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*

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.

Objective To detect the content of rheumatoid factor(RF)after RF-CIC dissociation using serum circulating immune complexes(CIC)dissociation technology and evaluate its diagnostic and clinical value in rheumatic arthritis(RA).Methods 55 RA patients diagnosed and treated in the 903rd Hospital of the People's Liberation Army from January 2024 to December 2024 were selected as the RA disease group,and 20 healthy individuals were selected as the control group.In addition,57 non RA pa-tients with symptoms resembling RA[patients with systemic lupus erythematosus(SLE),gout,ankylosing spondylitis(AS),osteo-arthritis,etc)]as the non RA disease group.Using CIC dissociation technology,RF content after RF-CIC dissociation was detect-ed in the serum of all three groups of study subjects,and C-reactive protein(CRP)and RF levels in all subjects were detected using a biochemical analyzer.Analyzed and compared the differences in the positive rate and levels of RF-CIC among three groups object of study.In addition,analyze and compare the correlation between RF-CIC and inflammatory index CRP.Results The positive rates of RF-CIC in the serum of RA disease group,non RA disease group,and control group were 87.27%(48/55),10.53%(6/57)and 0.0%(0/20),respectively,and the differences between the three groups was statistically significant(χ2=84.520,P<0.05).Further subgroup analysis showed that the RF-CIC positivity rate in the RF negative subgroup of RA disease patients[61.11%(11/18)]higher than that in the non RA disease group[1.92%(1/52)]and the control group[0%(0/20)],and the differ-ences were statistically significant(χ2=44.493,21.671,all P<0.05).The RF-CIC positivity rate was higher in RF positive pa-tients than in RF negative patients in the RA disease group(100%vs 61.11%),and the difference was statistically significant(χ2=16.487,P<0.05).The RF-CIC content in the serum of RF positive patients in the RA disease group was higher than that of RF negative patients[16.35(10.53,26.49)vs 3.57(2.53,3.89)],and the difference was statistically significant(Z=-4.243,P<0.05).Correlation analysis showed that the levels of CRP and RF in the serum of RA patients were positively correlated with the levels of RF-CIC(r=0.490,0.970,all P<0.05).Conclusion RF-CIC demonstrates high positivity even in RF-negative RA patients,and their levels correlate with CRP.RF-CIC shows potential as a serological indicator for early diagnosis and disease activity assess-ment in RA.

The term"heat stroke"originates from the integration of modern traditional Chinese and Western medicine.In clinical practice,the complementary advantages of the two medical systems can significantly enhance the clinical diagnosis and treatment level of heat stroke.Through comprehensively analyzes the traditional Chinese medicine(TCM)nomenclature for heat stroke,proposing that heat stroke is a type of sunstroke characterized by intense and pure yang nature,specifically referring to symptoms caused directly or indirectly by hot weather.It can be referenced under the categories of Zhongye,Shuwen,Yinshu/Yangshu,Shujue,and Shufeng for treatment.The article reviews the TCM diagnostic and therapeutic thinking for heat stroke,summarizing its etiology and pathogenesis,including summerheat directly entering the Yangming,heat entering the heart and nutrient-blood aspects,evil combined with water(post-emergency),dual injury of qi and fluid(post-mild recovery),and phlegm-stasis obstructing collaterals(post-severe recovery).Based on years of clinical experience and combining the different clinical manifestations of heat stroke with TCM's four diagnostic methods,the article proposes a treatment plan that integrates Chinese and Western medicine,combining disease differentiation with syndrome differentiation.The main syndromes summarized include high fever with spasms(Yangming heat excess syndrome),diarrhea(Yangming fu syndrome-intestinal sweating),high fever with coma(heat entering the heart-nutrient syndrome),high fever with convulsions(extreme heat generating wind syndrome),heat stroke-induced coagulopathy(heat entering the blood aspect syndrome),edema after fluid resuscitation(Taiyang water retention syndrome),recovery phase(dual injury of qi and fluid syndrome),and sequelae(phlegm-stasis obstructing collaterals syndrome).For treatment,Baihu Jia Renshen decotion combined with Zengye Chengqi decotion is used for nourishing yin and increasing fluids,relaxing tendons,and stopping spasms for Yangming heat excess syndrome;Baihu decotion combined with Zengye decotion for clearing summerheat and nourishing yin for Yangming fu syndrome-intestinal sweating;Qingying decotion for clearing the nutrient aspect and cooling blood,penetrating heat,and nourishing yin for heat entering the heart-nutrient syndrome;Lingjiao Gouteng decotion for clearing heat and cooling the liver,extinguishing wind,and calming spasms for extreme heat generating wind syndrome;Wuling powder for draining and eliminating water retention for Taiyang water retention syndrome;Wang's Qing Shu Yiqi decotion for clearing summerheat and reducing fever,benefiting qi,and generating fluids for dual injury of qi and fluid syndrome;and Sanjia powder for clearing residual heat,resolving phlegm,and removing stasis from collaterals for phlegm-stasis obstructing collaterals syndrome.Starting from TCM theory and linking it with practice,the article combines Western disease differentiation with TCM syndrome differentiation,aiming to provide new ideas for the clinical treatment of heat stroke.

China's vast territory has experienced significant climate change trends in recent years,characterized by reduced regional temperature differences and prolonged high-temperature durations.In some areas,summer temperatures can exceed 39℃.Consequently,the incidence of heat stroke has risen annually,emerging as a critical and life-threatening emergency threatening public health.Ethnomedicine,developed through long-term practice across diverse ethnic groups,has cultivated regionally tailored therapeutic approaches for heat stroke based on local climatic conditions and population-specific physiological traits,offering varied treatment options for patients in different areas.However,the absence of unified ethnic medical diagnostic and therapeutic guidelines has constrained the broader application and advancement of these practices.To leverage the unique advantages of ethnic medicine in heat stroke management and enhance clinical standardization,led by the China Medical Association of Minorities:collaborated with authoritative institutions and experts in multi-ethnic medicine.Through systematic collation of ethnic medical experiences in heat stroke prevention and treatment,the team formulated the expert consensus on multi-ethnic medical diagnosis and treatment of heat stroke(2024).This consensus synthesizes shared principles across ethnic medical systems while integrating their distinct theoretical frameworks and clinical practices,yielding scientifically rigorous,practical,and widely applicable recommendations to guide clinical interventions in traditional Chinese medicine(TCM)and ethnic medicine.While ethnic medical systems differ in their etiological and pathophysiological interpretations of heat stroke,they collectively emphasize holistic regulation and adaptive treatment strategies aligned with seasonal and geographical contexts.For instance,TCM,Zhuang medicine,Miao medicine,Mongolian medicine,and Tibetan medicine employ unique methodologies:such as harmonizing qi and blood,balancing body fluids,and dispelling dampness:to address heat stroke through comprehensive interventions.These approaches include oral formulations,external therapies,specialized acupuncture-moxibustion techniques,and herbal baths,demonstrating rich clinical value.The establishment of this consensus lays a foundational framework for the standardized application of ethnic medicine in heat stroke prevention and treatment.It provides innovative insights and practical evidence for optimizing integrated rescue protocols and advancing the evidence-based integration of traditional and modern medical practices.

Objective:To visually analyze the research hotspots and development trends of traditional Chinese medicine (TCM) treatment for hypertension combined with anxiety by CiteSpace 6.4.R1 software over the past decade.Methods:The Chinese literatures on the treatment of hypertension combined with anxiety by TCM published between February 2015 and February 2025 were retrieved from CNKI, Wanfang database and VIP database.Visualization analysis was conducted using CiteSpace 6.4.R1 software to visualize the keywords, authors, and author institutions of literatures.Results:A total of 321 articles were included, showing a fluctuating upward publication trend with a peak of 42 articles in 2023. The author's co-occurrence analysis found that the core research team had not yet been formed. Shandong University of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Beijing University of Chinese Medicine, and Nanjing University of Chinese Medicine were the main research institutions. Keyword co-occurrence analysis, keyword clustering analysis, and keyword timeline chart showed that the research field mainly focused on symptom improvement, syndrome differentiation, and treatment methods.Conclusion:In the past decade, there has been an increasing amount of researches on the TCM treatment for hypertension combined with anxiety, with clinical studies remaining research hotspots. In the future, research on TCM treatment for hypertension combined with anxiety should strengthen cooperation among research institutions, form representative core research teams, and further enrich research methods.

BACKGROUND:Synovitis is involved in all stages of osteoarthritis and is a key factor contributing to the development of osteoarthritis.Studies have shown that circular RNA(circRNA)plays an important role in the proliferation,apoptosis and extracellular matrix degradation of synovial cells and chondrocytes.OBJECTIVE:To observe the effects of circRNA SEC24A on the interleukin-1β-induced proliferation,apoptosis,and expression of inflammatory factors in human synovial fibroblasts.METHODS:Human synovial fibroblasts were divided into four groups,including control group,interleukin-1β group,empty vector group,and sh-circSEC24A group.Except for the control group,the other three groups were induced with 10 ng/mL interleukin-1β for 24 hours to establish inflammatory cell models;the empty vector group and sh-circSEC24A group were infected with empty vector virus and lentiviral vector knocking down circSEC24A.CCK-8 assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.ELISA was used to detect the levels of matrix metalloproteinase-9,matrix metalloproteinase-13,interleukin-6,and tumor necrosis factor-α in cell supernatant.Western blot assay was used to detect the relative expression levels of Bax,Bcl-2,matrix metalloproteinase-9,matrix metalloproteinase-13,casepase3,cleaved-casepase3,casepase8,and cleaved-casepase8 proteins in cells.RESULTS AND CONCLUSION:(1)qRT-PCR results showed that compared with the normal group,the expression of circSEC24A in human synovial fibroblasts induced by interleukin 1β was significantly up-regulated.(2)The absorbance value of cells in the sh-circSEC24A group detected by CCK-8 assay was significantly higher than that of interleukin 1β group and empty vector group(P＜0.05).The apoptosis rate of sh-circSEC24A group detected by flow cytometry was significantly lower than that of interleukin 1β group and empty vector group(P＜0.05).(3)The levels of tumor necrosis factor α and interleukin 6 in the supernatant of human synovial fibroblasts in the sh-circSEC24A group detected by ELISA were significantly lower than those in the interleukin 1β group and the empty vector group(P＜0.01,P＜0.001).(4)Western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the expression of the pro-apoptotic factor Bax protein in the sh-circSEC24A group significantly decreased,and the expression of the anti-apoptotic factor Bcl-2 protein increased significantly(P＜0.05);apoptosis and related activating factors cleaved-casepase3 and cleaved-casepase8 protein expressions were both reduced(P＜0.05).(5)ELISA and western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the sh-circSEC24A group had lower levels of matrix metalloproteinase 9 and matrix metalloproteinase 13 protein(P＜0.05).These findings indicated that the expression of circSEC24A was abnormally increased in human synovial fibroblasts induced by interleukin 1β.Knocking down circSEC24A expression could promote the proliferation of human synovial fibroblasts and inhibit apoptosis,inflammatory factor release,and extracellular matrix degradation,suggesting that circSEC24A may be an important intervention target for early osteoarthritis.

BACKGROUND:Synovitis is involved in all stages of osteoarthritis and is a key factor contributing to the development of osteoarthritis.Studies have shown that circular RNA(circRNA)plays an important role in the proliferation,apoptosis and extracellular matrix degradation of synovial cells and chondrocytes.OBJECTIVE:To observe the effects of circRNA SEC24A on the interleukin-1β-induced proliferation,apoptosis,and expression of inflammatory factors in human synovial fibroblasts.METHODS:Human synovial fibroblasts were divided into four groups,including control group,interleukin-1β group,empty vector group,and sh-circSEC24A group.Except for the control group,the other three groups were induced with 10 ng/mL interleukin-1β for 24 hours to establish inflammatory cell models;the empty vector group and sh-circSEC24A group were infected with empty vector virus and lentiviral vector knocking down circSEC24A.CCK-8 assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.ELISA was used to detect the levels of matrix metalloproteinase-9,matrix metalloproteinase-13,interleukin-6,and tumor necrosis factor-α in cell supernatant.Western blot assay was used to detect the relative expression levels of Bax,Bcl-2,matrix metalloproteinase-9,matrix metalloproteinase-13,casepase3,cleaved-casepase3,casepase8,and cleaved-casepase8 proteins in cells.RESULTS AND CONCLUSION:(1)qRT-PCR results showed that compared with the normal group,the expression of circSEC24A in human synovial fibroblasts induced by interleukin 1β was significantly up-regulated.(2)The absorbance value of cells in the sh-circSEC24A group detected by CCK-8 assay was significantly higher than that of interleukin 1β group and empty vector group(P＜0.05).The apoptosis rate of sh-circSEC24A group detected by flow cytometry was significantly lower than that of interleukin 1β group and empty vector group(P＜0.05).(3)The levels of tumor necrosis factor α and interleukin 6 in the supernatant of human synovial fibroblasts in the sh-circSEC24A group detected by ELISA were significantly lower than those in the interleukin 1β group and the empty vector group(P＜0.01,P＜0.001).(4)Western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the expression of the pro-apoptotic factor Bax protein in the sh-circSEC24A group significantly decreased,and the expression of the anti-apoptotic factor Bcl-2 protein increased significantly(P＜0.05);apoptosis and related activating factors cleaved-casepase3 and cleaved-casepase8 protein expressions were both reduced(P＜0.05).(5)ELISA and western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the sh-circSEC24A group had lower levels of matrix metalloproteinase 9 and matrix metalloproteinase 13 protein(P＜0.05).These findings indicated that the expression of circSEC24A was abnormally increased in human synovial fibroblasts induced by interleukin 1β.Knocking down circSEC24A expression could promote the proliferation of human synovial fibroblasts and inhibit apoptosis,inflammatory factor release,and extracellular matrix degradation,suggesting that circSEC24A may be an important intervention target for early osteoarthritis.

Objective:To visually analyze the research hotspots and development trends of traditional Chinese medicine (TCM) treatment for hypertension combined with anxiety by CiteSpace 6.4.R1 software over the past decade.Methods:The Chinese literatures on the treatment of hypertension combined with anxiety by TCM published between February 2015 and February 2025 were retrieved from CNKI, Wanfang database and VIP database.Visualization analysis was conducted using CiteSpace 6.4.R1 software to visualize the keywords, authors, and author institutions of literatures.Results:A total of 321 articles were included, showing a fluctuating upward publication trend with a peak of 42 articles in 2023. The author's co-occurrence analysis found that the core research team had not yet been formed. Shandong University of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Beijing University of Chinese Medicine, and Nanjing University of Chinese Medicine were the main research institutions. Keyword co-occurrence analysis, keyword clustering analysis, and keyword timeline chart showed that the research field mainly focused on symptom improvement, syndrome differentiation, and treatment methods.Conclusion:In the past decade, there has been an increasing amount of researches on the TCM treatment for hypertension combined with anxiety, with clinical studies remaining research hotspots. In the future, research on TCM treatment for hypertension combined with anxiety should strengthen cooperation among research institutions, form representative core research teams, and further enrich research methods.