Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To explore the effect of the defect area and volume of intra-articular impacted fragments (IAIF) on the contact stress of the ankle joint surface.Methods:A 23-year-old male volunteer, 168 cm in height and 60 kg in weight, with no history of trauma or anatomic abnormality of the ankle, was selected. On the basis of a normal ankle finite-element model, IAIF-defect finite-element models were established. The first group consisted of IAIF-defect models with identical area but different volumes: on the distal tibial articular surface the defect area was 4 mm × 5 mm (20 mm 2), and the heights were 2 mm, 3 mm, 4 mm, 5 mm and 6 mm. The second group consisted of IAIF-defect models with identical defect volume but different areas. The defect volume was 90 mm 3, while the defect areas on the distal tibial articular surface were 2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm, and 5 mm×6 mm, with corresponding heights of 15 mm, 10 mm, 6 mm, 5 mm, and 3 mm. Under a 600 N vertical load the contact stress of the ankle joint was calculated, and the finite-element data were recorded and analyzed. Pearson correlation analysis was used to analyze, separately for the two groups, the correlation between IAIF defect and the maximum contact stress (MCS) of the distal tibial articular surface, and simple linear regression analysis was performed to obtain regression equations. Equivalence zero testing was used to verify the correlations and to compare their differences. Results:For IAIF defects with the same area but different volumes, including 4 mm×5 mm×2 mm, 4 mm×5 mm×3 mm, 4 mm×5 mm×4 mm, 4 mm×5 mm×5 mm, and 4 mm× 5 mm×6 mm, the corresponding maximum contact stress (MCS) on the distal tibial joint surface were 3.846 MPa, 3.839 MPa, 3.835 MPa, 3.833 MPa, and 3.831 MPa, respectively, with an average of 3.837 MPa. The mean ±1% range is from 3.799 MPa to 3.875 MPa. The correlation analysis showed that the IAIF defects with the same area but different volumes were negatively correlated with contact stress ( r=-0.956, P=0.011). The linear regression equation was MCS=-0.0002×VI+3.851, where VI denotes IAIF volume. Equivalence zero testing confirmed that all measured values lay within the predefined ±1 % margin, satisfying the equivalence null hypothesis. For IAIF defects of identical volume (90 mm 3) but varying articular surface areas—2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm and 5 mm×6 mm—the corresponding MCS values were 2.147 MPa, 2.812 MPa, 3.622 MPa, 4.476 MPa and 6.186 MPa, respectively (mean 3.849 MPa; equivalence band 3.811-3.887 MPa at ±1% of the mean). Correlation analysis demonstrated a strong positive relationship between identical-volume varying-area IAIF defects and contact stress ( r=0.996, P<0.001). The linear regression equation was MCS=0.168×AI+1.236, where AI denotes IAIF area. Equivalence zero testing indicated that none of the measured values fell within the predefined ±1% margin, failing to satisfy the equivalence null hypothesis. Conclusion:In posterior ankle fractures, the volume change of IAIF defects has no clinical significance in relation to MCS, showing a small negative correlation. However, the area change of IAIF defects is clinically significant in relation to MCS, demonstrating a larger positive correlation.

BACKGROUND:In the occurrence and development of demyelinating diseases of the central nervous system,neuroinflammation caused by microglia is the main pathological feature,so inhibiting the inflammatory response is very important to alleviate demyelination.Hydroxysafflor yellow A can protect the blood-brain barrier,inhibit neuronal apoptosis,and improve neurological function.OBJECTIVE:To explore the mechanism of hydroxysafflor yellow A inhibiting bicyclohexanone oxalyl dihydrazone-induced demyelination in mice.METHODS:(1)In vivo:Thirty healthy male C57BL/6 mice were randomly divided into three groups:normal group,cuprizone group,and hydroxysafflor yellow A group.The mice in the cuprizone group and the hydroxysafflor yellow A group were fed with 0.2％cuprizone diet for 6 weeks to establish mouse models of demyelination.The mice in the normal group were fed with normal diet.At the end of the 4th week,the mice in the hydroxysafflor yellow A group were intraperitoneally injected with hydroxysafflor yellow A 20 mg/kg per day.The mice in the normal and cuprizone groups were intraperitoneally injected with normal saline for 2 weeks.The behavioral changes of mice were evaluated by open field test and elevated plus maze test.The loss of myelin sheath in corpus callosum was detected by black gold staining,myelin basic protein and degraded myelin basic protein immunofluorescence staining.The activation of microglia and the expression of inflammatory factors were detected by I ba-1 immunofluorescence staining and ELISA,respectively.The protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 in the brain of mice in each group were detected by western blot assay.(2)In vitro experiment:The inflammation model of BV2 microglia was established by lipopolysaccharide induction.BV2 cells were divided into normal group,lipopolysaccharide group(1 μg/mL),and lipopolysaccharide(1 μg/mL)+hydroxysafflor yellow A(25 μmol/L)group.The expression levels of tumor necrosis factor α and interleukin 6 in the supernatant were detected by ELISA.RESULTS AND CONCLUSION:(1)Compared with the normal group,the mice in the cuprizone group had severe anxiety,abnormal autonomic movement ability,and a large amount of myelin sheath loss in the corpus callosum.The average fluorescence intensity of myelin basic protein was significantly reduced,and the average fluorescence intensity of degraded myelin basic protein was significantly increased.The number of lba1+microglia increased,the contents of interleukin 1β,tumor necrosis factor α,and interleukin 6 in the brain increased,and the protein expression levels of Toll-like receptor 4,myeloid differentiation factor 88,and nuclear factor κB p65 increased significantly.The above symptoms and indexes of mice were reversed after hydroxysafflor yellow A treatment.(2)Hydroxysafflor yellow A significantly inhibited the expression of inflammatory factors such as tumor necrosis factor α,and interleukin 6 induced by lipopolysaccharide in BV2 microglia.(3)The above results demonstrate that hydroxysafflor yellow A can significantly improve cuprizone-induced demyelination in mice.The mechanism of action is related to the inhibition of microglial activation-mediated inflammatory response through the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor κB p65 signaling pathway.

Objective To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.Methods A total of 130 mice were randomly divided into a cecal ligation and puncture(CLP)group(n=100)and a Sham group(n=30)Mouse model of sepsis was established with CLP procedure.Flow cytometry was used to analyze the proportions of peripheral blood CD4+T and CD8+T cells and programmed cell death protein 1(PD-1)positive T cell subsets in mice.Bacterial colonization in organs such as the heart,liver and kidneys was quantified by plating homogenates of the organs.Pathological changes in immune organs were observed with HE staining.The expression and localization of CD4?,CD8?,and PD-1?cells in immune organs were detected with immunohistochemical staining,and Image J software was employed for subsequent quantification of the number of the positive cells.Results HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression.Compared with the Sham mice,the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood(P<0.05),notably in the liver,which showed the most severe infection.In the CLP group,the proportion of CD4+T lymphocytes in peripheral blood at days 1,3,and 5 postoperatively was decreased by 56%,70.57%,and 87.42%,respectively,when compared with the Sham group(P<0.001).The proportion of CD8+T lymphocytes was decreased by 48.33%relative to the Sham group only at day 5(P<0.001).In contrast,the proportion of CD4+T cell subsets expressing PD-1 was increased to 673.08,423.08,and 600 times that of the Sham group,respectively,at the same postoperative time points(P<0.001).Immunohistochemical results showed that,in the CLP group,the proportion of CD4+T cells in the thymus,spleen,and mesenteric lymph nodes was increased to 7.65,2.66,and 3.7 times that of the Sham group,respectively,at the early-stage peak(P<0.001),and then these proportions were decreased by 82.8%(P<0.001),41.9%(P<0.01),and 60.15%(P<0.001),respectively,at the late-stage trough when compared with the early-stage peak in the corresponding organs.The proportion of CD8+positive cells was increased in the early stage and then decreased insignificantly,while the proportion of PD-1+positive cells was increased continuously,and reached 6.24,13.9,and 20.96 times that of the Sham group at the peak in the thymus,spleen,and mesenteric lymph nodes respectively(P<0.001),with their expression regions showing a rough overlap with those of CD4+cells.Conclusion During sepsis,the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4?T lymphocytes,leading to declined defenses against infection,which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

The coil adverse events in the U.S.Food and Drug Administration Manufacturer and User Facility Device Experience(MAUDE)database from January 2021 to June 2024 were analyzed retrospectively.The risks of coils during the clinical application and their causes were explored with hospital survey and expert demonstration in Shandong Province.Some improving measures were put forward for the safe use of coils,including implementing the main responsibility of the registrant,enhancing the professional skills of the using institutions and strengthening the supervision of the supervisory authorities.[Chinese Medical Equipment Journal,2025,46(6):83-87]

BACKGROUND:The reduction of contact area,edge load,and stress increase of adjacent cartilage caused by knee cartilage defect are considered to easily cause degenerative changes in this tissue,which may develop into knee osteoarthritis.Growth factors are considered to be a treatment method to promote the healing of damaged cartilage and delay the progression of degenerative arthritis.OBJECTIVE:To analyze the hotspots and prospects of growth factor-promoted knee cartilage regeneration research by bibliometric methods.METHODS:The first author retrieved 321 articles related to growth factor-promoted knee cartilage regeneration research from the Web of Science core set database.VOSviewer 1.6.19 software was used to analyze the publication volume,country,institution,keyword,and literature citation status of the articles,and investigate the research hotspots.RESULTS AND CONCLUSION:(1)From 2000 to 2024,the annual number of publications in the field of growth factor-promoted knee cartilage regeneration showed an overall upward trend,with the highest number of publications in 2021.Harvard University in the United States published the most papers.(2)Keyword analysis showed that the frequency of keywords such as growth factor,cartilage,cartilage repair,platelet-rich plasma,and cartilage regeneration was high.In addition,the keyword co-occurrence network diagram showed that growth factor was closely related to keywords such as cartilage repair and cartilage regeneration,indicating that growth factor research plays an important role in the field of cartilage regeneration.(3)The results of literature citation analysis showed that the combination of platelet-rich plasma and muscle-derived stem cells may provide a new and effective treatment strategy for patients with osteoarthritis,which can deepen the understanding of cartilage repair mechanisms by promoting stem cell proliferation and cartilage formation.Fibroblast growth factor 2,fibroblast growth factor 18,and insulin growth factor 1 play a key role in cartilage repair and can promote chondrocyte proliferation and matrix synthesis.In particular,fibroblast growth factor 18 can promote the repair of damaged cartilage,thereby alleviating patients'pain and dysfunction,which deserves further in-depth study in the future.The latest research has developed a new Polyhedrin Delivery System(PODS)that can continuously release growth factors such as bone morphogenetic protein 2 and 7,significantly promoting chondrocyte proliferation and cartilage repair.This system provides a new perspective and potential therapy for the treatment of osteoarthritis.(4)Therefore,bone morphogenetic protein 2,7,insulin growth factor 1,and recombinant human fibroblast growth factor 18 are promising growth factor therapies for promoting cartilage regeneration.In the future,further in-depth research on the mechanism of action of growth factors,optimization of treatment strategies,and strengthening of long-term efficacy and safety evaluation are needed.

BACKGROUND:The reduction of contact area,edge load,and stress increase of adjacent cartilage caused by knee cartilage defect are considered to easily cause degenerative changes in this tissue,which may develop into knee osteoarthritis.Growth factors are considered to be a treatment method to promote the healing of damaged cartilage and delay the progression of degenerative arthritis.OBJECTIVE:To analyze the hotspots and prospects of growth factor-promoted knee cartilage regeneration research by bibliometric methods.METHODS:The first author retrieved 321 articles related to growth factor-promoted knee cartilage regeneration research from the Web of Science core set database.VOSviewer 1.6.19 software was used to analyze the publication volume,country,institution,keyword,and literature citation status of the articles,and investigate the research hotspots.RESULTS AND CONCLUSION:(1)From 2000 to 2024,the annual number of publications in the field of growth factor-promoted knee cartilage regeneration showed an overall upward trend,with the highest number of publications in 2021.Harvard University in the United States published the most papers.(2)Keyword analysis showed that the frequency of keywords such as growth factor,cartilage,cartilage repair,platelet-rich plasma,and cartilage regeneration was high.In addition,the keyword co-occurrence network diagram showed that growth factor was closely related to keywords such as cartilage repair and cartilage regeneration,indicating that growth factor research plays an important role in the field of cartilage regeneration.(3)The results of literature citation analysis showed that the combination of platelet-rich plasma and muscle-derived stem cells may provide a new and effective treatment strategy for patients with osteoarthritis,which can deepen the understanding of cartilage repair mechanisms by promoting stem cell proliferation and cartilage formation.Fibroblast growth factor 2,fibroblast growth factor 18,and insulin growth factor 1 play a key role in cartilage repair and can promote chondrocyte proliferation and matrix synthesis.In particular,fibroblast growth factor 18 can promote the repair of damaged cartilage,thereby alleviating patients'pain and dysfunction,which deserves further in-depth study in the future.The latest research has developed a new Polyhedrin Delivery System(PODS)that can continuously release growth factors such as bone morphogenetic protein 2 and 7,significantly promoting chondrocyte proliferation and cartilage repair.This system provides a new perspective and potential therapy for the treatment of osteoarthritis.(4)Therefore,bone morphogenetic protein 2,7,insulin growth factor 1,and recombinant human fibroblast growth factor 18 are promising growth factor therapies for promoting cartilage regeneration.In the future,further in-depth research on the mechanism of action of growth factors,optimization of treatment strategies,and strengthening of long-term efficacy and safety evaluation are needed.

The coil adverse events in the U.S.Food and Drug Administration Manufacturer and User Facility Device Experience(MAUDE)database from January 2021 to June 2024 were analyzed retrospectively.The risks of coils during the clinical application and their causes were explored with hospital survey and expert demonstration in Shandong Province.Some improving measures were put forward for the safe use of coils,including implementing the main responsibility of the registrant,enhancing the professional skills of the using institutions and strengthening the supervision of the supervisory authorities.[Chinese Medical Equipment Journal,2025,46(6):83-87]

Objective:To explore the effect of the defect area and volume of intra-articular impacted fragments (IAIF) on the contact stress of the ankle joint surface.Methods:A 23-year-old male volunteer, 168 cm in height and 60 kg in weight, with no history of trauma or anatomic abnormality of the ankle, was selected. On the basis of a normal ankle finite-element model, IAIF-defect finite-element models were established. The first group consisted of IAIF-defect models with identical area but different volumes: on the distal tibial articular surface the defect area was 4 mm × 5 mm (20 mm 2), and the heights were 2 mm, 3 mm, 4 mm, 5 mm and 6 mm. The second group consisted of IAIF-defect models with identical defect volume but different areas. The defect volume was 90 mm 3, while the defect areas on the distal tibial articular surface were 2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm, and 5 mm×6 mm, with corresponding heights of 15 mm, 10 mm, 6 mm, 5 mm, and 3 mm. Under a 600 N vertical load the contact stress of the ankle joint was calculated, and the finite-element data were recorded and analyzed. Pearson correlation analysis was used to analyze, separately for the two groups, the correlation between IAIF defect and the maximum contact stress (MCS) of the distal tibial articular surface, and simple linear regression analysis was performed to obtain regression equations. Equivalence zero testing was used to verify the correlations and to compare their differences. Results:For IAIF defects with the same area but different volumes, including 4 mm×5 mm×2 mm, 4 mm×5 mm×3 mm, 4 mm×5 mm×4 mm, 4 mm×5 mm×5 mm, and 4 mm× 5 mm×6 mm, the corresponding maximum contact stress (MCS) on the distal tibial joint surface were 3.846 MPa, 3.839 MPa, 3.835 MPa, 3.833 MPa, and 3.831 MPa, respectively, with an average of 3.837 MPa. The mean ±1% range is from 3.799 MPa to 3.875 MPa. The correlation analysis showed that the IAIF defects with the same area but different volumes were negatively correlated with contact stress ( r=-0.956, P=0.011). The linear regression equation was MCS=-0.0002×VI+3.851, where VI denotes IAIF volume. Equivalence zero testing confirmed that all measured values lay within the predefined ±1 % margin, satisfying the equivalence null hypothesis. For IAIF defects of identical volume (90 mm 3) but varying articular surface areas—2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm and 5 mm×6 mm—the corresponding MCS values were 2.147 MPa, 2.812 MPa, 3.622 MPa, 4.476 MPa and 6.186 MPa, respectively (mean 3.849 MPa; equivalence band 3.811-3.887 MPa at ±1% of the mean). Correlation analysis demonstrated a strong positive relationship between identical-volume varying-area IAIF defects and contact stress ( r=0.996, P<0.001). The linear regression equation was MCS=0.168×AI+1.236, where AI denotes IAIF area. Equivalence zero testing indicated that none of the measured values fell within the predefined ±1% margin, failing to satisfy the equivalence null hypothesis. Conclusion:In posterior ankle fractures, the volume change of IAIF defects has no clinical significance in relation to MCS, showing a small negative correlation. However, the area change of IAIF defects is clinically significant in relation to MCS, demonstrating a larger positive correlation.