AIM:This study aimed to identify the key active components and signaling pathways in the tradi-tional Chinese medicine Fructus Aurantii that contribute to the prevention and treatment of cardiac hypertrophy,along with experimental validation.METHODS:H9C2 cardiomyocytes were pretreated with nobiletin(NOB)for 1 h and then ex-posed to 100 nmol/L angiotensin Ⅱ(Ang Ⅱ)for 24 h.RT-qPCR was used to quantify the mRNA expression of hypertrophy-related genes,including atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and myosin heavy chain 7(MYH7).Immunofluorescence staining was employed to assess the surface area of cardiomyocytes.Additionally,a kit was utilized to measure levels of pyroptosis-related factors such as lactate dehydrogenase(LDH),interleukin-1β(IL-1β),IL-18 and caspase-1,while Western blot was performed to evaluate the expression of gasdermin D and caspase-1.RESULTS:Network pharmacology analyses indicated that NOB is the key active component in Fructus Aurantii that regu-lates cardiac hypertrophy,potentially through the pyroptosis pathway.Further molecular biology experiments confirmed that NOB inhibits Ang Ⅱ-induced cardiac hypertrophy and pyroptosis.Furthermore,the involvement of the pyroptosis pathway was highlighted in the protective effects of NOB against cardiac hypertrophy.CONCLUSION:The active compo-nent NOB in the traditional Chinese medicine Fructus Aurantii alleviates cardiac hypertrophy by inhibiting pyroptosis.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

Deep medullary veins(DMVs)are critical components of the cerebral medullary venous system,responsible for venous drainage of the deep cerebral white matter.Recent research indicates that DMVs are closely related to cerebral small vessel disease(CSVD)and associated cognitive disorders.The morphological structure of DMVs can be clearly visualized on susceptibility weighted imaging and quantitative susceptibility mapping,which could potentially serve as markers for assessing the severity of CSVD.This article reviewed the anatomical characteristics and physiological functions of DMVs,as well as the mechanistic correlations between DMVs and various CSVD imaging markers,aiming to provide novel theoretical insights for early diagnosis and clinical management of CSVD.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective:To observe the early clinical efficacy of 3D-printed modular supporting prosthesis for reconstruction of lacunar bone defect caused by giant cell tumor of the distal femur.Methods:From May 2018 to July 2023, a total of 9 patients with giant cell tumor of the distal femur were treated with 3D-printed modular supporting prosthesis to reconstruct lacunar bone defects in the Department of Orthopedics, West China Hospital, Sichuan University. There were 4 males and 5 females, aged 30.8±6.1 years (range, 24-44 years), 5 cases on the left side, 4 cases on the right side, 2 cases of Campanacci grade I, 7 cases of Campanacci grade II. The anteroposterior and lateral X-ray films and T-SMART tomosynthesis imaging of the knee joint were taken to observe the bone graft healing and osseointegration after operation. Musculoskeletal Tumor Society (MSTS)-93 was used to evaluate knee function, and visual analogue scale (VAS) was used to evaluate knee pain.Results:All patients were successfully operated and followed up for an average of 30.8±7.5 months (range, 18-42 months). The operation time was 124.2±23.6 min, and the intraoperative blood loss was 105.6±17.4 ml. All autografts showed bony union at the graft-host junction, and the healing time was 3.3±0.4 months (range, 3.0-4.0 months). At 6 months after surgery, T-SMART tomosynthesis imaging showed that the gap between the prosthesis-bone interface was less than 1 mm in all patients. At the last follow-up, the thickness of residual subchondral bone was 5.7±1.3 mm, which was greater than that before operation 2.2±0.8 mm, and the difference was statistically significant ( t=10.823, P<0.001). At the last follow-up, the score of MSTS-93 was 26.7±2.4, which was higher than that before operation 18.8±3.7, and the difference was statistically significant ( t=5.367, P<0.001). At the last follow-up, the range of motion of the knee joint was 122.8°±9.1°, which was higher than that before operation 108.3°±6.1°, and the difference was statistically significant ( t=3.970, P<0.001). All patients were able to walk normally, go up and down stairs and other daily activities, and 7 patients were able to complete squats. At the last follow-up, there was no local tumor recurrence, distant metastasis, death, joint infection, pain (VAS score was 0), delayed wound healing, joint degeneration, prosthesis loosening or articular surface collapse. Conclusion:Reconstruction of lacunar bone defect caused by giant cell tumor of distal femur with 3D-printed modular supporting prosthesis can effectively improve knee joint function and osseointegration, and the short-term clinical results are satisfactory.

Objective:To explore the early and mid-term efficacy of three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee.Methods:A retrospective analysis was conducted on the data of 24 patients who underwent reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee using 3D-printed customized porous prostheses at West China Hospital of Sichuan University from June 2015 to June 2021. There were 14 female cases and 10 male cases, with an average age of 28.9±16.5 years (range, 12-61 years), 12 cases at the distal end of the femur and 12 cases at the proximal end of the tibia. Tumor types: 16 cases of osteosarcoma, 4 cases of Ewing's sarcoma, 2 cases of chondrosarcoma, and 2 case of parosteal osteosarcoma. All patients were classified as Enneking stage IIB. Record the oncology results of the patients, the length of tumor segment resection, and the remaining bone length at the distal femur or proximal tibia, as well as complications, systemic metastasis and imaging changes. The bone integration at the prosthesis-bone interface was evaluated by tomosynthesis-shimadzu metal artifact reduction technology (T-SMART). Limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score and knee range of motion assessment.Results:All 24 patients successfully completed the surgery and were followed up, with an average follow-up time of 51.8±12.7 months (range, 32-99 months). The length of femoral osteotomy was 241.1±66.2 mm (range, 150.6-333.4 mm), and the length of tibial osteotomy was 198.6±35.6 mm (range, 156.6-287.6 mm). The remaining bone length at the epiphyseal end around the knee joint (from the knee joint plane to the osteotomy plane of the distal femur or proximal tibia) was 52.6±11.0 mm (range, 31.1-77.5 mm). At the last follow-up, 23 patients survived tumor-free, while one patient died due to lung metastasis 54 months after the operation. One patient had prosthesis fracture 75 months after the operation, two patients had aseptic loosening 6 and 8 months after the operation, and the T-SMART of the remaining 20 patients showed that the implanted prostheses all achieved good osseointegration. At the last follow-up, the range of motion of the knee joint was 126.2°±7.5° (range, 110.0°-140.0°), and the MSTS-93 score was 26.7±1.8 points (range, 23-30 points). Among them, the MSTS-93 score of the femoral prosthesis was 26.7±1.6 points (range, 24-29 points), and the MSTS-93 score of the tibial prosthesis was 26.9±1.9 points (range, 23-30 points). The average knee range of motion was 126.2°±7.5° (range, 110°-140°), and the MSTS-93 functional score was 26.7±1.8 points (range, 23-30 points) at the last follow-up. The femoral component had an average score of 26.7±1.6 points (range, 24-29 points), while the tibial component had an average score of 26.9±1.9 points (range, 23-30 points).Conclusion:The application three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee can preserve the joint, restore limb function well, and have a low incidence of prosthesis complications, with good clinical efficacy in the early and middle stages.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective:To determine whether spinal cord injury (SCI) triggers secondary neuroinflammation and neuronal injury in remote brain regions by impairing the drainage function of the meningeal lymphatic vessels (MLVs).Methods:Fifty-two female C57BL/6 mice were assigned with the random number table into four groups ( n=13 per group): sham group, SCI group, adeno-associated virus negative control group (negative control group), and adeno-associated virus overexpressing VEGF-C group (VEGF-C group). The sham group underwent laminectomy without spinal cord injury. In the SCI group, negative control group and VEGF-C group, T 9 contusion was made to establish the SCI models using a modified Allen′s impactor. At 4 weeks before SCI modeling, the negative control group and VEGF-C group were injected via the cisterna magna with 3 μl adeno-associated virus for negative control or adeno-associated virus for VEGF-C overexpression. At 56 days after injury, Alexa Fluor? 647 ovalbumin conjugate (OVA-647) was injected via the cisterna magna as a tracer. Two hours later, the proportion of OVA-647 in the deep cervical lymph nodes (dCLN) was detected. Immunofluorescence was performed to assess the proportion of MLVs marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and expression levels of microglial marker ionized calcium-binding adaptor molecule 1 (Iba1) in the cerebral cortex, hippocampus, midbrain, and thalamus across the experimental groups. ELISA was employed to quantify the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and Nissl staining was used to assess neuronal counts in these regions. Results:At 56 days after injury, the OVA-647 proportion in the dCLN was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas the SCI group and negative control group showed a lower OVA-647 proportion in the dCLN than the VEGF-C group ( P<0.05). At 56 days after injury, the dural LYVE-1 proportion was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas it was lower in the SCI group and negative control group than that in the VEGF-C group ( P<0.05). At 56 days after injury, the count of Iba1-positive microglia across all the above-mentioned regions was increased in the SCI group and negative control group ( P<0.01), compared with that in the sham group, whereas it was reduced in these regions in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.01). At 56 days after injury, TNF-α and IL-1β levels in these regions were both elevated in the SCI group and negative control group when compared with those in the sham group ( P<0.05), whereas they were reduced in the VEGF-C group, compared with those in the SCI group and negative control group ( P<0.05). At 56 days after injury, neuronal survival in the regions was decreased in the SCI group and negative control group, compared with that in the sham group ( P<0.05), whereas it was increased in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.05). Conclusion:SCI can induce secondary neuroinflammation and neuronal damage in remote brain regions by impairing the drainage function of MLVs.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.