OBJECTIVE: To analyze the acupoint selection patterns and core prescriptions of acupuncture for polycystic ovary syndrome (PCOS) using data mining, and to explore the molecular mechanisms of core acupoints through network acupuncture medicine. METHODS: The randomized controlled trials (RCTs) on acupuncture for PCOS published from January 1, 2004 to July 21, 2024 were retrieved from CNKI, VIP, Wanfang, PubMed, and Web of Science databases. R software (version 4.4.0) was used for acupoint frequency and association rule analysis to identify core acupoint prescriptions. Potential targets were predicted via the STITCH and Swiss Target Prediction databases, and a "core prescription-active compounds-targets- PCOS" network was constructed. Cytoscape 3.7.1 was applied to build protein-protein interaction (PPI) networks of potential targets of core acupoint prescriptions. Key therapeutic targets were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses using the DAVID and Microbioinformatics platforms. RESULTS: A total of 176 RCTs were included, covering 208 prescriptions and 89 acupoints. The five most frequently used acupoints were Guanyuan (CV4), Sanyinjiao (SP6), Zigong (EX-CA1), Zusanli (ST36) and Zhongji (CV3). Association rule analysis yielded 13 core acupoint combinations, with Guanyuan (CV4), Sanyinjiao (SP6), Zigong (EX-CA1) and Zusanli (ST36) as the core prescription. Twenty-seven active compounds were involved, with 852 potential therapeutic targets, among which 208 targets overlapped with PCOS-related targets. Network acupuncture medicine analysis suggested that the core prescription may act through targets such as estrogen receptor 1 (ESR1), proto-oncogene tyrosine-protein kinase Src (SRC), signal transducer and activator of transcription 3 (STAT3), peroxisome proliferator-activated receptor gamma (PPARG), and RAC-alpha serine/threonine-protein kinase (AKT1). GO and KEGG analyses indicated that the main pathways included the hypoxia-inducible factor 1 (HIF-1) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, involving processes such as signal transduction, receptor complex formation, and cytokine activity. CONCLUSION The core acupoint prescription for PCOS might exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for mechanistic research on acupoint prescriptions.
Humans ; Acupuncture Therapy ; Data Mining ; Acupuncture Points ; Polycystic Ovary Syndrome/metabolism* ; Female ; Protein Interaction Maps ; Randomized Controlled Trials as Topic

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

OBJECTIVE: To compare the biomechanical properties of personalized Y-shaped plates with horizontal plates, vertical plates, and traditional Y-shaped plates in the treatment of distal humeral intra-articular fractures through finite element analysis, and to evaluate their potential for clinical application. METHODS: The study selected a 38-year-old male volunteer and obtained a three-dimensional model of the humerus by scanning his upper limbs using a 64-slice spiral CT. Four types of fracture-internal fixation models were constructed using Mimics 19.0, Geomagic Wrap 2017, Creo 6.0, and other software: horizontal plates, vertical plates, traditional Y-shaped plate, and personalized Y-shaped plate. The models were then meshed using Hypermesh 14.0 software, and material properties and boundary conditions were defined in Abaqus 6.14 software. AnyBody 7.3 software was used to simulate elbow flexion and extension movements, calculate muscle strength, joint forces, and load torques, and compare the peak stress and maximum displacement of the four fixation methods at different motion angles (10°, 30°, 50°, 70°, 90°, 110°, 130°, 150°) during elbow flexion and extension. RESULTS: Under dynamic loading during elbow flexion and extension, the personalized Y-shaped plate exhibits significant biomechanical advantages. During elbow flexion, the peak internal fixation stress of the personalized Y-shaped plate was (28.8±0.9) MPa, which was significantly lower than that of the horizontal plates, vertical plates, and traditional Y-shaped plate ( <i>Pi><0.05). During elbow extension, the peak internal fixation stress of the personalized Y-shaped plate was (18.1±1.6) MPa, which was lower than those of the other three models, with significant differences when compared with horizontal plates and vertical plates ( <i>Pi><0.05). Regarding the peak humeral stress, the personalized Y-shaped plate model showed mean values of (10.9±0.8) and (13.1±1.4) MPa during elbow flexion and extension, respectively, which were significantly lower than those of the other three models ( <i>Pi><0.05). Displacement analysis showed that the maximum displacement of the humerus with the personalized Y-shaped plate during elbow flexion was (2.03±0.08) mm, slightly higher than that of the horizontal plates, but significantly lower than that of the vertical plates, showing significant differences ( <i>Pi><0.05). During elbow extension, the maximum displacement of the humerus with the personalized Y-shaped plate was (1.93±0.13) mm, which was lower than that of the other three models, with significant differences when compared with vertical plates and traditional Y-shaped plates ( <i>Pi><0.05). Stress contour analysis showed that the stress of the personalized Y-shaped plate was primarily concentrated at the bifurcation of the Y-shaped structure. Displacement contour analysis showed that the personalized Y-shaped plate effectively controlled the displacement of the distal humerus during both flexion and extension, demonstrating excellent stability. CONCLUSION The personalized Y-shaped plate demonstrates excellent biomechanical performance in the treatment of distal humeral intra-articular fractures, with lower stress and displacement, providing more stable fixation effects.
Humans ; Male ; Adult ; Healthy Volunteers ; Finite Element Analysis ; Tomography, Spiral Computed ; Models, Anatomic ; Biomechanical Phenomena ; Humeral Fractures, Distal/surgery* ; Fracture Fixation, Internal/instrumentation* ; Bone Plates ; Computer Simulation ; Precision Medicine/methods* ; Elbow Joint/surgery* ; Elbow/surgery* ; Humerus/surgery* ; Torque ; Stress, Mechanical ; Intra-Articular Fractures/surgery* ; Prosthesis Design/methods* ; Imaging, Three-Dimensional ; Range of Motion, Articular

OBJECTIVE: To explore the application progress and clinical value of digital technologies in the surgical treatment of ankylosing spondylitis (AS). METHODS: By systematically reviewing domestic and international literature, the study summarized the specific application scenarios, operational procedures, and technical advantages of digital technologies [including preoperative three-dimensional (3D) planning, intraoperative real-time navigation, robot-assisted surgery, and 3D printing] in AS surgery, and analyzed their impact on surgical accuracy, complication rates, and clinical outcomes. RESULTS: Digital technologies significantly improve the precision and safety of AS surgery. Preoperative 3D planning enables personalized surgical protocols; intraoperative navigation systems dynamically adjusts surgical trajectories, reducing the risk of iatrogenic injury; robot-assisted surgery can minimize human errors and enhance implant positioning accuracy; 3D-printed anatomical models and guides optimize the correction of complex spinal deformities. Furthermore, the combined applications of these technologies shorten operative time, reduce intraoperative blood loss, decrease postoperative complications (e.g., infection, nerve injury), and accelerate functional recovery. CONCLUSION Through multidimensional integration and innovation, digital technologies provide a precise and minimally invasive solution for AS surgical treatment. Future research should focus on their synergy with biomaterials and intelligent algorithms to further refine surgical strategies and improve long-term prognosis.
Humans ; Spondylitis, Ankylosing/diagnostic imaging* ; Printing, Three-Dimensional ; Surgery, Computer-Assisted/methods* ; Robotic Surgical Procedures/methods* ; Imaging, Three-Dimensional ; Postoperative Complications/prevention & control* ; Digital Technology ; Models, Anatomic

OBJECTIVE: To establish digital model of Ideberg typeⅡregional glenoid fracture anatomical plate with 3D metal printing technology. METHODS: The scapular imaging data of a 34-year-old healthy male volunteer were retrospectively selected. Mimics 15.01, NX 12.0 and other software were used to design Ideberg typeⅡ regional scapular fracture guide plate system. STL data were input into a metal 3D printer to print 1∶1 scapular model and anatomical plate of scapular pelvis with guide sleeve. The fit of the plate was tested in vitro and the accuracy of the screw position was evaluated by imaging. The printing time of scapular model, design of the nail path and making time of the anatomic guided plate were recorded. RESULTS: 3D metal-printed Ideberg typeⅡ guide plate for scapular fracture fitted well to 3D printed scapular model, the locking screw was oriented accurately, and X-ray and CT showed good screw position. The printing time of scapula model, time of nail path design and special-shaped anatomical guide plate production were 52.0, 15.0 and 320 min, respectively. CONCLUSION Anatomical plates based on 3D metal printing technology could achieve good adhesion of Ideberg typeⅡ regional fractures and precise screw placement, providing a new and accurate surgical method for the treatment of Ideberg typeⅡ glenoid fractures.
Humans ; Printing, Three-Dimensional ; Male ; Adult ; Bone Plates ; Fractures, Bone/diagnostic imaging* ; Fracture Fixation, Internal/methods* ; Pelvic Bones/surgery* ; Metals ; Scapula/surgery* ; Models, Anatomic

Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by Transwell^TM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
Humans ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Antibodies, Monoclonal/pharmacology* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Cell Line, Tumor ; Antigens, CD/immunology* ; Lymphocyte Activation Gene 3 Protein ; A549 Cells ; I-kappa B Kinase/metabolism* ; Jurkat Cells ; Matrix Metalloproteinase 9/metabolism*

PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1 - L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (F_z) of THOR-AV and THUMS changed in the similar trend. The maximum F_z ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (M_y) and the time when the maximum M_y occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of M_y measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION The F_z of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on F_z. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map M_y directly because they are very different in ATD and HBM. The M_y of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
Humans ; Lumbar Vertebrae/injuries* ; Finite Element Analysis ; Biomechanical Phenomena ; Manikins ; Spinal Injuries/physiopathology*

BACKGROUND: Chronic constipation is a long-term problem that decreases children's quality of life. Information and communication technology devices have developed rapidly in recent decades and have had various impacts on children. This prospective cohort study examined the association between television/digital versatile disc (TV/DVD) screen exposure time at age 1 and the risk of chronic constipation at age 3. METHODS: Data from 63,697 infants in the Japan Environment and Children's Study (JECS) were analyzed. We divided participants into five groups according to TV/DVD exposure time per day: no exposure (0 h), short exposure (<1 h), middle exposure (1.0-<2.0 h), long exposure (2.0-<4.0 h), and very long exposure (≥4 h). Logistic regression analysis was performed to assess the association between TV/DVD exposure time and the risk of constipation. For logistic regression analysis, odds ratios (ORs) were adjusted for sex, parents' education, household income, nursery school, feeding contents, and obesity. The interaction between the sexes was also examined. RESULTS: The prevalence of constipation for males, females, and all participants at age 3 was 9.3, 11.0, and 10.1%, respectively. The TV/DVD screen time distribution per day at age 1 was 10.6% for none, 34.1% for short, 29.9% for middle, 19.2% for long, and 6.2% for the very long exposure group. After adjusting for confounding factors, a dose-response pattern was identified between TV/DVD exposure time and constipation in all participants (p for trend < 0.001). The adjusted ORs increased progressively in the short (OR 1.15, 95% confidence interval [CI] 1.04-1.27), middle (OR 1.22, 95% CI 1.11-1.35), long (OR 1.37, 95% CI 1.24-1.52), and very long exposure groups (OR 1.53, 95% CI 1.35-1.74). This association was not significantly different between the sexes (p for interaction = 0.36). CONCLUSIONS Longer TV/DVD exposure time at age 1 was associated with the risk of chronic constipation at age 3. Excessive screen exposure may need to be avoided from infancy to decrease the risk of chronic constipation in later years.
Humans ; Constipation/etiology* ; Male ; Female ; Japan/epidemiology* ; Television/statistics & numerical data* ; Child, Preschool ; Infant ; Screen Time ; Prospective Studies ; Risk Factors ; Chronic Disease/epidemiology* ; Prevalence

BACKGROUND: Long screen time hours may be associated with behavioral problems in children. To better understand the relationship between children's behavioral problems and screen time, it the associated risk factors must be subdivided based on the purpose underlying screen use. This study examined the relationship between screen time based on intended usage and behavioral problems in Japan. METHODS: This study included 3,332 children aged between 7-17 years from the Hokkaido Study on Environment and Children's Health. From October 2020 to October 2021, the children and their parents answered questionnaires on the children's screen use duration (never used, <30 min, ≥30 min & <1 hour, ≥1 h & <2 h, ≥2 h) based on seven intended usage categories: watching television/video, video gaming, reading books/comics, sending/receiving e-mail/messages, browsing/posting on social networking services, studying for classes/homework, drawing/editing pictures/photos/videos, along with the Strengths and Difficulties Questionnaire (SDQ). Logistic regression was used to analyze the association between screen time, purpose of children's screen use, and behavioral problems across the 13 SDQ total scores. RESULTS: The mean ± standard deviation age of the participants was 12.4 ± 2.4-years-old, 487 (14.6%) children were determined to have behavioral problems, and the duration of screen time increased with their age. The children's primary purposes for screen use were watching television/video, video gaming, sending/receiving e-mail/messages, and browsing/posting on social networking services. Children who reported playing video games for ≥2 hours on weekdays had higher odds of problematic total difficulties scores than never user (Odds Ratio: 2.10, 95% confidence interval: 1.45-3.06). CONCLUSION Long video gaming screen time is associated with behavioral issues, hyperactivity/inattention, and prosocial behaviors in children. Conversely, watching television and videos for 30 min-1 h per day, using e-mail or messaging, and using social networking services were significantly association with reduced odds ratio for peer relationship problems as compared to children who never engaged in these activities. Longitudinal follow-up is needed to further examine screen time and problem behaviors.
Humans ; Screen Time ; Child ; Japan/epidemiology* ; Male ; Female ; Adolescent ; Problem Behavior/psychology* ; Surveys and Questionnaires ; Child Behavior ; Television/statistics & numerical data* ; Video Games/statistics & numerical data*

Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides