1.Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach.
Yujia WANG ; Yan DI ; Yongqi LI ; Jing LU ; Bofan JI ; Yuxia ZHANG ; Zhiqing CHEN ; Sijie CHEN ; Bicheng LIU ; Rining TANG
Chinese Medical Journal 2025;138(1):68-78
BACKGROUND:
Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq).
METHODS:
Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS:
By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR.
CONCLUSIONS
Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals
;
Mice
;
Chronic Kidney Disease-Mineral and Bone Disorder/genetics*
;
Male
;
Disease Models, Animal
;
Mice, Inbred C57BL
;
Sphingolipids/metabolism*
;
Transcriptome/genetics*
;
Signal Transduction/genetics*
;
X-Ray Microtomography
;
Adenine
2.The epidemiology and distribution of hand fractures in Singapore.
Jin Xi LIM ; Lan Anh Thi LE ; Jared Ze Yang YEH ; Jia Jun Justin BOEY ; Vaikunthan RAJARATNAM
Singapore medical journal 2025;66(9):476-480
INTRODUCTION:
The aim of this study was to elucidate the epidemiology and distribution of hand fractures in Singapore.
METHODS:
A total of 701 hand fractures in 596 patients aged 21 years and above from a single centre were reviewed from 2010 to 2011. Details regarding the patient demographics, occupation, mechanism of injury, associated injuries and treatment were obtained.
RESULTS:
Hand fractures were particularly significant in patients between the ages of 21 and 40 years 58.9% of the total cases. The relative risk of hand fractures in males was 5.5 times greater than that in females. The majority of hand fractures occurred at the workplace (47.7%), with crush injury being the main mechanism of injury (33.6%). The most common locations of hand fracture were the little finger ray (31.2%) and distal phalanges (37.7%). There were 170 cases that underwent surgical fixation, which accounted for 24.3% of all fractures. Fixation rate was similar for both closed and open fractures but was significantly higher in the proximal and middle phalanges compared to the distal phalanx and metacarpal ( P < 0.001). With regards to surgical fixation methods, wires were commonly used in either tuft fractures (100.0%) or intra-articular fractures (69.9%), whereas plates and screws were commonly used in shaft fractures (65.5%).
CONCLUSION
The most significant population that sustained hand fractures in Singapore are young to middle-aged males who are skilled manual workers. The most commonly involved ray and location of hand fractures are the little finger ray and the distal phalanges, respectively, as they are in a relatively more exposed location.
Humans
;
Singapore/epidemiology*
;
Male
;
Female
;
Adult
;
Middle Aged
;
Fractures, Bone/surgery*
;
Hand Injuries/surgery*
;
Young Adult
;
Aged
;
Hand Bones/injuries*
;
Retrospective Studies
;
Fracture Fixation, Internal
3.Deploying artificial intelligence in the detection of adult appendicular and pelvic fractures in the Singapore emergency department after hours: efficacy, cost savings and non-monetary benefits.
John Jian Xian QUEK ; Oliver James NICKALLS ; Bak Siew Steven WONG ; Min On TAN
Singapore medical journal 2025;66(4):202-207
INTRODUCTION:
Radiology plays an integral role in fracture detection in the emergency department (ED). After hours, when there are fewer reporting radiologists, most radiographs are interpreted by ED physicians. A minority of these interpretations may miss diagnoses, which later require the callback of patients for further management. Artificial intelligence (AI) has been viewed as a potential solution to augment the shortage of radiologists after hours. We explored the efficacy of an AI solution in the detection of appendicular and pelvic fractures for adult radiographs performed after hours at a general hospital ED in Singapore, and estimated the potential monetary and non-monetary benefits.
METHODS:
One hundred and fifty anonymised abnormal radiographs were retrospectively collected and fed through an AI fracture detection solution. The radiographs were re-read by two radiologist reviewers and their consensus was established as the reference standard. Cases were stratified based on the concordance between the AI solution and the reviewers' findings. Discordant cases were further analysed based on the nature of the discrepancy into overcall and undercall subgroups. Statistical analysis was performed to evaluate the accuracy, sensitivity and inter-rater reliability of the AI solution.
RESULTS:
Ninety-two examinations were included in the final study radiograph set. The AI solution had a sensitivity of 98.9%, an accuracy of 85.9% and an almost perfect agreement with the reference standard.
CONCLUSION
An AI fracture detection solution has similar sensitivity to human radiologists in the detection of fractures on ED appendicular and pelvic radiographs. Its implementation offers significant potential measurable cost, manpower and time savings.
Humans
;
Singapore
;
Emergency Service, Hospital
;
Fractures, Bone/diagnostic imaging*
;
Artificial Intelligence
;
Retrospective Studies
;
Adult
;
Male
;
Female
;
Cost Savings
;
Middle Aged
;
Pelvic Bones/diagnostic imaging*
;
Reproducibility of Results
;
Aged
;
Sensitivity and Specificity
;
Radiography
4.Association between bone mineral density and vascular health in rheumatoid arthritis.
Chuanhui XU ; Yi Wye LAI ; Shih-Huan CHOU ; Xiaoe ZHANG ; Ee Tzun KOH ; Rinkoo DALAN ; Khai Pang LEONG
Singapore medical journal 2025;66(3):147-153
INTRODUCTION:
Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD).
METHODS:
We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2.
RESULTS:
We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV.
CONCLUSION
Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
Humans
;
Arthritis, Rheumatoid/complications*
;
Female
;
Male
;
Bone Density
;
Middle Aged
;
Cross-Sectional Studies
;
Vascular Stiffness
;
Aged
;
Singapore
;
Pulse Wave Analysis
;
Osteoporosis/complications*
;
Endothelium, Vascular/physiopathology*
;
Cardiovascular Diseases/complications*
;
Carotid-Femoral Pulse Wave Velocity
;
Hyperemia
5.Expert consensus on whole-course management of prostate cancer (2025 edition).
Chinese Journal of Oncology 2025;47(7):617-634
Prostate cancer represents a prevalent malignancy within the male genitourinary system. In recent years, its incidence in China has gradually increased, becoming a significant public health issue. While early detection correlates strongly with improved prognosis, the majority of newly diagnosed prostate cancer patients in China are already in intermediate or advanced stages, precluding curative-intent interventions and contributing to marked survival disparities. The progression of prostate cancer is lengthy, typically encompassing diagnosis, treatment, progression, metastasis, and death, accompanied by a decline in quality of life. Personalized treatment plans should be developed based on the disease stage and patient preferences. In non-metastatic prostate cancer, where the tumor is confined to the prostate, surgery and radiotherapy are the primary treatments, supplemented by neoadjuvant and adjuvant therapies to delay metastasis. For metastatic prostate cancer, systemic therapy is prioritized to prolong survival. In metastatic hormone-sensitive prostate cancer, controlling androgen levels is crucial, while treatment options for metastatic castration resistant prostate cancer are relatively limited, necessitating individualized and precise treatment. During prostate cancer management, prostate-specific antigen levels are closely linked to prognosis and require monitoring. Bone metastasis, the most common site in prostate cancer patients, often triggers skeletal-related events, demanding effective prevention and management. Treatment-related adverse reactions are also a clinical challenge, requiring balanced risk-benefit assessments and judicious drug selection to preserve quality of life. Rapid advancements in screening technologies, surgical innovations, drug development, and China-specific epidemiological factors further complicate decision-making in holistic prostate cancer management. To optimize the standardization of prostate cancer diagnosis and treatment in China, the Genitourinary Oncology Committee of Chinese Anti-cancer Association synthesized global guidelines, clinical evidence and clinical expertise, and addressed critical challenges in the whole-course management of prostate cancer to formulate a multidisciplinary consensus. The expert consensus on whole-course management of prostate cancer (2025 edition) establishes standardized protocols to guide clinical practice, improve treatment outcomes, and enhance patient quality of life.
Humans
;
Male
;
Prostatic Neoplasms/diagnosis*
;
Consensus
;
Prostate-Specific Antigen/blood*
;
Quality of Life
;
Prostatic Neoplasms, Castration-Resistant/pathology*
;
China
;
Bone Neoplasms/secondary*
;
Androgen Antagonists/therapeutic use*
6.LIU Zhibin's experience in treatment of subjective tinnitus with acupuncture based on the "kidney-bone-brain" axis.
Yunru WU ; Zhibin LIU ; Weixing FENG ; Weigang WANG ; Enzhao FAN ; Yanbin YAN
Chinese Acupuncture & Moxibustion 2025;45(6):808-812
This paper introduces Professor LIU Zhibin 's clinical experience in the treatment of subjective tinnitus with acupuncture based on the "kidney-bone-brain" axis. Professor LIU proposes that the disease is most closely related to the kidney and brain. The lesion is located in the brain, and the pathogenesis is kidney essence deficiency, marrow sea loss, and ear orifice dystrophy. The "kidney-bone-brain" shows close correlation in physiological function, pathological changes and treatment. According to the "kidney-bone-brain" axis, Professor LIU proposes that the treatment of subjective tinnitus should be tonifying kidney qi, tonifying essence and filling marrow, and the principle of local acupoint selection, touching bone acupuncture, matching distal acupoints and proximal acupoints, tonifying kidney and benefiting brain should be adopted. The acupoints of Tinggong (SI19) and Yifeng (TE17) are selected to be treated with touching bone acupuncture, combined with Taixi (KI3), Shenshu (BL23), Baihui (GV20) and Shenting (GV24), so as to achieve common benefit of kidney, bone and brain, and multi-angle treatment.
Humans
;
Acupuncture Therapy/history*
;
Tinnitus/physiopathology*
;
Acupuncture Points
;
Kidney/physiopathology*
;
Brain/physiopathology*
;
Bone and Bones/physiopathology*
;
Female
;
Male
;
Adult
;
Middle Aged
7.The pleiotropic role of MEF2C in bone tissue development and metabolism.
Hao-Jie XIAO ; Rui-Qi HUANG ; Sheng-Jie LIN ; Jin-Yang LI ; Xue-Jie YI ; Hai-Ning GAO
Acta Physiologica Sinica 2025;77(2):374-384
The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans
;
MEF2 Transcription Factors/physiology*
;
Bone and Bones/metabolism*
;
Animals
;
Bone Development/physiology*
;
Osteogenesis/physiology*
;
Myogenic Regulatory Factors/physiology*
8.Roles and mechanisms of TRIM family proteins in the regulation of bone metabolism.
Jing YANG ; Rui-Qi HUANG ; Ke XU ; Mian-Mian YANG ; Xue-Jie YI ; Bo CHANG ; Ting-Ting YAO
Acta Physiologica Sinica 2025;77(3):472-482
Tripartite motif-containing (TRIM) family proteins are crucial E3 ubiquitin ligases that have garnered significant attention for their regulatory roles in bone metabolism in recent years. This article reviews the function and regulatory mechanisms of TRIM family proteins in bone metabolism, focusing on their dual roles in bone formation and resorption. It also provides a detailed analysis of signaling pathways and molecular mechanisms by which TRIM family members regulate the activities of osteoblasts and osteoclasts. Research findings suggest that modulating the expression or activity of TRIM family proteins could be beneficial for treating bone diseases such as osteoporosis. This review highlights the molecular mechanisms of TRIM family members in bone physiology and pathology, aiming to provide theoretical basis and scientific guidance for developing novel therapeutic strategies for bone diseases.
Humans
;
Ubiquitin-Protein Ligases/physiology*
;
Bone and Bones/metabolism*
;
Animals
;
Tripartite Motif Proteins/physiology*
;
Osteoclasts/metabolism*
;
Osteoblasts/metabolism*
;
Signal Transduction/physiology*
;
Osteogenesis/physiology*
9.Era value and new directions of traditional Chinese medicine in preventing and treating osteoporosis from perspective of "bone health program".
Yi-Li ZHANG ; Chuan-Rui SUN ; Kai SUN ; Ai-Li XU ; Hao SHEN ; He YIN ; Ling-Hui LI ; Li-Guo ZHU ; Xu WEI
China Journal of Chinese Materia Medica 2025;50(3):569-574
Facing the requirements of promoting the healthy China initiative and improving people's health, the "bone health program" was proposed in 2024. In-depth development of a traditional Chinese medicine(TCM) prevention and control system is of strategic significance to the implementation of the "bone health program". Focusing on osteoporosis(OP), a representative disease affecting people's bone health, this paper concludes that accelerating the research on the prevention and control of OP by TCM is conducive to enhancing the knowledge and awareness of OP among the public, and it is beneficial to revealing the evolutionary pattern of OP and improving the understanding and management of this disease. Additionally, it can provide an overall framework for and strengthen the systematicity and completeness of the research on the prevention and treatment of OP by TCM. Meanwhile, it can help to explore new research paradigms and optimize the existing research model, so as to promote innovative breakthroughs in the prevention and treatment of bone health-related diseases by TCM. Under the overall layout of the "bone health program", importance should be attached to the early prevention and the innovation of very early diagnosis and intervention of OP. Emphasis should be put on the discovery of the target network of disease and treatment mechanism for revealing the core pathogenesis of OP and the therapeutic mechanism of TCM. In addition to local lesions of the bone and its clinical outcomes, attention should be paid to the development of multiple metabolic complications. The fusion of advanced interdisciplinary technologies should be promoted for OP and its complications, and thus a research and development system based on clinical application scenarios and driven by big data can be built. The measures above will facilitate the progress in the prevention and treatment of OP and other bone diseases by TCM and provide new momentum for enriching and deepening the research connotation of the "bone health program".
Osteoporosis/therapy*
;
Humans
;
Medicine, Chinese Traditional/methods*
;
Drugs, Chinese Herbal/therapeutic use*
;
China
;
Bone and Bones/drug effects*
10.Influence of iron metabolism on osteoporosis and modulating effect of traditional Chinese medicine.
Yi-Li ZHANG ; Bao-Yu QI ; Chuan-Rui SUN ; Xiang-Yun GUO ; Shuang-Jie YANG ; Ping LIU ; Xu WEI
China Journal of Chinese Materia Medica 2025;50(3):575-582
Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy*
;
Humans
;
Iron/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
;
Animals
;
Medicine, Chinese Traditional
;
Bone and Bones/drug effects*

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