1.Pathological Roles and Regulatory Mechanisms of Macrophage Polarization Imbalance in Steroid-associated Osteonecrosis of The Femoral Head
Hui LI ; Duo-Xian WANG ; Wei-Chuang LIU ; Bo-Bo TUO ; Xin CHEN ; Jian-Jun LIU
Progress in Biochemistry and Biophysics 2026;53(9):2392-2401
Steroid-associated osteonecrosis of the femoral head (SANFH) is a progressive osteoarticular disorder associated with prolonged or high-dose glucocorticoid exposure. Its development involves local ischemia, oxidative stress, dysregulated bone metabolism, and disruption of the osteoimmune microenvironment. Macrophages exhibit marked phenotypic plasticity, and their polarization is essential for maintaining the dynamic balance among inflammation, angiogenesis, and bone remodeling. Persistent glucocorticoid stimulation, hypoxia, excessive reactive oxygen species, and damage-associated signals released from necrotic tissues can shift macrophages toward a pro-inflammatory phenotype. Classically activated macrophages (M1 macrophages) predominantly mediate inflammatory responses. By releasing tumor necrosis factor-α, interleukin-1β, interleukin-6, and other mediators, promoting osteoclast activation, suppressing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and impairing vascular endothelial function, M1 macrophages accelerate trabecular destruction and expansion of the necrotic lesion. In contrast, alternatively activated macrophages (M2 macrophages) contribute to inflammation resolution, neovascularization, osteogenic repair, and tissue remodeling, thereby supporting regeneration within the necrotic region. Macrophage-derived exosomes further influence disease progression through intercellular communication. Exosomes from different macrophage phenotypes can differentially regulate adipogenic differentiation, neutrophil extracellular trap formation, and endothelial phenotypic transition, thereby affecting the repair capacity of the necrotic area. These findings indicate that macrophage polarization shapes the local microenvironment not only through soluble mediators but also through vesicle-mediated communication with BMSCs, neutrophils, endothelial cells, and other cell populations. At the molecular level, the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3) inflammasome, nuclear factor kappa B (NF‑κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways jointly regulate macrophage polarization and its downstream osteoimmune effects. Dysregulation of these pathways may sustain inflammatory activation, aggravate oxidative and vascular injury, inhibit osteogenesis, and impair tissue repair. NLRP3 inflammasome activation links danger signals and oxidative stress to inflammatory cytokine maturation and pyroptotic injury; NF-κB signaling promotes pro-inflammatory gene transcription and M1 polarization; JAK/STAT signaling participates in the balance between inflammatory and reparative macrophage programs; and PI3K/Akt/mTOR signaling regulates cellular metabolism, survival, autophagy, and regeneration. Notably, the biological effects of PI3K/Akt/mTOR signaling are cell-type dependent, and Akt-mediated repair signaling should be distinguished from mTOR-related autophagy regulation. The pathological significance of macrophage polarization in SANFH is not determined simply by an increase or decrease in a single phenotype. Rather, disease progression appears to result from an imbalance between persistent pro-inflammatory activity and insufficient reparative responses at different stages of the disease. Such an imbalance disrupts the coordinated coupling of inflammation resolution, vascular regeneration, and bone remodeling, ultimately contributing to structural deterioration of the femoral head. This review summarizes the pathological roles, signaling regulation, and exosome-mediated intercellular communication associated with macrophage polarization imbalance in SANFH. A more precise understanding of these mechanisms may clarify the osteoimmune basis of SANFH and support the development of macrophage-targeted interventions. However, most available evidence is derived from cellular and animal studies, and the temporal evolution of macrophage phenotypes in patients remains insufficiently characterized. Therapeutic strategies should therefore move beyond the simple suppression of M1 macrophages or enhancement of M2 macrophages and instead aim to restore a stage-appropriate balance between inflammatory control and tissue repair while promoting angiogenesis and bone reconstruction.
2.Efficacy,safety,and cost-effectiveness of berberine-based quadruple therapy for Helicobacter pylori infection in treatment-naive patients:a single-center randomized controlled study
Dan-Dan LIU ; Jiang-Shan SUN ; Yu-Jie TUO ; Yong YU ; Chun-Yan ZHANG ; Han-Chen MIN ; Xiao-Mei ZHANG
Medical Journal of Chinese People's Liberation Army 2025;50(11):1414-1418
Objective To evaluate the efficacy,safety,and cost-effectiveness of berberine-based quadruple therapy vs.the clarithromycin-based quadruple therapy for Helicobacter pylori(H.pylori)eradication in treatment-na?ve patients.Methods This was a single-center,prospective,open-label randomized controlled trial.A total of 404 treatment-naive patients with H.pylori infection who visited the Outpatient Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital from September 2021 to May 2024 were enrolled.The patients were randomly assigned in a 1:1 ratio to two groups:berberine quadruple therapy group(berberine+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202)and clarithromycin quadruple therapy group(clarithromycin+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202).Both groups received a 14-day treatment course.The H.pylori eradication rate,incidence of adverse reactions,medication compliance,and treatment costs were compared between the two groups.Results By intention-to-treat(ITT)analysis,eradication rate did not differ significantly between the two groups[89.1%(180/202)in berberine quadruple therapy group vs.89.6%(181/202)in clarithromycin quadruple therapy group,P=0.872].The per-protocol(PP)analysis also showed no significant difference in the eradication rate between the two groups[90.4%(179/198)vs.91.3%(178/195),P=0.763].The incidence of adverse reactions in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group[18.2%(36/198)vs.38.5%(75/195),P<0.001].Specifically,the incidence of taste disturbance in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group(3.0%vs.15.4%,P<0.001).There was no statistically significant difference in medication compliance between the two groups[98.5%(195/198)in berberine quadruple therapy group vs.97.9%(191/195)in clarithromycin quadruple therapy group,P=0.688].The fixed direct medical cost per patient was significantly lower in berberine quadruple therapy group than that in clarithromycin quadruple therapy group(402.08 yuan vs.693.94 yuan).Conclusions The berberine-based quadruple therapy is as effective as traditional clarithromycin-based quadruple therapy for eradicating H.pylori,with the advantages of a lower incidence of adverse reactions and lower cost.It represents a safe,effective,and economical treatment option worthy of further promotion and application.
3.Transcutaneous auricular vagus nerve stimulation regulates functional connectivity of thalamic subregions in patients with premenstrual syndrome
Ruijing SUN ; Yinqi LAI ; Ya CHEN ; Yuejuan WU ; Zhen LIU ; Qingping ZHANG ; Ziyan LAI ; Gaoxiong DUAN ; Yan ZHANG ; Shanshan LI ; Yuanyuan OU ; Sijing TUO ; Hui ZHOU ; Rongcai WU ; Zhizhong CHEN ; Demao DENG
Chinese Journal of Radiology 2025;59(12):1384-1392
Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.
4.Research on the implementation effect evaluation of Warning Signs for Occupational Hazards in the Workplace (GBZ 158-2003)
Tuo LIU ; Wenjie LI ; Xiaoshuang XIE ; Yang LU ; Peng QIN ; Qiuhong ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(5):392-396
To summarize the problems and improvement suggestions in the implementation of GBZ158, the focus groups interview was used to interview industry experts from CDC, Occupational disease prevention and control hospital institutes, employers, third d dd鄄party technical service institutions and universities, and extract their opinions on the problems and improvement suggestions in the implementation of the standard. The operability of GBZ 158 is not strong, and there is a certain overlap with the signs in the fields of firefighting, safety and other fields. It urgently needs to be modified to comply with the reality of occupational health management in China. There are many and concentrated revision opinions on "6. Notification Cards for Occupational Hazards of Toxic Substance in Workplaces" and "7. Setting of Warning Signs in Workplaces with Toxic Substances". It is concluded that Some technical indicators of GBZ 158 have not been according with the current actual work of occupational health, and need to be revised and improved urgently, which includes enhancing the coordination with standards in the fields of firefighting and safety, supplementing normative reference documents, clarifying the setting conditions, scope of use, and application examples of warning signs of occupational hazards.
5.Comparison research on occupational exposure limits of nickle and its compounds between China and foreign countries
Yang LU ; Tuo LIU ; Yuling ZHU ; Wenjie LI ; Qiuhong ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(5):357-364
Objective:To study and compare the occupational exposure limits (OELs) of nickle and its compounds between China and foreign countries, providing scientific basis for the OEL revision of nickel and its compounds in China.Methods:From July to September 2024, Literature, OEL and related technical documents on nickel and its compounds were searched and sorted systematically at home and abroad, the main contents and technical points of OEL were extracted, and comparative analysis were conducted.Results:The earliest OELs of nickel and its compound introduced to China was maximum allowable concentration (MAC) of nickel carbonyl, and the current effective standard China was occupational exposure limits for hazardous agents in the workplace-part 1: chemical hazardous agents (GBZ 2.1-2019), covering nickel and inorganic compounds and nickel carbonyl. The former was further divided into nickel metal and insoluble compounds, and soluble nickel compounds. Based solely on the OELs of nickel and its compounds, China was relatively lower compared to developed countries such as the United States. There were significant differences in the OEL of different types of nickel and its compounds among different countries, but the OELs in China and the United Kingdom (UK) Health and Safety Executive (HSE) were basically consistent. The European Union, the United States American Conference of Governmental Industrial Hygienists (ACGIH), South Africa etal classified nickel and its compounds into respirable and inhalable based on particle size. GBZ 2.1-2019 in China labeled nickel compounds and nickel carbonyl as G1 (carcinogenic to humans), while ACGIH and National Institute for Occupational Safety and Health (NIOSH) in the United States, HSE in the UK, Australia, South Africa also labeled one or several different types of nickel and its compounds as carcinogenic.Conclusion:Based on the OELs of nickel and its compounds, China is at a relatively loose level. It is suggested to explore the possibility of future revision, considering various adverse health effects. It is suggested to conduct basic research on fibrosis induced by nickel and its compounds, providing scientific basis for revising OELs.
6.Implementation evaluation and analysis of occupational exposure limits for hazardous agents in the workplace Part 1: Chemical hazardous agents (GBZ 2.1-2019)
Wenjie LI ; Tao LI ; Tuo LIU ; Chen YU ; Dan WANG ; Yang LU ; Xiaoshuang XIE ; Peng QIN ; Kaining TIAN ; Qiuhong ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(5):364-367
Objective:By systematically evaluate the implementation of GBZ 2.1, so as to provide technical basis for the future revisions of this standard.Methods:From May to October 2023, Based on the pre survey questionnaire, the semi-structured interview method was used to interviews with experts from CDC, Occupational disease prevention and control hospital institutes, employers, occupational hygiene technical service intermediaries and universities, and the inductive method was used to extract the topics and relevant suggestions.Results:Generally, GBZ 2.1 is scientific, practical, progressiveness and operable. There are still some issues such as OELs overlapping and the correspondence between Chinese and English names. The outstanding problem is the coordination with other standard contents.Conclusion:The technical indicators in GBZ 2.1 could adapt to the needs of current practical work. The coordination between standards needs to be clarified, and the new recommended content needs further promotion and exploration on how to implement it.
7.Shenlian Extract Protects against Ultrafine Particulate Matter-Aggravated Myocardial Ischemic Injury by Inhibiting Inflammation and Cell Apoptosis.
Shui Qing QU ; Yan LIANG ; Shuo Qiu DENG ; Yu LI ; Yue DAI ; Cheng Cheng LIU ; Tuo LIU ; Lu Qi WANG ; Li Na CHEN ; Yu Jie LI
Biomedical and Environmental Sciences 2025;38(2):206-218
OBJECTIVE:
Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis.
METHODS:
We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro.
RESULTS:
SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells.
CONCLUSION
Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals
;
Apoptosis/drug effects*
;
Particulate Matter/adverse effects*
;
Mice
;
Male
;
Inflammation/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Mice, Inbred C57BL
;
Myocardial Ischemia/drug therapy*
;
Cell Line
8.Visual analysis for published literature in the Chinese Journal of Industrial Hygiene and Occupational Diseases from 1983 to 2023
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(8):580-585
Objective:To conduct a visual analysis of the papers published in the Chinese Journal of Industrial Hygiene and Occupational Diseases since its inception, and to understand the current situation and development trends in the field of occupational health and occupational diseases.Methods:A total of 9894 papers published in the Chinese Journal of Industrial Hygiene and Occupational Diseases from January 1, 1983 to December 31, 2023 were retrieved from China National Knowledge Infrastructure (CNKI) in February 2024. Non-academic literature was screened and excluded. Excel 2010 and SPSS 24.0 were used to analyze the annual publication situation. Visualization software CiteSpace V6.2.R7 was used to conduct co-occurrence analysis, cluster analysis and emergence analysis for keywords and to make knowledge graph.Results:A total of 9381 literatures were included. From 1983 to 2023, the annual publication volume in Chinese Journal of Industrial Hygiene and Occupational Diseases showed an M-shaped fluctuation, with the largest number of literatures published in 2010 (351 literatures). The co-occurrence analysis of keywords showed that the occurrence frequency of keywords such as poisoning, pneumoconiosis, occupational exposure and silicosis was high. By cluster analysis, the literature keywords were summarized into 10 clusters of pneumoconiosis, noise, stress, microwave, paraquat, poisoning, chromatography, polymorphism, silicosis, and yellow phosphorus. The emergence analysis showed that occupational stress, influencing factors, occupational health, occupational diseases and pneumoconiosis were the top 5 keywords of emergence intensity, while noise and hearing loss were the keywords of greater emergence intensity after 2020.Conclusion:The contents of the studies on pneumoconiosis and poisoning published in the Chinese Journal of Industrial Hygiene and Occupational Diseases are relatively stable, while occupational stress and noise have become research hot spots in recent years. It is suggested to strengthen the cross and integration of multi-disciplines in order to promote the development of occupational health and occupational disease fields.
9.Characteristic analysis of the determination standards for toxic substances in the workplace in China
Xiaoshuang XIE ; Tuo LIU ; Yang LU ; Qiuhong ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(5):353-357
Objective:To analyze the characteristics of toxic substances determination standards in workplaces in China, in order to provide basis for further development of national occupational health standards.Methods:In November 2023, Used descriptive analysis methods, conduct a characteristic analysis of the toxic substance determination standards for workplaces in China issued between 2004 and 2024, including the first drafting situation, standard formulation/revision situation, standard determination methods types, and method performance indicators.Results:The The first drafting unit in the GBZ/T 160 and GBZ/T 300 standards that have been issued is mainly composed of disease prevention and control centers (154, accounting for 60.6%) and the hospital of Occupational disease prevention and control (154, accounting for 60.6%). The regional distribution is North China (65 items, accounting for 25.6%), East China (60 items, accounting for 23.7%), and South China (51 items, accounting for 20.2%). 93.1% of the standards were published between 2004 and 2017; Covering 671 measurement methods.The method types are gas chromatography (367, 54.7%), spectrophotometry (98, 14.6%), inductively coupled plasma mass spectrometry (54, 8.0%), etc. The missing items of standard performance indexes mainly focus on penetration capacity, recovery rate and detection limit. The missing items of penetration capacity and recovery rate are mainly distributed in gas chromatography methods; The missing detection limits and minimum detection concentrations are mainly distributed in spectrophotometry and gas chromatography method.Conclusion:Suggest accelerating the update speed of toxic substance determination standards in the workplace, supplementing the supporting determination methods in GBZ 2.1 standard, focusing on solving common problems in existing standards, gradually improving the standards for missing performance indicators, and gradually carrying out national standard transformation in a hierarchical and phased manner for local or group standards with good practical applications.
10.APR-246 combined with irradiation can enhance anti-tumor immune response against mouse 4T1 breast cancer cells
Feifei MA ; Tuo LI ; Shujuan LU ; Jianguo LI ; Ning WANG ; Huanteng ZHANG ; Jiebing GUAN ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2025;45(4):275-281
Objective:To explore the effects of combining APR-246 with irradiation for enhancing anti-tumor immune response against 4T1 breast cancer cells, and to develop multiple tumor treatment strategies.Methods:The control group, APR-246 group, irradiation group and irradiation combined APR-246 group were used both in the cell experiment and tumor-bearing mice experiment. The inhibitory effect of APR-246 on the proliferation of 4T1 cells was assessed by using Cell Counting Kit-8. The effect of APR-246 with irradiation on the survival rate of 4T1 cells using clone formation assay was measured. The levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in tumor cells using a 2’, 7’-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and a lipid peroxidation sensor, the tumor inhibition rates of different groups of tumor bearing mice were compared, and the proportions of CD4+ and CD8+ T cells and the ratio of M1/M2 macrophages were determined in the tumor microenvironment by flow cytometry.Results:Compared with irradiation group, 2, 4, 6 Gy irradiation combined APR-246 group significantly reduced the survival rates of 4T1 cells ( t = 2.89, 4.15, 2.62, P < 0.05), the 6 Gy irradiation combined APR-246 group significantly increased the levels of ROS ( t = 16.95, P < 0.05) and LPO ( t = 6.09, P < 0.05) in 4T1 cells, and significantly increased the apoptosis rate of 4T1 cells ( t = 10.99, P < 0.05). Meanwhile, from the 16 th day of tumor inoculation, the 10 Gy irradiation combined APR-246 group showed significantly inhibited tumor growth ( t = 2.38-2.91, P < 0.05) and significantly increased proportions of CD4+ and CD8+ T cells ( t = 9.96, 6.28, P < 0.05) and M1/M2 ratio ( t = 15.30, P < 0.05) in tumor tissues. Conclusions:APR-246 combined with irradiation can effectively increase ROS and LPO levels in 4T1 cells, promote tumor cell apoptosis, and induce anti-tumor immune response, thus potentially inhibiting the growth of 4T1 cells.

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