 5'hat structure and 3'poly A tail,which are involved in multi-gene and multi-target regulatory networks and cannot be degraded by nucleic acid exonucleases(RNase R).circRNAs have a high abundance,high conservativeness and stability,and cell and tissue specificity.circRNAs have biological functions such as acting as molecular sponges for miRNAs,regulating linear RNA transcription and RNA shearing,interacting with RNA-bound proteins,and translating proteins.circRNAs regulate chondrocyte apoptosis and proliferation,degradation of cartilage extracellular matrix,and inflammation and other physiopathologic processes.circRNAs are expected to become biomarkers and potential therapeutic targets for clinical diagnosis and prognosis of osteoarthritis,and may become a new strategy for clinical treatment of osteoarthritis in the future.
5.A Study on the Relationship between Primary Indicators in Performance Assessment of Tertiary Public Hospitals
Feihu SHEN ; Xiaohe WANG ; Doudou YANG
Chinese Health Economics 2024;43(1):63-66
Objective:To explore the relationships among 4 primary indicators in the performance assessment and evaluation system of tertiary public hospitals.Methods:A questionnaire survey was employed to collect data on healthcare professionals'perceptions of the rationality of performance evaluation indicators.Structural equation modeling(SEM)and Amos 21.0 Statistical Software were utilized for data analysis,with the mediation effects tested using the Bootstrap method.Results:A total of 826 valid questionnaires were obtained.Medical quality,operational efficiency,and sustainable development had a positive impact on satisfaction.Operational efficiency and sustainable development played a chain-mediated role in the process of medical quality influencing satisfaction evaluation,namely"medical quality → operational efficiency → sustainable development → satisfaction".Conclusion:It helps to flexibly apply and deepen the integration of knowledge in the field of enterprise management into the field of hospital management,helps hospitals to scientifically formulate internal performance evaluation programs under the premise of limited resources,and provides new ideas for the country to optimize the performance appraisal index system of tertiary public hospitals.
6.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
7.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.
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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