Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.

Objective:To investigate the impact of central screw size on the stability of the glenoid baseplate in reverse shoulder arthroplasty using a finite element analysis.Methods:Four sizes of central screws (length × diameter) were designed: 25.0 mm×5.5 mm (G1), 30.0 mm×5.5 mm (G2), 25.0 mm×6.5 mm (G3), and 30.0 mm×6.5 mm (G4), along with a glenosphere, a baseplate, and peripheral screws. The central screw of group G1 was selected for a biomechanical test along with a set of customized prosthesis. The results were used to validate a finite element model. The validated finite element model was employed to analyze the central screws of 4 different sizes under a vertically downward 490 N load in simulation. After the model calculation was completed, the total displacement of each model, the maximum Von Mises stress on the bone surface at the baseplate-bone contact interface, the maximum Von Mises stress on the bone tissue around the screw-bone interface, the maximum value of the maximum principal strain (tensile strain), the maximum value of the minimum principal strain (compressive strain), the total volume of bone damage, and the volume of bone damage around the central screw were analyzed.Results:Insignificant differences were found in the total displacement and total volume of bone damage across the 4 models. On the bone surface at the baseplate-bone contact interface, the maximum Von Mises stress in G3 and G4 (11.26 MPa and 9.88 MPa, respectively) was slightly higher than that in G1 and G2 (9.11 MPa and 8.90 MPa, respectively). On the bone tissue around the screw-bone interface, G4 exhibited significantly higher maximum stress (15.82 MPa) and significantly higher maximum value of the maximum principal strain (10.09×10 -2) than G1 (8.51 MPa, 3.88×10 -2), G2 (9.45 MPa, 4.29×10 -2), and G3 (9.92 MPa, 3.92×10 -2), while the maximum value of the minimum principal strain in G3 (12.12×10 -2)was significantly higher than that in G1 (8.23×10 -2), G2 (8.10×10 -2), and G4 (8.34×10 -2). The volume of bone damage around the central screw in G3 (11.4 mm 3) was significantly smaller than that in G1 (24.9 mm 3), G2 (28.5 mm 3), and G4 (20.3 mm 3). Conclusions:In reverse shoulder arthroplasty, to a certain extent, increasing the length of a central screw amplifies bone damage volume around the screw. Conversely, increasing only the diameter of a central screw reduces bone damage volume around the screw, consequently lowering the loosening risk of a central screw.

Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.

Objective:To investigate the impact of central screw size on the stability of the glenoid baseplate in reverse shoulder arthroplasty using a finite element analysis.Methods:Four sizes of central screws (length × diameter) were designed: 25.0 mm×5.5 mm (G1), 30.0 mm×5.5 mm (G2), 25.0 mm×6.5 mm (G3), and 30.0 mm×6.5 mm (G4), along with a glenosphere, a baseplate, and peripheral screws. The central screw of group G1 was selected for a biomechanical test along with a set of customized prosthesis. The results were used to validate a finite element model. The validated finite element model was employed to analyze the central screws of 4 different sizes under a vertically downward 490 N load in simulation. After the model calculation was completed, the total displacement of each model, the maximum Von Mises stress on the bone surface at the baseplate-bone contact interface, the maximum Von Mises stress on the bone tissue around the screw-bone interface, the maximum value of the maximum principal strain (tensile strain), the maximum value of the minimum principal strain (compressive strain), the total volume of bone damage, and the volume of bone damage around the central screw were analyzed.Results:Insignificant differences were found in the total displacement and total volume of bone damage across the 4 models. On the bone surface at the baseplate-bone contact interface, the maximum Von Mises stress in G3 and G4 (11.26 MPa and 9.88 MPa, respectively) was slightly higher than that in G1 and G2 (9.11 MPa and 8.90 MPa, respectively). On the bone tissue around the screw-bone interface, G4 exhibited significantly higher maximum stress (15.82 MPa) and significantly higher maximum value of the maximum principal strain (10.09×10 -2) than G1 (8.51 MPa, 3.88×10 -2), G2 (9.45 MPa, 4.29×10 -2), and G3 (9.92 MPa, 3.92×10 -2), while the maximum value of the minimum principal strain in G3 (12.12×10 -2)was significantly higher than that in G1 (8.23×10 -2), G2 (8.10×10 -2), and G4 (8.34×10 -2). The volume of bone damage around the central screw in G3 (11.4 mm 3) was significantly smaller than that in G1 (24.9 mm 3), G2 (28.5 mm 3), and G4 (20.3 mm 3). Conclusions:In reverse shoulder arthroplasty, to a certain extent, increasing the length of a central screw amplifies bone damage volume around the screw. Conversely, increasing only the diameter of a central screw reduces bone damage volume around the screw, consequently lowering the loosening risk of a central screw.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

This study aims to review the biomarkers of depression discovered by proteomic techniques to guide the identification of specific biomarkers for depression. Depression is a common psychological disease， and its diagnosis and efficacy evaluation rely on subjective clinical evaluation， lacking objective diagnostic tools. Proteomics is the primary method to discover and verify biomarkers. This study reviews proteomic biomarkers in brain tissue， cerebrospinal fluid and blood of patients with depression， as well as the latest strategies for screening biomarkers of depression.

Objective To assess the clinical efficacy and safety of fire needling therapy for vitiligo. Method A self-control study was carried out. Fifty-six vitiligo patients with 124 skin lesions were allocated by long-axis random to two groups. The treatment group received fire needling therapy weekly for 12 times or until cure and the control group, no treatment as a blank control. The clinical efficacy and safety were assessed after the completion of treatment. Result The total efficacy rate of local fire needling therapy for vitiligo skin lesions was 79.8% and there was a statistically significant difference as compared with the control group (P<0.05). The therapeutic effect was better in patients with faciocervical skin lesions or short course of disease. The therapeutic effect increased with an increase in the course of treatment at the early stage of treatment but did not significantly increase after 8 weeks of treatment. Main adverse reactions were mild pain and skin infection. Conclusion Local fire needling has a definite therapeutic effect on vitiligo with high safety.

Objective To study the influence of pregnant rats' prenatal chronic stress (PS) on learning and memory of their offspring rats and its possible molecular mechanisms.Methods Pregnant females were individually restrained for 45 min 3 times a day during pregnancy from day 14 to day 21.Control pregnant females were left undisturbed in their home cages.The rat offsprings were randomly assigned to PS group or control group.Males and females were kept for the study separately.The learning and memory of the developing rat offspring in the Morris water maze were examined.The basal levels of corticosterone (COR) and adreno-cortico-tropic-hormone (ACTH) were analyzed by using radioimmunoassay.The Golgi-Cox impregnation technique was used to compare density and morphology of the CA1 hippocampal dendritic spines.Results The escape latency (EL) to find the platform in the control group was significantly less than that in the PS group in female rat offspring (F =4.533,P ＜ 0.05),and the difference was statistically significant on the 5th day (t =2.788,P ＜ 0.01).EL to find the platform in the control group was significantly less than that in the PS group in male rat offspring (F =6.101,P ＜0.05),and the difference was statistically significant on the second day (t =3.051,P ＜ 0.01).In the space exploration experiments of the water maze,the retention time observed for the control group and the PS group in the goal quadrant was similar(P ＞ 0.05).The basal levels of the serum COR in the PS group were higher than those in the control group of female rat offspring(t =3.658,P ＜ 0.01) and the basal levels of the serum ACTH in the PS group were higher than those in the control group of male rat offsprings(t =2.319,P ＜ 0.05).A simplified pattern was observed in the CA1 hippocampal dendritic spines in the PS group,showing a less extent of dendritic arborization and the density was significantly lower than that in the control group(t =-3.072,P ＜ 0.01).Conclusions Altered function of the hypothalamic-pituitary-adrenal axis in the offspring mediates the cognitive alterations observed following prenatal stress should to be associated with the lower density and simplified pattern of CA1 dendritic spines.

Objective To investigate the effects of 4-aminosalicylic acid (4-ASA) on rats with 2,4,6-trinitrobenzenesulfonic acid-induced colitis in order to understand its mechanisms in treatment of inflammatory bowel disease (IBD). Methods Thirty SD rats were given 2,4,6-trinitrobenzenesulfonic acid to induce colitis and were divided into model group, 5-ASA (200 mg/kg) treated group and 4-ASA (200 mg/kg) treated group with 10 each. Another 10 rats were severed as normal control. Seven days later,all animals were sacraficed for estimation of colonic tissues. The iNOS and serum level of interleukin (IL)-8 were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) ,respectively. And the apoptosis of polymorphonuclear neutrophil (PMN) was examined by flow cytometry. Results In comparison with model group, the body weight was increased in rats treated with 4-ASA (t= 14.09,P<0.01), whereas the macroscopic and histological scores and MPO activity were decreased (t=7.87,18.37,6.66 and 19.60,respectively, all P values <0.01), which were similar to 5-ASA treated group (all P values > 0. 05). The expression of tissue iNOS was 73.55%±5.15% in model group, which was higher than that in control group [(5.95±1.45)% ,t=39.93,P<0.01)],but was lower than that in 5-ASA treated group [(37.80±3.82)%,t = 17.62,P<0.01] and 4-ASA treated group [(42.27±3.52) %, t= 15.76 ,P<0.01]. The serum level of IL-8 in model group was significantly higher than that in 5-ASA treated group and 4-ASA treated group (P<0. 01). The apoptosis of PMN in model group was lower than that in control group (t= 11.48,P<0.01), but higher than that in 5-ASA treated group (t= 7.51, P<0.01) and 4-ASA treated group (t= 10.47,P<0.01). Conclusions The efficacy of 4-ASA in treatment of IBD may be related to the mechanisms of reducing the migration and the activities of PMN, up-regulating PMN apoptosis and scavenging reactive oxygen radicals produced by PMN.