Aim or purpose: To detect central metabolic differences in temporomandibular disorders (TMDs) induced by occlusal disorder and psychological stress, thereby clarifying relevant etiological diagnoses. Materials and methods: This study was approved by the institutional ethics committee. Male Sprague-Dawley (SD) rats were used to establish models of TMDs induced by occlusal disorder and psychological stress. The success of modeling was evaluated through body weight measurement, behavioral experiments, micro-CT scanning of the condyle, and histological staining of condylar tissue. Micro-PET/CT scanning was employed to analyze metabolic differences in central nuclei between the two etiological types of TMDs, and immunofluorescence staining was used for pathological validation. Results: A significant decrease in central glucose metabolism was observed in TMDs rats induced by occlusal disorder and psychological stress. Moreover, there was a substantial difference between the two groups in the right frontal association cortex and right cingulate cortex, with the psychological stress group exhibiting lower glucose metabolism. Additionally, immunofluorescence staining for the astrocyte-specific marker glial fibrillary acidic protein (GFAP) revealed a decrease in GFAP expression in the target brain regions of both groups, with a more pronounced reduction in the psychological stress group. Conclusions: Occlusal disorder and psychological stress lead to heterogeneity in brain nucleus activity in TMDs rats, indicating differences in cerebral glucose metabolism between the two etiological types of TMDs. This finding may provide new strategies for the etiological diagnosis of TMDs in the future.

Amelogenin has been widely used in clinical practice for periodontal bone regeneration. However, the precise mechanism underlying its osteogenic effects remains incompletely understood. In this study, we hypothesized that amelogenin enhances periodontal bone regeneration by facilitating the migration and homing of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs were used to evaluate the cell migration promoting ability of amelogenin by the Transwell test. Immunofluorescence was performed to assess the beta-catenin nuclear translocation following amelogenin treatment. To investigate amelogenin-induced cell homing in vivo, we established a green fluorescent protein (GFP)-labeled bone marrow transplantation model using BALB/c mice transgenic for GFP. The migratory effects of amelogenin were examined in this model, with Wnt3a, a Wnt/β-catenin pathway activator, serving as a positive control. Subsequently, cell homing and bone regeneration were evaluated through a fluorescence microscope, micro-CT, hematoxylin and eosin (H&E), and Masson staining. In vitro Transwell assays demonstrated that amelogenin significantly enhanced BMMSC migration, with effects comparable with Wnt3a, a canonical Wnt/β-catenin pathway activator. Immunofluorescence analysis revealed pronounced nuclear translocation of β-catenin in BMMSCs following a 24-h amelogenin treatment. Notably, these effects were abolished by a Wnt/β-catenin pathway inhibitor, confirming the pathway's involvement. In GFP-labeled bone marrow-transplanted mice, amelogenin treatment significantly increased GFP+ cell recruitment to the bone defect site, mirroring the effects of Wnt3a. Micro-CT and histological (H&E) analyses further demonstrated that both amelogenin and Wnt3a accelerated bone regeneration compared with untreated controls. Crucially, this regenerative effect was suppressed upon Wnt/β-catenin pathway inhibition, reinforcing the mechanistic link between amelogenin and β-catenin-mediated osteogenesis. Amelogenin and Wnt3a promoted periodontal bone regeneration both in vitro and in vivo by enhancing BMMSC migration through Wnt/β-catenin signaling activation.

Pain is the most common adverse effect of orthodontic treatment. Transient receptor potential vanilla-like protein 4 (TRPV4) plays an important role in pain regulation, and central amygdala (CeA) is also an important nuclear mass in pain regulation, but there is a paucity of literature on the roles of TRPV4 in CeA on tooth movement pain. C57BL/6 J mice were divided into control group, 0 g group and 30 g group. After establishing the experimental tooth movement model, behavioral tests were first performed, which showed that pain behavior peaked on day 1 and then dropped to baseline on day 7. The 30 g group developed anxiety-like behavior after 14 days of application, and the degree increased over time. In addition, immunofluorescence staining and western blot was performed on CeA tissues. The results showed that tooth movement significantly increased the fluorescence intensity of TRPV4 and protein expression of TRPV4, NLRP3, P65 and the phosphorylation of P65 proteins in CeA. Administration of TRPV4 antagonists in CeA through intraperitoneal injection effectively alleviated tooth movement induced pain and anxiety-like behaviors. This suggests that TRPV4 within CeA may mediate the regulation of tooth movement pain through NLRP3-NF-κB signaling pathway, which not only clarify the mechanism of CeA regulating tooth movement pain, but also help regulating tooth movement pain precisely.

Periodontal ligament stem cells (PDLSCs) have broad applications in tissue engineering and regeneration. However, the function of PDLSCs changes in different microenvironments. This study aimed to explore the effects of different developmental stages on the biological characteristics of PDLSCs. Here, PDLSCs were successfully cultured from the periodontal tissues of various groups, including a group with immature roots, a young group with mature roots, and an aging group with mature roots. By comparing the results of the three experimental groups, we found that the donors with immature roots exhibited the best proliferative ability and osteogenic differentiation, whereas the aging group demonstrated the worst proliferation. The trend for adipogenic differentiation was the opposite to that for osteogenic differentiation. The cell sheet and in vivo experiments revealed that in the immature root group, the cells produced more extracellular matrix and new bone and better absorbed the implant materials. These results indicate that PDLSCs perform various functions at different stages of development. In clinical applications of PDLSCs for periodontal regeneration, donors with incompletely developed roots have stronger biological characteristics.

Osteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent drug release behavior. We demonstrate that the hydrogel can withstand 28000 loading-unloading mechanical cycles and exhibits fast shape memory at body temperature (30 s) with the potential for minimally invasive surgery. We find that the hydrogel can also alleviate the inflammatory reaction and regulate oxidative stress in situ to establish a microenvironment conducive to healing. We show that the sequential release of tannic acid and Kartogenin can promote the migration of bone marrow mesenchymal stem cells into the hydrogel scaffold, followed by the induction of chondrocyte differentiation, thus leading to full-thickness cartilage regeneration in vivo. This work may provide a promising solution to address the problem of cartilage regeneration.

目的 探究临床医学本科皮肤性病学教学中实施信息化教学法的应用价值.方法 2022 年 2-6 月,选择 2018 级临床医学专业本科生 110 名,以"班级"做分组处理,组别记为对照组与观察组,前者开展传统教学模式,纳入学生 54 名,后者实行信息化技术教学模式,纳入学生 56 名;评估两组学生考核成绩(课后阶段测试成绩和期末总成绩)、评判性思维能力、教学效果、教学满意度并展开组间对比.结果 观察组学生课后阶段测试(系统性红斑狼疮、银屑病、梅毒、天疱疹)成绩均较对照组学生高,同时期末理论考试成绩明显高于对照组学生,差异有统计学意义(P＜0.05).观察组学生教学前评判性思维能力(Chinese Version of Critical Thinking Disposition Inventory,CTDI-CV)评分比较,差异无统计学意义(P＞0.05).观察组教学后CTDI-CV(寻找真相、分析能力、评判性思维的信心、求知欲、认知成熟度)评分均明显高于对照组,差异有统计学意义(P＜0.05).观察组教学效果(职业价值-态度-行为和伦理、交流技能、医学科学基础知识、临床技能、群体健康和卫生系统、判定性思维和研究、信息管理)评分较对照组显著高,且教学满意度较对照组明显高,差异有统计学意义(P＜0.05).结论 实施信息化教学法在临床医学本科皮肤性病学教学中,不仅有助于提高学生理论知识水平,并培养其评判性思维能力,同时提高整体教学效果,取得满意的教学结果 .

Objective Keloid is a kind of disfiguring pathological scarring specific to human skin. For various cutaneous and internal tumours, 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) is a curative choice, and we explored its mechanism on keloid fibroblast (KFB) proliferation and invasion via regulating forkhead box protein O6 (FoxO6) antioxidant stress. Methods Human keloid fibroblasts (HKFs) were cultured in vitro, treated with 5-ALA-PDT and simultaneously transfected with overexpression plasmid (oe-FoxO6). HKF proliferation, invasion, apoptosis and cell cycle were assessed by CCK-8/Transwell/TUNEL/flow cytometry assays. The protein levels of Bax, Bcl-2, FoxO6, Cyclin D1, Cyclin A1 and Cyclin B1 were determined by Western blot. SOD and CAT activities, and MDA and ROS levels were examined using the kits. Results Pretreatment of 5-ALA-PDT prominently inhibited the proliferation of HKFs, up-regulated Bax level, down-regulated Bcl-2 level, promoted HKF apoptosis, and notably inhibited HKF invasion. 5-ALA-PDT treatment decreased the expression of FoxO6 protein, promoted oxidative stress in HKFs, up-regulated ROS and MDA levels in HKFs and reduced SOD and CAT antioxidant enzyme activities. In addition, 5-ALA-PDT pretreatment increased the level of cell cycle-associated protein Cyclin D1, decreased the levels of Cyclin A1 and Cyclin B1, and accelerated cell cycle arrest in the G 0 /G 1 phase of HKFs. Overexpression of FoxO6 partially annulled the promoting effects of 5-ALA-PDT on G 0 /G 1 phase cell cycle arrest and oxidative stress in HKFs and enhanced cell proliferation and invasion. Conclusion 5-ALA-PDT limited HKF proliferation and invasion by down-regulating the expression of FoxO6.

目的 探究多次传代对牙周膜干细胞(periodontal ligament stem cells,PDLSCs)成骨分化的影响,以及牙周炎症来源牙周膜干细胞成骨相关长链非编码RNA(osteogenesis impairment-related long noncoding RNAs of periodontal mesenchymal stem cells from periodontitis patients,lncRNA POIR)对多次传代后PDLSCs成骨分化功能的影响.方法 将PDLSCs细胞连续传代,取第3代、第15代、第30代细胞用于后续实验.碱性磷酸酶(alkaline phosphatase,ALP)染色、ALP活性和茜素红染色检测不同代数PDLSCs成骨分化能力.实时定量聚合酶链式反应(real-time polymerase chain reaction,RT-PCR)检测不同代数细胞lncRNA POIR表达水平.将第30代PDLSCs分为3组:空白对照组、无义序列转染对照组(转染sh-NC质粒)和lncRNA POIR下调组(转染sh-lncRNA POIR质粒).ALP染色、ALP活性和茜素红染色检测各组PDLSCs成骨分化能力.RT-PCR、Western blot检测各组PDLSCs中矮小相关转录因子2(runt-related transcription factor 2,Runx2)、ALP、骨钙素(osteocalcin,OCN)表达水平.采用生物信息学分析lncRNA POIR和微小RNA-214(miR-214)的结合位点.为进一步确定lncRNA POIR与miR-214之间调控关系,RT-PCR检测lncRNA POIR下调组与对照组PDLSCs中miR-214表达水平的差异,从而评价lncRNA POIR对miR-214的作用.结果 与第3代和第15代比较,第30代PDLSCs成骨结节形成量减少(P<0.05),ALP染色面积占比减少(P<0.01),ALP活性降低(P<0.01).与第3代和第15代比较,第30代PDLSCs中lncRNA POIR的表达水平下降(P<0.01).与空白对照组和无义序列转染对照组比较,lncRNA POIR下调组PDLSCs成骨结节形成减少(P<0.01),ALP染色面积占比减少(P<0.01),ALP活性降低(P<0.05).与空白对照组和无义序列转染对照组比较,lncRNA POIR下调组PDLSCs中Runx2、ALP、OCN表达水平降低(P<0.05).生物信息学分析结果显示lncRNA POIR与miR-214存在结合位点.与空白对照组和无义序列转染对照组比较,lncRNA POIR下调组miR-214的表达水平升高(P<0.01).结论 多次传代会损害PDLSCs的成骨分化功能,抑制lncRNA POIR表达.lncRNA POIR可以调控PDLSCs传代过程中的成骨分化功能.

目的:探讨脂肪间充质干细胞(hASCs)对小鼠创面组织超氧化物歧化酶(SOD)及血清血管内皮生长因子(VEGF)、表皮生长因子(EGF)和碱性成纤维细胞生长因子(bFGF)表达的影响.方法:选取24只裸鼠建立创面损伤模型后分为三组,实验组给予基底膜基质(Matrigel)复合hASCs注射治疗,细胞组给予hASCs注射治疗,对照组给予磷酸液缓冲液(PBS)注射治疗,记录创面愈合情况.结果:所有裸鼠都造模成功,无动物因麻醉或手术而死亡.与对照组相比,实验组与细胞组术后7 d与14 d的创面愈合率、创面组织的SOD水平显著升高(均P<0.05),而丙二醛(MDA)水平显著降低(P<0.05).与对照组相比,实验组与细胞组术后14 d的血清VEGF、EGF及bFGF表达水平显著升高(均P<0.05),且实验组与细胞组对比差异有统计学意义(均P<0.05).MASSON染色结果为实验组创面完全愈合,表皮修复情况良好,可见部分炎性细胞浸润,呈复层上皮排列;细胞组已修复部分的表皮修复情况良好,表皮呈复层上皮排列,仍有部分创面未能愈合,肉芽组织生长良;对照组尚未愈合的创口周围可见有瘢痕组织增生,可见炎性细胞浸润较明显,仍有相当一部分创面尚未能愈合.结论:Matrigel复合hASCs在小鼠创面中的应用能促进细胞因子的分泌,抑制创面的氧化应激作用,从而促进创面愈合.

目的:研究骨髓间充质干细胞(BMSCs)联合曲安奈德治疗对兔耳增生性瘢痕形成的影响,以及对创面巨噬细胞极化的影响.方法:60只新西兰兔随机均分为模型组、曲安奈德组和联合治疗组,所有兔均在耳部建立1 cm×1 cm创面.创面建立第21天,模型组不予任何治疗,曲安奈德组在兔耳创面瘢痕内多点注射曲安奈德,联合治疗组在曲安奈德组治疗的基础上在兔耳创面瘢痕内注射BMSCs进行治疗.记录三组兔耳创面愈合和完全上皮化时间,测量创面瘢痕面积和突出高度、瘢痕指数并进行比较.实时荧光定量PCR法检测创面瘢痕炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素质1β(IL-1β)、白细胞介素6(IL-6)和单核细胞趋化蛋白(MCP-1)]和巨噬细胞表面标志物[自然杀伤细胞表达的表面受体(CD16)、诱导性一氧化氮合酶(iNOS)、巨噬细胞甘露糖受体(CD206)和精氨酸酶1(Arg1)]表达水平并比较.结果:三组兔耳创面愈合时间比较无统计学差异(均P>0.05),曲安奈德组兔耳创面完全上皮化时间、创面瘢痕面积和突出高度均显著低于模型组,而显著高于联合治疗组(均P<0.05).曲安奈德组兔耳创面瘢痕炎症因子(TNF-α、IL-1β、IL-6和MCP-1)和M1巨噬细胞表面标志物(CD16和iNOS)表达水平均显著低于模型组,而显著高于联合治疗组(均P<0.05).曲安奈德组兔耳创面瘢痕M2巨噬细胞表面标志物(CD206和Arg1)表达水平均显著高于模型组,而显著低于联合治疗组(均P<0.05).结论:BMSCs联合曲安奈德对兔耳增生性瘢痕的形成具有抑制作用,其机制可能与促进M2巨噬细胞极化,降低瘢痕的炎症反应有关.

目的 探究不同照射强度的低能量激光(low-level laser therapy,LLLT)对衰老牙周膜干细胞(periodontal ligament stem cells,PDLSCs)增殖和成骨分化功能的影响.方法 将PDLSCs分为yPDLSCs组(年轻组,15～25岁,男3例,女3例,共10颗牙)和aPDLSCs组(老年组,40～55岁,男3例,女3例,共8颗牙).待上述两组PDLSCs长至80％左右融合率时将细胞分为5组:yPDLSCs组(年轻组)、aPDLSCs对照组(老年对照组)、aPDLSCs 4 J/cm2组、aPDLSCs 8 J/cm2组和aPDLSCs 16 J/cm2组,yPDLSCs组和aPDLSCs对照组不予以激光照射,其余3个实验组分别以4,8,16 J/cm2 LLLT处理aPDLSCs细胞,隔天照射1次,每次照射20 s,共照射3次.克隆形成实验检测各组细胞的增殖能力.茜素红染色检测各组细胞成骨结节形成量,碱性磷酸酶(ALP)活性检测细胞ALP活性.RT-PCR法检测细胞矮小相关转录因子2(runt-related transcription factor 2,Runx2)、ALP、骨钙素(osteocalcin,OCN)表达水平.ELISA法检测细胞TNF-α分泌量.结果 与aPDLSCs对照组比较,4 J/cm2组和8 J/cm2组aPDLSCs的克隆形成率明显升高(P<0.05),16 J/cm2组细胞的克隆形成率变化无统计学意义;与yPDLSCs组相比,aPDLSCs对照组克隆形成率明显下降(P<0.01).与aPDLSCs对照组比较,4 J/cm2组和8 J/cm2组aPDLSCs的成骨结节形成明显增多(P<0.05),16 J/cm2组aPDLSCs的成骨结节形成减少(P<0.05);与yPDLSCs组相比,aPDLSCs对照组的成骨结节形成量减少(P<0.01).与aPDLSCs对照组比较,8 J/cm2组aPDLSCs中ALP活性明显升高(P<0.01),16 J/cm2组aPDLSCs中ALP活性降低(P<0.01);与yPDLSCs组相比,aPDLSCs对照组ALP活性降低(P<0.01).与aPDLSCs对照组比较,8 J/cm2组aPDLSCs的成骨相关基因Runx2、ALP、OCN表达水平明显升高(P<0.01),16 J/cm2组aPDLSCs中Runx2、ALP、OCN表达水平变化无统计学意义;与yPDLSCs组相比,aPDLSCs对照组的成骨相关基因表达水平下降(P<0.01).与aPDLSCs对照组比较,4 J/cm2组和8 J/cm2组aPDLSCs中TNF-α的分泌明显减少(P<0.05),16 J/cm2组aPDLSCs中TNF-α的分泌量变化无统计学意义;与yPDLSCs组相比,aPDLSCs对照组TNF-α的分泌量明显升高(P<0.01).结论 适宜强度LLLT可提高衰老PDLSCs的增殖能力和成骨分化能力.

Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease of the joint. The early manifestations of TMJ-OA are abnormal remodeling of condylar subchondral bone. In bone tissue, bone marrow mesenchymal stem cells (BMSCs) and osteoblasts play important roles in the differentiation and maturation of most hematopoietic cells. MicroRNA-26b (miR-26b) is upregulated during the osteogenesis of BMSCs, and miR-26b overexpression leads to the activation of β-catenin and the enhancement of osteogenesis and cartilage formation. However, the pathologic mechanism remains unclear. In the present study, we used a rat model with OA-like changes in the TMJ induced by experimental unilateral anterior crossbite (UAC) and found that the level of miR-26b was markedly lower in BMSCs from the subchondral bones of UAC rats than in those from sham control rats. MiR-26b overexpression by agomiR-26b increased condylar subchondral bone osteogenesis in UAC rats. Notably, although agomiR-26b primarily affected miR-26b levels in the subchondral bone (but not in cartilage or the synovium), the overexpression of miR-26b in BMSCs in UAC rats largely rescued OA-like cartilage degradation, while the inhibition of miR-26b in BMSCs exacerbated cartilage degradation in UAC rats. We measured the expression levels of β-catenin and related osteogenic and osteoclastic factors after using miR-26b mimics and inhibitors in vivo. Moreover, BMSCs were treated with the β-catenin blocker Wnt-C59 and then transfected with miR-26b mimics or inhibitors. Then, we examined the expression of β-catenin as the direct target of miR-26b. The results of the present study indicate that miR-26b may modulate subchondral bone loss induced by abnormal occlusion and influence the osteogenic differentiation of subchondral BMSCs through β-catenin in the context of TMJ-OA progression.

Recent studies have shown that the incidence of chronic primary pain including temporo-mandibular disorders (TMD) and fibromyalgia syndrome (FMS) often exhibit comorbidities. We recently reported that central sensitization and descending facilitation system contributed to the development of somatic pain hypersensitivity induced by orofacial inflammation combined with stress. The purpose of this study was to explore whether TMD caused by unilateral anterior crossbite (UAC) can induce somatic pain hypersensitivity, and whether the cholecystokinin (CCK) receptor -mediated descending facilitation system promotes hypersensitivity through neuron-glia cell signaling cascade. UAC evoked thermal and mechanical pain hypersensitivity of the hind paws from day 5 to 70 that peaked at week 4 post UAC. The expression levels of CCK1 receptors, interleukin-18 (IL-18) and IL-18 receptors (IL-18R) were significantly up-regulated in the L4 to L5 spinal dorsal horn at 4 weeks post UAC. Intrathecal injection of CCK1 and IL-18 receptor antagonists blocked somatic pain hyper-sensitivity. IL-18 mainly co-localized with microglia, while IL-18R mainly co-localized with astrocytes and to a lesser extent with neurons. These findings indicate that the signaling transduction between neurons and glia at the spinal cord level contributes to the descending pain facilitation through CCK1 receptors during the development of the comorbidity of TMD and FMS.Perspective: CCK1 receptor-dependent descending facilitation may mediate central mechanisms underlying the development of widespread somatic pain via a reciprocal neuron-glial signaling cas-cade, providing novel therapeutic targets for the clinical treatment of TMD and FMS comorbidities.(c) 2022 by United States Association for the Study of Pain, Inc.

目的 利用新一代16S rDNA全长测序技术比较银屑病患者与健康人的肠道菌群多样性和细菌表型差异.方法 纳入12例银屑病患者,以12例正常人作为健康对照,测序分析粪便样品中细菌群落的结构组成和表型特征.结果 银屑病患者肠道菌群的多样性指数较健康人显著降低(P＜0.05),肠道菌群的结构组成明显区别于健康人.在菌门水平上,Firmicutes和Proteobacteria分别在对照组和患者组中高度富集(P＜0.05).从菌科到菌种水平上,6个菌科、8个菌属以及6个菌种的相对丰度在患者组和对照组之间存在显著差异(P＜0.05).细菌表型的分析结果显示,患者组中厌氧型细菌的相对丰度显著降低(P＜0.01),兼性厌氧型细菌的相对丰度显著升高(P＜0.05),细菌对氧化胁迫的耐受性以及细菌生物膜的形成能力增强(P＜0.05).结论 银屑病患者肠道菌群的多样性较健康人显著降低,其菌落结构和多种细菌表型都发生了明显改变,肠道菌群失调可能是导致银屑病发病的重要原因之一.

目的:通过对鞘内注射和皮下注射两种给药方式的比较,探讨唑来膦酸对骨癌痛大鼠的镇痛效应及其可能机制.方法:将Walker 256乳腺癌细胞注入雌性SD大鼠胫骨以建立骨癌痛模型,单次或者持续给予唑来膦酸后,比较鞘内和皮下两种给药方式对大鼠痛行为学的影响.采用RT-PCR、Western blot和免疫荧光染色的实验方法观察脊髓背角IBA-1的改变情况.采用旷场实验和转棒实验观察唑来膦酸两种给药方式对大鼠运动功能和自发活动功能的影响.结果:单次或连续鞘内或皮下注射唑来膦酸均可显著改善大鼠热痛敏反应(P<0.05),并且鞘内注射的镇痛效应强于皮下注射(P<0.05).RT-PCR、免疫荧光染色和West-ern blot结果表明,持续鞘内注射唑来膦酸7天后,骨癌痛大鼠脊髓背角表达增高的IBA-1被显著抑制(P<0.05),而皮下注射并无此抑制效应(P>0.05).唑来膦酸的两种给药方式均未影响大鼠的运动功能和自发活动功能(P>0.05).结论:相比皮下注射,鞘内注射唑来膦酸在大鼠骨癌痛模型中表现出更强的镇痛效应,而抑制脊髓小胶质细胞的活化可能是其镇痛机制之一,此外,唑来膦酸在两种给药方式中均未表现出明显的神经毒副作用.

目的 探讨巴瑞替尼在骨癌痛大鼠模型中的镇痛效应及其对脊髓背角星形胶质细胞活化的影响.方法 按照体重将雌性SD大鼠随机分为3组:正常组、模型组与实验组,各10只.大鼠骨髓腔注射Walker 256细胞建立骨癌痛模型;正常组注射等量生理盐水.建模后第6天开始,实验组大鼠灌胃巴瑞替尼0.25μg·g-1,每天1次,连续7 d,模型组及正常组则灌胃等量生理盐水.用动物行为学实验方法检测大鼠干预前后机械缩足阈值(PWT)和热缩足反射潜伏期(PWL)变化,用免疫荧光染色法和蛋白质印迹法测定大鼠脊髓胶质纤维酸性蛋白(GFAP)的表达变化(灰度值).用酶联免疫吸附实验(ELISA)检测大鼠炎性因子的表达变化.结果 正常组、模型组和实验组在12 d的PWT分别为(14.38±1.77),(2.63±1.19)和(10.50±1.77)g;此3组在12 d的PWL分别为(16.24±1.22),(3.04±0.75)和(12.38±1.02)s;此3组的脊髓GFAP相对表达量分别为1.01±0.03,2.43±0.22和1.63±0.16;此3组的脊髓IL-1β含量分别为(87.36±5.34),(346.35±14.56)和(161.59±11.29)ng·g-1;此3组的脊髓IL-6含量分别为(134.97±7.49),(491.74±19.71)和(192.68±13.88)ng·g-1;此3组的脊髓TNF-α含量分别为(96.76±6.95),(528.26±21.68)和(247.74±14.93)ng·g-1.上述指标:模型组与正常组比较,或实验组与模型组比较,差异均有统计学意义(均P<0.05).结论 巴瑞替尼可有效减轻大鼠骨癌痛反应,其机制可能与抑制脊髓星形胶质细胞活化有关.

Temporomandibular disorders (TMD) are a group of diseases in the oral and maxillofacial region that can manifest as acute or chronic persistent pain, affecting millions of people worldwide. Although hundreds of studies have explored mechanisms and treatments underlying TMD, multiple pathogenic factors and diverse clinical manifestations make it still poorly managed. Appropriate animal models are helpful to study the pathogenesis of TMD and explore effective treatment measures. At present, due to the high cost of obtaining large animals, rodents and rabbits are often used to prepare TMD animal models. Over the past decade, various animal models have been intensively developed to understand neurobiological and molecular mechanisms of TMD, and seek effective treatments. Although these models cannot carry out all clinical features, they are valuable in revealing the mechanisms of TMD and creating curative access. Currently, there are multitudinous animal models of TMD research. They can be constructed in different means and summarized into four ways according to the various causes and symptoms, including chemical induction (intra-articular injection of ovalbumin, collagenase, formalin, vascular endothelial growth factor, intramuscular injection of complete Freund's adjuvant, etc.), mechanical stress stimulation (passive mouth opening, change of chewing load), surgical operation (partial disc resection, joint disc perforation) and psychological stress induction. Here, we summarize and discuss different approaches of animal models for determining neurophysiological and mechanical mechanisms of TMD and assess their advantages and limitations, respectively.

The treatment of diabetic chronic wounds remains a global challenge due to the up-regulated inflammation response, oxidant stress, and persistent infection during healing process. Developing wound dressing materials with ideal biocompatibility, adequate mechanical strength, considerable under-water adhesion, sufficient anti-inflammation, antioxidant, and antibacterial properties is on-demand for clinical applications. In this study, we developed a bioactive skin-mimicking hydrogel band-aid through the combination of tannic acid (TA) and imidazolidinyl urea reinforced polyurethane (PMI) (TAP hydrogel) and explored its potentials in various medical applications, including hemostasis, normal skin incision, full-thickness skin wounds, and bacterial-infection skin incision on diabetic mice. TA was loaded into PMI hydrogel network to enhance the mechanical properties of TAP hydrogels through multiple non-covalent interactions (break strength: 0.28–0.64 MPa; elongation at break: 650–930%), which could resist the local stress and maintain the structural integrity of wound dressings during applications. Moreover, owing to the promising moisture-resistant adhesiveness and organ hemostasis, outstanding anti-inflammation, antibacterial, and antioxidant properties, TAP hydrogels could efficiently promote the recovery of skin incision and defects on diabetic mice. To further simulate the practical situation and explore the potential in clinical application, we also verified the treatment efficiency of TAP hydrogel in S. aureus-infected skin incision model on diabetic mice.