1.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.
2.Research advances in methods for personal dose monitoring in interventional radiology
Xuanrong ZHANG ; Wen GUO ; Xian XUE ; Yanqiu DING
Chinese Journal of Radiological Health 2026;35(1):141-147
This paper primarily reviews the current research status of passive and active monitoring methods for interventional radiology personnel, encompassing the types and wearing positions of personal dosimeters, simulation results versus measured outcomes, and discrepancies between different simulation results. By reviewing domestic and international literature, it lists effective dose estimation formulas for single- and dual-dosimeter systems developed by various researchers worldwide. Recommendations are proposed based on the current dosimeter wearing practices among interventional radiology staff, providing reference for the formulation of relevant standards.
3.Cuscutae Semen-Lycii Fructus Improves Spermatogenesis in Rat Model of Oligoasthenozoospermia by Inhibiting Oxidative Stress-induced Blood-testis Barrier Damage via Regulating SIRT1/Nrf2 Signaling Pathway
Wen DUAN ; Xiaojing ZHANG ; Wenjie DING ; Jianning JIN ; Guoqing CHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):29-38
ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia (OAS) and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsThirty-five male SD rats were randomized into a blank group (n=7) and a modeling group (n=28). The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups: model, Cuscutae Semen-Lycii Fructus granules (3.2 g·kg-1), Cuscutae Semen-Lycii Fructus total flavonoids (0.34 g·kg-1), and L-carnitine (0.38 g·kg-1), and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase (SOD), malondialdehyde (MAD), and glutathione peroxidase (GSH-Px) in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of SIRT1, Nrf2, Occludin, zonula occludens-1 (ZO-1), connexin 43 (CX43), and β-catenin. ResultsCompared with the blank group, the model group showed decreased total sperm count and motility (P<0.05, P<0.01), obvious damage in the testicular tissue and blood-testis barrier structure, reduced score of spermatogenic function (P<0.01), declined levels of GSH-Px and SOD in the testicular tissue (P<0.05), elevated level of MDA, and down-regulated protein levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin (P<0.05, P<0.01) and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, and β-catenin in the testicular tissue (P<0.05, P<0.01). After treatment, the testicular tissue, blood-testis barrier structure, and score of spermatogenic function (P<0.01) were improved in the Cuscutae Semen-Lycii Fructus granules group, Cuscutae Semen-Lycii Fructus total flavonoids group, and L-carnitine group. Compared with the model group, the treatment groups presented lowered levels of GSH-Px and SOD (P<0.05, P<0.01), and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group (P<0.05, P<0.01). ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage, thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.
4.Cuscutae Semen-Lycii Fructus Improves Spermatogenesis in Rat Model of Oligoasthenozoospermia by Inhibiting Oxidative Stress-induced Blood-testis Barrier Damage via Regulating SIRT1/Nrf2 Signaling Pathway
Wen DUAN ; Xiaojing ZHANG ; Wenjie DING ; Jianning JIN ; Guoqing CHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):29-38
ObjectiveTo investigate the effect of the herb pair Cuscutae Semen-Lycii Fructus on oxidative stress-induced blood-testis barrier dysfunction and spermatogenesis in the rat model of oligoasthenozoospermia (OAS) and decipher the mechanism based on the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsThirty-five male SD rats were randomized into a blank group (n=7) and a modeling group (n=28). The OAS model was established by gavage of hydrocortisone aqueous solution combined with single factor electrical stimulation. The modeled rats were randomly assigned into the following groups: model, Cuscutae Semen-Lycii Fructus granules (3.2 g·kg-1), Cuscutae Semen-Lycii Fructus total flavonoids (0.34 g·kg-1), and L-carnitine (0.38 g·kg-1), and treated for 4 weeks. The sperm quality of rats was assessed by an automatic sperm analyzer. The levels of superoxide dismutase (SOD), malondialdehyde (MAD), and glutathione peroxidase (GSH-Px) in the testicular tissue were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the pathological changes in the testicular tissue and score the spermatogenic function. Transmission electron microscopy was employed to observe the ultrastructural changes of Sertoli cells. Western blot and Real-time PCR were employed to determine the protein and mRNA levels, respectively, of SIRT1, Nrf2, Occludin, zonula occludens-1 (ZO-1), connexin 43 (CX43), and β-catenin. ResultsCompared with the blank group, the model group showed decreased total sperm count and motility (P<0.05, P<0.01), obvious damage in the testicular tissue and blood-testis barrier structure, reduced score of spermatogenic function (P<0.01), declined levels of GSH-Px and SOD in the testicular tissue (P<0.05), elevated level of MDA, and down-regulated protein levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin (P<0.05, P<0.01) and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, and β-catenin in the testicular tissue (P<0.05, P<0.01). After treatment, the testicular tissue, blood-testis barrier structure, and score of spermatogenic function (P<0.01) were improved in the Cuscutae Semen-Lycii Fructus granules group, Cuscutae Semen-Lycii Fructus total flavonoids group, and L-carnitine group. Compared with the model group, the treatment groups presented lowered levels of GSH-Px and SOD (P<0.05, P<0.01), and the Cuscutae Semen-Lycii Fructus granule group showed a decline in MDA level. The protein and mRNA levels of SIRT1, Nrf2, ZO-1, CX43, β-catenin, and occludin were up-regulated in the Cuscutae Semen-Lycii Fructus granules group and total flavonoids group (P<0.05, P<0.01). ConclusionThe herb pair Cuscutae Semen-Lycii Fructus can regulate the SIRT1/Nrf2 pathway to inhibit oxidative stress and alleviate the blood-testis barrier damage, thereby improving the spermatogenic function in the rat model of OAS. Total flavonoids may be the material basis for the therapeutic effect of Cuscutae Semen-Lycii Fructus.
5.Efficacy and safety comparison of roxadustat versus recombinant human erythropoietin combined with intravenous iron for renal anemia in patients undergoing maintenance hemodialysis
Jiang LIU ; Wenfei DING ; Li WEN
China Pharmacy 2025;36(19):2422-2427
OBJECTIVE To compare the efficacy and safety of roxadustat versus recombinant human erythropoietin (rHuEPO), each combined with intravenous iron supplementation, in the treatment of renal anemia (RA) in patients undergoing maintenance hemodialysis (MHD). METHODS A retrospective analysis was conducted on the medical records of 152 patients diagnosed with RA and receiving MHD at the Affiliated Hospital of Southwest Medical University between January 2022 and June 2024. According to the treatment regimen, patients were divided into observation group (n=72) and control group (n=80). Both groups of patients received MHD and intravenous iron therapy, with the observation group additionally receiving roxadustat and the control group receiving rHuEPO, both for a treatment duration of 12 weeks. Changes in anemia indicators, iron metabolism parameters, inflammatory markers, cardiac function parameters, quality of life scores before and after therapy, and adverse events during treatment were compared between the two groups. RESULTS After 12 weeks of treatment, both groups showed significant increase in hemoglobin, red blood cell count, hematocrit, serum iron, transferrin, total iron binding capacity, transferrin saturation, left ventricular ejection fraction, E/A ratio, cardiac output, 36-Item Short Form Health Survey score, and Kidney Disease Quality of Life Short Form score compared to baseline (P<0.05). Conversely, the levels of ferritin, C-reactive protein, interleukin-6, tumor necrosis factor-α, brain natriuretic peptide, and N-terminal pro-B-type natriuretic peptide were significantly reduced (P<0.05). The improvements in the observation group were significantly greater than those in the control group (P< 0.05). Moreover, the incidence of adverse events was significantly lower in the observation group compared to the control group (P<0.05). CONCLUSIONS Compared to rHuEPO combined with intravenous iron supplementation, roxadustat combined with intravenous iron supplementation is more effective in improving anemia, iron metabolism, inflammatory status, cardiac function, and quality of life in patients with RA undergoing MHD. Additionally, it demonstrates a better safety profile.
6.Analysis of the effect of dosimeter wearing position on effective dose estimation among interventional radiology workers
Xuanrong ZHANG ; Wen GUO ; Xian XUE ; Pin GAO ; Kaiyi WANG ; Xuan ZHANG ; Yanqiu DING ; Xiao LUO ; Wenfang MENG ; Jun CHAO
Chinese Journal of Radiological Health 2025;34(5):687-694
Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.
7.The interval of rescue treatment does not affect the efficacy and safety of Helicobacter pylori eradication: A prospective multicenter observational study.
Minjuan LIN ; Junnan HU ; Jing LIU ; Juan WANG ; Zhongxue HAN ; Xiaohong WANG ; Zhenzhen ZHAI ; Yanan YU ; Wenjie YUAN ; Wen ZHANG ; Zhi WANG ; Qingzhou KONG ; Boshen LIN ; Yuming DING ; Meng WAN ; Wenlin ZHANG ; Miao DUAN ; Shuyan ZENG ; Yueyue LI ; Xiuli ZUO ; Yanqing LI
Chinese Medical Journal 2025;138(12):1439-1446
BACKGROUND:
The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections.
METHODS:
This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups.
RESULTS:
A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups.
CONCLUSION:
The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs.
REGISTRATION
ClinicalTrials.gov , NCT05173493.
Humans
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Helicobacter Infections/drug therapy*
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Helicobacter pylori/pathogenicity*
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Male
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Female
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Prospective Studies
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Middle Aged
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Anti-Bacterial Agents/adverse effects*
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Adult
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Aged
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Treatment Outcome
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Proton Pump Inhibitors/therapeutic use*
8.Detection and sequence analysis of broad bean wilt virus 2 on Rehmannia glutinosa.
Xiao-Long DENG ; Jie YAO ; Lang QIN ; Shi-Wen DING ; Tie-Lin WANG ; Kun ZHANG ; Lei CHENG ; Zhen HE
China Journal of Chinese Materia Medica 2025;50(7):1741-1747
To clarify the occurrence and distribution of broad bean wilt virus 2(BBWV2) on Rehmannia glutinosa, this study collected 87 R. glutinosa samples with typical symptoms of viral disease such as chlorosis and crumple from Wenxian county and Wuzhi county in Jiaozuo city, Henan province and Qiaocheng district in Bozhou city, Anhui province. The BBWV2 CP target band was amplified from 37 R. glutinosa samples by RT-PCR technology. The total detection rate reached 42.5%, among which 43.0% was detected in samples from Henan province. The detection rate in samples from Anhui province was 37.5%. 37 BBWV2 CP sequences were obtained by cloning and sequencing of BBWV2 positive samples(data has been submitted to GenBank, accession numbers: PP407959-PP407995), and the sequence analysis of these CP sequences with 91 other BBWV2 isolates in GenBank showed a high genetic diversity with a consistency rate of 70.8%-100%. Meanwhile, phylogenetic analysis showed that BBWV2 could be divided into three groups according to CP sequences, among which the BBWV2 in R. glutinosa isolates obtained in this study were all located in group 3. This study identified the differences in the occurrence, distribution, and genetic diversity of BBWV2 in R. glutinosa from Henan province and Anhui province and provided a theoretical basis for the prevention and control of BBWV2.
Rehmannia/virology*
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Phylogeny
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Plant Diseases/virology*
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China
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Molecular Sequence Data
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Fabavirus/classification*
9.Effects of understory environmental factors on understory planting of medicinal plants.
Ding-Mei WEN ; Hong-Biao ZHANG ; Feng-Yuan QIN ; Chao-Qun XU ; Dou-Dou LI ; Bao-Lin GUO
China Journal of Chinese Materia Medica 2025;50(5):1164-1171
Understory planting of medicinal plants is a new planting mode that connects Chinese herbal medicine(CHM) with forest resources.The complex and variable understory environmental factors will inevitably affect the yield and quality of understory CHM.This research summarized the research progress on understory planting of medicinal plants based on forest types and environmental factors within the forest from the perspectives of understory light, air temperature and humidity, soil characteristics, and the interaction between crops within the forest.The results showed that the complex and variable light, temperature and humidity, and soil factors(such as fertility, acidity and alkalinity, and microorganisms) under the forest could affect the yield and quality of medicinal plants to varying degrees through physiological activities such as photosynthesis and respiration, resulting in a significant increase or decrease in yield and quality compared to open field cultivation.In addition, the competition or mutual benefit between different crops within the forest could lead to differences in the yield and quality of understory medicinal plants compared to open field cultivation.A reasonable combination of planting could achieve resource sharing and complementary advantages.Therefore, conducting systematic research on the effects of understory environmental factors on the yield and content of medicinal plants with different growth and development characteristics can provide theoretical guidance and technical references for formulating comprehensive strategies for understory planting of medicinal plants, such as selecting suitable medicinal plant varieties, optimizing planting density, and conducting reasonable forest management, thus contributing to the sustainable development and ecological protection of CHM.
Plants, Medicinal/growth & development*
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Forests
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Soil/chemistry*
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Environment
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Ecosystem
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Temperature
10.Theoretical discussion and research progress on treatment of glucocorticoid- induced osteoporosis with traditional Chinese medicine.
Ting-Ting XU ; Ying DING ; Xia ZHANG ; Long WANG ; Shan-Shan XU ; Chun-Dong SONG ; Wen-Sheng ZHAI ; Xian-Qing REN
China Journal of Chinese Materia Medica 2025;50(16):4437-4450
Glucocorticoid-induced osteoporosis(GIOP) is a serious metabolic bone disease caused by long-term application of glucocorticoids(GCs). Traditional Chinese medicine(TCM) has unique advantages in improving bone microstructure and antagonizing hormone toxicity. This paper systematically reviews the theoretical research, clinical application, and basic research progress of TCM intervention in GIOP. In terms of theoretical research, the theory of "kidney governing bone and generating marrow" indicates that the kidney is closely related to bone development, revealing that core pathogenesis of GIOP is Yin-Yang disharmony, which can be discussed using the theories of "Yin fire", "ministerial fire", and "Yang pathogen damaging Yin". Thus, regulating Yin and Yang is the basic principle to treat GIOP. In terms of clinical application, effective empirical prescriptions(such as Bushen Zhuanggu Decoction, Bushen Jiangu Decoction, and Zibu Ganshen Formula) and Chinese patent medicines(Gushukang Capsules, Hugu Capsules, Xianling Gubao Capsules, etc.) can effectively increase bone mineral density(BMD) and improve calcium and phosphorus metabolism. The combination of traditional Chinese and western medicine can reduce the risk of fracture and play an anti-GIOP role. In terms of basic research, it has been clarified that active ingredients of TCM(such as fraxetin, ginsenoside Rg_1, and salidroside) reduce bone loss and promote bone formation by inhibiting oxidative stress, ferroptosis, and other pathways, effectively improving bone homeostasis. Additionally, classical prescriptions(Modified Yiguan Decoction, Modified Qing'e Pills, Zuogui Pills, etc.) and Chinese patent medicines(Gushukang Granules, Lurong Jiangu Dropping Pills, Gubao Capsules, etc.) can improve bone marrow microcirculation, promote osteoblast differentiation, and inhibit bone cell apoptosis through multiple pathways, multiple targets, and multiple mechanisms. Through the above three aspects, the TCM research status on GIOP is elucidated in the expectation of providing reference for its diagnosis and treatment using traditional Chinese and western medicine treatment programs.
Osteoporosis/physiopathology*
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Humans
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Glucocorticoids/adverse effects*
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Drugs, Chinese Herbal/administration & dosage*
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Animals
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Medicine, Chinese Traditional
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Bone Density/drug effects*

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