1.Mechanism of Zuogui Pills in regulating bone metabolism through OXT/OXTR feed-forward loop based on theory of "all marrows dominated by brain".
Yan-Chen FENG ; Ya-Li LIU ; Xue DANG ; Lu SUN ; Jin-Yao LI ; Jia-Bin SONG ; Shun-Zhi YANG ; Fei-Xiang LIU
China Journal of Chinese Materia Medica 2025;50(10):2761-2768
Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals
;
Rats, Sprague-Dawley
;
Rats
;
Female
;
Drugs, Chinese Herbal/administration & dosage*
;
Oxytocin/genetics*
;
Receptors, Oxytocin/genetics*
;
Humans
;
Osteoporosis, Postmenopausal/genetics*
;
Bone and Bones/drug effects*
;
Brain/drug effects*
;
Bone Marrow/drug effects*
2.Methods for enhancing image quality of soft tissue regions in synthetic CT based on cone-beam CT.
Ziwei FU ; Yechen ZHU ; Zijian ZHANG ; Xin GAO
Journal of Biomedical Engineering 2025;42(1):113-122
Synthetic CT (sCT) generated from CBCT has proven effective in artifact reduction and CT number correction, facilitating precise radiation dose calculation. However, the quality of different regions in sCT images is severely imbalanced, with soft tissue region exhibiting notably inferior quality compared to others. To address this imbalance, we proposed a Multi-Task Attention Network (MuTA-Net) based on VGG-16, specifically focusing the enhancement of image quality in soft tissue region of sCT. First, we introduced a multi-task learning strategy that divides the sCT generation task into three sub-tasks: global image generation, soft tissue region generation and bone region segmentation. This approach ensured the quality of overall sCT image while enhancing the network's focus on feature extraction and generation for soft tissues region. The result of bone region segmentation task guided the fusion of sub-tasks results. Then, we designed an attention module to further optimize feature extraction capabilities of the network. Finally, by employing a results fusion module, the results of three sub-tasks were integrated, generating a high-quality sCT image. Experimental results on head and neck CBCT demonstrated that the sCT images generated by the proposed MuTA-Net exhibited a 12.52% reduction in mean absolute error in soft tissue region, compared to the best performance among the three comparative methods, including ResNet, U-Net, and U-Net++. It can be seen that MuTA-Net is suitable for high-quality sCT image generation and has potential application value in the field of CBCT guided adaptive radiation therapy.
Cone-Beam Computed Tomography/methods*
;
Humans
;
Image Processing, Computer-Assisted/methods*
;
Artifacts
;
Algorithms
;
Bone and Bones/diagnostic imaging*
;
Neural Networks, Computer
3.Research progress of bioactive scaffolds in repair and regeneration of osteoporotic bone defects.
Yuangang WU ; Kaibo SUN ; Yi ZENG ; Bin SHEN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):100-105
OBJECTIVE:
To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects.
METHODS:
Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods.
RESULTS:
The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells.
CONCLUSION
With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans
;
Tissue Scaffolds/chemistry*
;
Bone Regeneration
;
Osteoporosis/therapy*
;
Tissue Engineering/methods*
;
Biocompatible Materials/chemistry*
;
Printing, Three-Dimensional
;
Calcium Phosphates/chemistry*
;
Osteogenesis
;
Ceramics
;
Cell Differentiation
;
Hydrogels
;
Bioprinting
;
Bone and Bones
4.Applications and prospects of graphene and its derivatives in bone repair.
Zhipo DU ; Yizhan MA ; Cunyang WANG ; Ruihong ZHANG ; Xiaoming LI
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(1):106-117
OBJECTIVE:
To summarize the latest research progress of graphene and its derivatives (GDs) in bone repair.
METHODS:
The relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed.
RESULTS:
The application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior.
CONCLUSION
GDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.
Graphite/pharmacology*
;
Tissue Engineering/methods*
;
Humans
;
Osteogenesis/drug effects*
;
Biocompatible Materials/pharmacology*
;
Bone Regeneration
;
Tissue Scaffolds/chemistry*
;
Cell Differentiation
;
Bone and Bones
;
Bone Substitutes/chemistry*
;
Animals
5.Application of nickel-titanium shape memory staples in treatment of multiple metatarsal fractures.
Jie CHEN ; Zhen YIN ; Weibo ZHOU ; Wen TAN ; Fulin ZHOU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(2):146-150
OBJECTIVE:
To investigate the effectiveness of nickel-titanium shape memory staples in treating multiple metatarsal fractures.
METHODS:
The clinical data of 27 patients with multiple metatarsal fractures who were treated between January 2022 and June 2023 and met the selection criteria were retrospectively analysed. The cohort consisted of 16 males and 11 females, aged 33-65 years (mean, 47.44 years). The causes of injury included heavy object impact in 11 cases, traffic accidents in 9 cases, and crush in 7 cases. Simultaneous fractures of 2, 3, 4, and 5 bones occurred in 6, 6, 4, and 8 cases, respectively, with tarsometatarsal joint injury in 3 cases. Fixation was performed using staples for 16, 22, and 9 fractures in the metatarsal neck, shaft, and the base, respectively, and 5 tarsometatarsal joint injuries. Preoperative soft tissue injuries were identified in 8 cases and classified according to the Tscherne-Oestern closed soft tissue injury classification as type Ⅰ in 5 cases and type Ⅱ in 3 cases. One case of type Ⅱexhibited preoperative skin necrosis. The patients were treated with fixation using nickel-titanium shape memory staples. Complications and fracture healing were documented. At last follow-up, the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was used to evaluate the function, and the visual analogue scale (VAS) score was used to evaluate the pain.
RESULTS:
The 27 patients were followed up 9-19 months (mean, 12.4 months). Postoperative X-ray films revealed no loss of fracture reduction, and all fractures achieved bony union. No internal fixator loosening, breakage, or other mechanical failures was observed. The mean fracture healing time was 3.13 months (range, 3-4 months). Postoperatively, 4 cases (2 of Tscherne-Oestern type Ⅰ, 2 of type Ⅱ) developed superficial skin necrosis, which resolved with dressing changes. No infection was observed in the remaining patients, and all wounds healed. At last follow-up, the AOFAS forefoot score ranged from 70 to 95, with an average of 86.6, of which 19 cases were excellent, 6 cases were good, and 2 cases were fair, with an excellent and good rate of 92.6%; the VAS score ranged from 0 to 3, with an average of 0.9, of which 24 cases were excellent, and 3 cases were good, with an excellent and good rate of 100%.
CONCLUSION
The use of nickel-titanium shape memory staples in the treatment of multiple metatarsal fractures can effectively protect local skin and soft tissues and minimize secondary damage associated with internal fixator insertion. It is a viable surgical option for management of multiple metatarsal fractures.
Humans
;
Male
;
Female
;
Middle Aged
;
Adult
;
Titanium
;
Nickel
;
Retrospective Studies
;
Fracture Fixation, Internal/instrumentation*
;
Aged
;
Metatarsal Bones/surgery*
;
Fractures, Bone/surgery*
;
Treatment Outcome
;
Sutures
;
Fractures, Multiple/surgery*
6.Progress of research on the gut microbiome and its metabolite short-chain fatty acids in postmenopausal osteoporosis: a literature review.
Yao CHEN ; Ying XIE ; Xijie YU
Frontiers of Medicine 2025;19(3):474-492
Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease caused by the decrease in estrogen levels after menopause. It leads to bone loss, microstructural damage, and an increased risk of fractures. Studies have found that the gut microbiota and its metabolites can regulate bone metabolism through the gut-bone axis and the gut-brain axis. As research progresses, PMOP has been found to be associated with gut microbiota dysbiosis and Th17/Treg imbalance. The gut microbiota is closely related to the development and differentiation of Treg and Th17 cells. Among them, the metabolites of the gut microbiota such as short-chain fatty acids (SCFAs) can regulate the differentiation of effector T cells by acting on molecular receptors on immune cells, thereby regulating the bone immune process. The multifaceted relationship among the gut microbiota, SCFAs, Th17/Treg cell-mediated bone immunity, and bone metabolism is eliciting attention from researchers. Through a review of existing literature, we have comprehensively summarized the effects of the gut microbiota and SCFAs on PMOP, especially from the perspective of Th17/Treg balance. Regulating this balance may provide new opportunities for PMOP treatment.
Humans
;
Gastrointestinal Microbiome/immunology*
;
Fatty Acids, Volatile/metabolism*
;
Osteoporosis, Postmenopausal/immunology*
;
Female
;
T-Lymphocytes, Regulatory/metabolism*
;
Th17 Cells/metabolism*
;
Dysbiosis/immunology*
;
Bone and Bones/metabolism*
7.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
8.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
9.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
10.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*

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