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Yihong Tian,1,2,&ast; Yanyue Tan,3,&ast; Ming Yang,1 Xiayang Lv,3 Yunhao Zheng,1 Qiang Zhang,4 Yanyu Sun,1 Jun Wang,1,2 Xin Xiong1,2 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Orthodontics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Xin Xiong, West China Hospital of Stomatology, Sichuan University, No. 14 section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Email wangjunv@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aimed to thoroughly explore the relationship between individual oral behavior and the differing numbers of temporomandibular disorder (TMD) symptom in the general population.Methods: A total of 565 participants were recruited and completed a questionnaire containing demographic characteristics, eight specific oral behaviors, and five major TMD symptoms (5Ts) checklist. Multivariate linear regression analysis was performed to assess the relationship between individual oral behavior and the number of TMD symptoms, after controlling for confounders.Results: The prevalence of TMD symptoms was up to 38.2% in the general population, with 64.6% of the participants engaging in one or more oral behaviors. Female participants showed a stronger positive association with most oral behaviors than males. Moreover, wake oral behaviors exhibited a higher correlation coefficient value with TMD symptom number than sleep oral behaviors. Among the eight oral behaviors, bruxism in sleep exhibited no significant correlation with the of TMD symptom number (P> 0.05). Seven other specific oral behaviors were significantly correlated with the number of TMD symptoms by multivariate linear regression analysis (P< 0.01). The associations between the seven oral behaviors and TMD symptom number remained significant in sleep posture pressuring jaw (β: 0.165, 95% CI: 0.080– 0.250), bruxism in awake (β: 0.341, 95% CI: 0.132– 0.550), teeth clenching (β: 0.422, 95% CI: 0.264– 0.580), pressing, holding, or touching teeth together (β: 0.282, 95% CI: 0.169– 0.395), holding or tightening muscles without clenching (β: 0.447, 95% CI0.304– 0.589), holding jaw forward or to the side (β: 0.694, 95% CI0.526– 0.861), and holding jaw in rigid or tense position (β: 0.571, 95% CI0.418, 0.724) after adjustment for demographic factors (P< 0.01).Conclusion: There was a positive association between seven specific oral behaviors and TMD symptom number. Individuals with higher frequency of specific oral behaviors are more likely to suffer from more TMD symptoms. Sleep bruxism exhibited no association with TMD symptoms and symptom number.Keywords: oral behaviors, temporomandibular disorders, TMD symptom number, cross-sectional study

Shiya Zeng,1,&ast; Yanyue Tan,1,2,&ast; Zhiwei Cao,3 Yunhao Zheng,1 Tiqian Liu,1 Yifei Deng,1 Xin Xiong1 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Xiong, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 15, West Section 3, Second Ring Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 028 85501425, Email drxiongxin@scu.edu.cnObjective: Growing researches explore vitamin D’s role in temporomandibular disorders (TMDs), but the link between vitamin D and TMDs remains debated. To clarify the causal relationship, we conducted a Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS).Subjects and Methods: The GWAS dataset of vitamin D (GWAS ID: ukb-d-30890_irnt; sample size: 329247) was obtained from the IEU Open GWAS project. And that of TMDs (GWAS ID: finn-b-TEMPORO; sample size: 134280), initiated on August 25th, 2017 and publicly released on December 18th, 2023, was extracted from the FinnGen dataset, whose cases were diagnosed based on the revised International Classification of Diseases, 10th Edition (ICD-10) code K07.6. Both datasets were obtained from the European population. According to three assumptions of MR analysis, a bi-directional MR analysis was performed to measure the causal relationship, with Inverse variance weighted (IVW) as the primary method and MR Egger and Weighted median as supplement. Moreover, diverse sensitivity analyses, including Cochran’s Q test, MR Egger intercept, Mendelian randomized polymorphism RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis, were used to verify the stability of the findings.Results: The MR analysis supported causal effects of vitamin D levels on TMDs risks within the European population using IVW method [odds ratio = 1.316; 95% confidence interval = 1.086 to 1.595; P = 0.005], supported by MR Egger and Weighted median. While there was no indication that TMDs have a direct impact on vitamin D levels [β: − 0.00738, standard error = 0.00665; P = 0.568].Conclusion: The study revealed that within the European population higher levels of vitamin D led to higher risks of developing temporomandibular disorders, but found no obvious evidence that TMDs are causally associated with vitamin D. The conclusion should be cautiously interpreted, given the selection bias of TMDs patients sample.Keywords: Mendelian randomization analysis, temporomandibular joint disorders, vitamin D, 25-hydroxyvitamin D

Sophie Lau Rui Han,1,&ast; Jie Xiang,1,&ast; Xiang-Xiang Zeng,2 Pei-Di Fan,1 Qiao-Yu Cheng,1 Xue-Man Zhou,1 Zheng Ye,2 Xin Xiong,1 Jun Wang1 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Xiong; Jun Wang, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86-28-85503898 ; +86-28-85501425, Email drxiongxin@scu.edu.cn; wangjunv@scu.edu.cnPurpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation.Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p< 0.05 was considered statistically significant.Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008).Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.Keywords: temporomandibular disorder, temporomandibular joint pain, three-dimensional analysis, 3D slicer

Ruonan Sun,1,&ast; Shuyuan Zhang,1,&ast; Jiarui Si,2 Liming Zhang,1 Haolun Yang,1 Zheng Ye,1 Xin Xiong2 1West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zheng Ye, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Email zheng_ye@scu.edu.cn Xin Xiong, West China Hospital of Stomatology, Sichuan University, No. 14 Section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85503898, Email drxiongxin@scu.edu.cnBackground: Studies have reported correlations between various oral behaviors and painful temporomandibular disorders (TMD), yet comprehensive research on the independent effects of each oral behavior within the general population remains sparse.Objective: This cross-sectional study aimed to investigate the association between painful TMD (PT) and various oral behaviors in general population.Methods: A questionnaire survey was conducted with participants to collect data encompassing demographic characteristics, eight specific oral behaviors, and the 5 major TMD symptoms(5Ts) checklist. Participants were categorized into PT and non-PT (NPT) groups based on their responses to the 5Ts checklist. Those reporting TMJ/facial pain or headaches were assigned to the PT group, while all other participants constituted the NPT group. Both univariate and multivariate logistic regression analyses were employed to evaluate the association between individual oral behavior and the presence of PT, controlling for demographic confounders including age, sex, systemic diseases, and dental treatments history.Results: A total of 441 valid questionnaires were received, including 156 males and 285 females. The prevalence of PT was identified to be 33.33%, with 61.00% of participants engaging in one or more types of oral behaviors. Each oral behavior was more frequently reported in the PT group compared to the NPT group. The univariate logistic regression analysis identified positive correlations between all eight oral behaviors and PT. In the multivariate logistic regression analysis, these associations persisted after adjustment for demographic confounders including age, sex, history of systemic diseases and dental treatments (P< 0.01). The behaviors most strongly associated with PT were “Hold or jut jaw forward/to the side” (OR:4.478), “Hold, tighten or tense muscles without clench” (OR:3.343) and “Hold jaw in rigid or tense position” (OR:3.209).Conclusion: The presence of oral behaviors has significant association with PT. Individuals exhibiting multiple oral behaviors are more likely to experience PT. Additional studies are needed to clarify the effects of reducing oral behaviors on pain-related symptoms.Keywords: oral behaviors, painful temporomandibular disorders, Temporomandibular Joint, general population, cross-sectional study

Xianrui Song,1,&ast; Danyang Li,1,&ast; Lingling Gan,2,&ast; Xiyu Xiong,1 Aobo Nie,1 Huanhuan Zhao,3 Yunfeng Hu,1 Guangming Li,4 Jun Guo1 1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 2Experiment Center for Science and Technology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 3Basic Medical Experiment Center, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 4Department of Anesthesiology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Guo, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel +86 13813909055, Email guoj@njucm.edu.cn Guangming Li, Department of Anesthesiology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, People’s Republic of China, Email ligm7681@163.comIntroduction: Extracellular protein nanoparticles (PNs) and ions perform synergistical functions in the control of transmembrane osmotic pressure (OP) under isotonic conditions. Intravenous injection may disrupt the ion balance and alter PN levels in blood plasma, changing transmembrane OP and damaging vascular endothelial cells.Methods: Na ions were injected into AngII–induced HUVECs to simulate cell injury in vitro, and tail vein infusion of Na ions into hypertensive rats was performed to assess vascular damage. Optical measurements using an intermediate filament (IF) tension probe were conducted to detect indicators related to transmembrane OP. Immunofluorescence, Western blotting and small interfering RNA (siRNA) transfection were employed to investigate inflammasomes and the relationship between Abl2 and inflammation.Results: Electrolyte injections with sodium ions (but not glucose and hydroxyethyl starch) induced the production of ASC and NLRP3 inflammasomes in Ang II–induced HUVECs; this in turn resulted in the disorder of calcium signals, and changes in transmembrane OP and cell permeability. Moreover, injection of Na ions into Ang II–induced HUVECs activated the mechanosensitive protein Abl2, involved in inflammation-induced transmembrane OP changes. A drug combination was identified that could induce OP recovery and block hyperpermeability induced by cytoplasmic inflammatory corpuscles in vivo and in vitro.Conclusion: Changes in extracellular PNs and ions following chemical stimuli (Ang II) participate in the regulation of transmembrane OP. Furthermore, injection of Na ions causes vascular endothelial injury in Ang II-induced cells in vitro and hypertension rats in vivo, suggesting it is not safe for hypertensive patients, and we propose a new drug combination as a solution. Keywords: Na ion injection, vimentin tension probe, protein-nanoparticles, transmembrane OP, Ang II-induced vascular endothelial injury, Abl2

Dan Pu, Shiyong Zhang, Shoushan Hu, Yuyao Zhang, Xin Xiong, Shufang Du State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Shufang Du; Xin Xiong, Email dushufang@scu.edu.cn; drxiongxin@scu.edu.cnObjective: This study aims to investigate the relationship between oral health-related quality of life (OHRQoL) and emotional distress (ED), including anxiety and depression, in orthodontic patients.Methods: A cross-sectional study was conducted involving 603 orthodontic patients, consisting of 401 females (66.5%) with a mean age of 24.15 ± 7.72 and 202 males (33.5%) with a mean age of 24.16 ± 7.72. A questionnaire containing questions of demographic information, the Oral Health Impact Profile (OHIP-14) and the Huaxi emotional-distress index (HEI) was employed to assess OHRQoL and ED. According to the HEI score, the respondents were divided into ED group (HEI > 8) and non-ED group (HEI ≤ 8). Data were analyzed using Kolmogorov–Smirnov test, Mann–Whitney test and logistic regression analysis with the significance level set at p < 0.05.Results: The prevalence of poor OHRQoL and ED of the study sample was 28.4% and 19.57%, respectively. There was a significantly higher prevalence of ED among poor OHRQoL patients (35.67%) compared to those with good OHRQoL (13.19%) (p < 0.001). Poor OHRQoL and risky drinking behavior addressed higher significant correlation with ED patients than non-ED patients (p < 0.05). There were no statistical differences in other factors such as gender, age, and appliance type (p > 0.05). Poor OHRQoL orthodontic patients were at a higher risk of suffering from anxiety and depression compared to those with good OHRQoL (age-risky drinking behavior-sex-adjusted: OR = 4.00; all p < 0.001).Conclusion: Oral health-related quality of life (OHRQoL) is related to emotional stress. Namely, patients with poor OHRQoL are more likely to experience anxiety and depression. As a result, orthodontists should consistently assess the emotional well-being and OHROoL of patients over the treatment course for better treatment outcomes.Keywords: orthodontic patients, oral health-related quality of life, emotional distress, anxiety, depression, cross-sectional study

Jianv Wang,1,&ast; Hongye Liao,1,&ast; Jieming Ban,2 Sen Li,2 Xia Xiong,1 Qingqing He,1 Xinyu Shi,2 Hongping Shen,2 Sijin Yang,2 Changzhen Sun,2 Li Liu1 1Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changzhen Sun, Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel/Fax +86-136-9949-2406, Email sunchangzhen@swmu.edu.cn Li Liu, Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel/Fax +86-193-3860-9127, Email liuli@swmu.edu.cnBackground: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also have unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, and toxic side effects. As an effective biologic drug carrier, albumin combines with cyanine dyes to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues and are widely used in tumor imaging and photothermal therapy.Methods: Herein, a newly synthesized near-infrared dye IR-817 was combined with bovine serum albumin (BSA) to create BSA@IR-817 nanoparticles. Through the detection of fluorescence emission and absorption, the optimal concentration and ratio of BSA and IR-817 were determined. Subsequently, dynamic light scattering (DLS) measurements and scanning electron microscopy (SEM) were used for the physical characterization of the BSA@IR-817 nanoparticles. Finally, in vitro and in vivo experiments were conducted to assess the fluorescence imaging and photothermal therapeutic potential of BSA@IR-817 nanoparticles.Results: IR-817 was adsorbed onto the BSA carrier by covalent conjugation and supramolecular encapsulation, resulting in the formation of dispersed, homogeneous, and stable nanoparticles with a particle size range of 120– 220 nm. BSA@IR-817 not only improved the poor water solubility, fluorescence quenching, and toxic side effects of IR-817 but also enhanced the absorption and fluorescence emission peaks in the near-infrared region, as well as the fluorescence in the visible spectrum. In addition, BSA@IR-817 combined with laser 808 irradiation was able to convert light energy into heat energy with temperatures exceeding 50 °C. By creating a mouse model of subcutaneous melanoma, it was discovered that the tumor inhibition rate of BSA@IR-817 was greater than 99% after laser irradiation and that it achieved nearly complete tumor ablation without causing significant toxicity.Conclusion: Our research, therefore, proposes the use of safe and effective photothermal nanoparticles for the imaging, diagnosis, and treatment of melanoma, and offers a promising strategy for future biomedical applications.Keywords: albumin, cyanine dyes, near-infrared imaging, photothermal therapy, melanoma

Xin Xiong,1,2,&ast; Xinlin Gao,1,&ast; Jiawei Zhong,1 Shoushan Hu,1 Yijun Li,1 Yunhao Zheng,1 Yang Liu2 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China; 2State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, 610041, People’s Republic of China, Tel +86 028-85503898, Fax +86 018-85503898, Email liu@scu.edu.cnPurpose: This study conducted a bibliometric analysis that comprehensively described publications on temporomandibular joint and occlusion from 1 January 2000 to 31 October 2022, aiming to reveal hotspots and predict future research trends.Methods: A total of 2985 articles and reviews were retrieved from Web of Science Core Collection (WoSCC). Excel 2019, VOSviewer and CiteSpace software were used for visualizing analysis of research trends, authors, journals, institutions, countries, keywords and cited references.Results: Both the annual publication counts and citation times increased significantly. Wang MQ was the most active author. Moreover, Manfredini D and Okeson JP were the most influential two. Journal of Oral Rehabilitation was the core journal. University of Sao Paulo was the most productive institutions. “Temporomandibular disorders” (TMDs), “temporomandibular joint” and “occlusion” were the top 3 keywords with the most frequencies. Keywords and references with burst showed that the causes of TMDs, diagnosis and treatments for TMDs as well as bruxism may be hotspots currently and in the future.Conclusion: In this study, the research trends, the most productive and influential authors, journals, institutions, countries, in addition to keywords and cited references with burst in the field of temporomandibular joint and occlusion were revealed by a bibliometric analysis, which could help scholars to understand recent hotspots and future trends.Keywords: bibliometric analysis, temporomandibular joint, occlusion, keywords analysis

Yunhao Zheng,1 Rui Zhu,2 Chuqiao Xiao,3 Qiaoyu Cheng,3 Yifei Long,3 Xueman Zhou,3 Shilong Zhang,4 Jun Wang,3 Xin Xiong1,3 1Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xin Xiong, National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Tel/Fax +86-28-85503898, Email drxiongxin@scu.edu.cnPurpose: This study aims to explore the association of pressure pain thresholds (PPTs) with age, gender, and pain in patients with temporomandibular disorders (TMD).Patients and Methods: A total of 301 TMD patients (248 female and 53 male) were recruited and classified into the high and low age groups according to their median age of 26 years. Patients’ demographics, pain-related variables, TMD-related variables, and PPTs of both left and right temporomandibular joints (TMJs), masseter, and temporalis were collected.Results: Pain duration and visual analog scale of pain (VAS) showed no significant correlations with PPTs (P> 0.05). Multiple linear regression analysis revealed a significant positive association of PPTs of all six sites with males (β=0.41– 0.72 kg·cm− 2, 95% CI (0.19– 0.38, 0.74– 0.99), P< 0.001), as well as with the high age group [β=0.28– 0.36 kg·cm− 2, 95% CI (0.07– 0.20, 0.47– 0.53), P< 0.020]. Furthermore, PPTs of the left TMJ showed a significant negative association with left pain-related TMD (PT) [β=− 0.21 kg·cm− 2, 95% CI (− 0.38, − 0.04), P=0.026], but PPTs of the remaining sites did not show a significant association with PT (P> 0.05). Stratified analysis showed that PPTs in females were associated with the high age group [β=0.25– 0.37 kg·cm− 2, 95% CI (0.04– 0.20, 0.45– 0.56), P< 0.020] and that PPT of the left TMJ was associated with left PT [β=− 0.21 kg·cm− 2, 95% CI (− 0.39, − 0.03), P=0.043]. The remaining PPTs did not show a significant association with PT (P> 0.05). In males, PPTs did not show significant correlations with age, PT and VAS (P> 0.05).Conclusion: PPTs in the orofacial region are associated with gender and age in TMD patients. Pain duration and intensity show no significant correlations with PPTs in TMD patients. Researchers and dentists should take age and gender into account when using PPTs as auxiliary diagnostic indicators for PT.Keywords: pain sensitivity, temporomandibular disorders, pressure pain threshold, age, gender

Zheng Y, Zhu R, Xiao C, et al. J Pain Res. 2023;16:2205–2216. The authors have advised that they neglected to include a funding statement on page 2215 of the published paper. The funding statement should read as follows. Funding This work was supported by the Technology Innovation Project of Science and Technology Bureau of Chengdu (2022-YF05-01691-SN) and Clinical Research Project of West China Hospital of Stomatology, Sichuan University (LCYJ-2023-YY-2). The authors apologize for this error.

Felicia Forma,1 Tyler G Knight,2 Frances P Thorndike,1 Xiaorui Xiong,1 Rebecca Baik,2 Fulton F Velez,1 Yuri A Maricich,1 Daniel C Malone3 1Pear Therapeutics, Inc., Medical Affairs Department, Boston, MA, USA; 2Labcorp Drug Development, Market Access Consulting Department, Gaithersburg, MD, USA; 3Strategic Therapeutics, LLC, Oro Valley, AZ, USACorrespondence: Felicia Forma, Pear Therapeutics, Medical Affairs Department, 200 State St, Boston, MA, 02109, USA, Email felicia.forma@peartherapeutics.comBackground and Objectives: This analysis evaluated insomnia severity and long-term impact on healthcare resource utilization (HCRU) and costs after treatment with Somryst® (previously called SHUTi), a digital therapeutic delivering cognitive behavioral therapy for insomnia (CBT-I).Methods: Change from baseline in insomnia severity index (ISI) score was assessed using last observed ISI score. A pre/post analysis of claims data was conducted, comparing HCRU in patients with self-identified sleep problems who successfully initiated the therapeutic (index date) between June 1, 2016 and December 31, 2018.Results: A total of 248 patients were analyzed (median age 56.5 years, 57.3% female, mean ISI score 19.13, 52.4% treated with sleep aid medications pre-index). After 9 weeks, mean ISI score declined by 37.2% from baseline (19.1 vs 12.0), 58.8% of patients achieved ISI responder status (ISI score improved by => 7; NNT: 1.7), and 26.6% of patients achieved insomnia remission (ISI score < 8; NNT for remission: 3.8). After two-year follow-up, post-index events were reduced (compared to 2 years pre-index) for emergency department visits (− 53%; IRR: 0.47; 95% CI 0.27, 0.82; P=0.008), hospiatizations (-21%; IRR: 0.79; 95% CI 0.46, 1.35; P=0.389) and hospital outpatient visits (− 13%; IRR: 0.87; 95% CI 0.66, 1.14; P=0.315). Slightly increased rates were observed for ambulatory surgical center visits (2%; IRR: 1.02; 95% CI 0.73, 1.44; P=0.903) and office visits (2%; IRR: 1.02; 95% CI 0.92, 1.14; P=0.672). The number of patients treated with sleep aid medications dropped 18.5% (52.4% pre-index vs 42.7% post-index). Average number of prescriptions decreased from 3.98 pre-index to 3.73 post-index (P= 0.552). Total two-year cost reduction post-index vs pre-index was $510,678, or -$2059 per patient.Conclusion: In a real-world cohort of patients with chronic insomnia, treatment with a digital therapeutic delivering CBT-I was associated with reductions in insomnia severity, emergency department visits, and net costs.Keywords: CBT-I, cognitive behavioral therapy for insomnia, chronic insomnia, prescription digital therapeutic, SHUTi, Somryst

Yang H, Xiong X, Zhang L, Wu C, Liu Y. Int J Nanomedicine. 2011;6:2043–2051. An error during the preparation and figure assembly of Figure 7A on page 2049 led to the non-specific IgG group being inadvertently duplicated from the Control group. The correct version of Figure 7 is shown below. Figure 7 Continued. Figure 7 Adhesion of control microbubbles, VCAM-1-targeted microbubbles, and isotype control IgG microbubbles under low shear stress exposure of 6.3 dynes/cm2 for 3 minutes. (A) Representative bright field micrographs of microbubbles adhered to LPS-activated HUVEC-CS cells (magnification 40×). The insets are the high-magnification fields of the white dotted windows. (B) The adhered microbubble numbers on the HUVEC-CS cell monolayer were quantified by microbubble counting from six random microscopic fields (magnification 40×) for each group.Abbreviations: VCAM-1, vascular cell adhesion molecule 1; HUVEC-CS, human umbilical vein endothelial cells, subline.Notes: *P < 0.05 vs control (non-targeted microbubbles); **P < 0.01 vs control (non-targeted microbubbles) or non-specific IgG conjugated microbubbles. This correction has no impact to the findings of the study, and does not change any description, results or conclusions of the original paper. The authors apologize for this error.

Xiaozhou Fan,1 Yanli Guo,1 Luofu Wang,2 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1 1Department of Ultrasound, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Urology, Daping Hospital, Institute of Surgery Research, Third Military Medical University, Chongqing, People’s Republic of China Abstract: In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times (P>0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different (P

Xiaozhou Fan,1,* Luofu Wang,2,* Yanli Guo,1 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1 1Department of Ultrasound, Southwest Hospital, 2Department of Urology, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: Ultrasound (US)-targeted microbubble destruction has been widely used as an effective drug-delivery system. However, nanobubbles (NBs) have better stability and stronger penetration than microbubbles, and drug delivery assisted by US-targeted NB destruction (UTND) still needs to be investigated. Our aim was to investigate the effect of doxorubicin (DOX) on the inhibition of prostate cancer growth under UTND. Contrast-enhanced US imaging of transplanted PC3 prostate cancer in mice showed that under a combination of 1 W/cm2 US power and a 100 Hz intermittent pulse with a “5 seconds on, 5 seconds off” mode, NBs with an average size of (485.7±33) nm were effectively destroyed within 15 minutes in the tumor location. PC3 cells and 20 tumor-bearing mice were divided into four groups: a DOX group, a DOX + NB group, a DOX + US group, and a DOX + NB + US group. The cell growth-inhibition rate and DOX concentration of xenografts in the DOX + NB + US group were highest. Based on another control group and these four groups, another 25 tumor-bearing mice were used to observe the treatment effect of nine DOX injections under UTND. The xenografts in the DOX + NB + US group decreased more obviously and had more cellular apoptosis than other groups. Finally, electron microscopy was used to estimate the cavitation effect of NBs under US irradiation in the control group, NB group, US group, and NB + US group. The results of scanning electron microscopy showed that PC3 cells in the DOX + NB + US group had more holes and significantly increased cell-surface folds. Meanwhile, transmission electric microscopy confirmed that more lanthanum nitrate particles entered the parenchymal cells in xenografts in the NB + US group compared with the other groups. This study suggested that UTND technology could be an effective method to promote drugs to function in US-irradiated sites, and the underlying mechanism may be associated with a cavitation effect. Keywords: ultrasound therapy, nanobubble, cavitation effect, prostate cancer

Hong Yang, Xiaoyan Xiong, Lie Zhang, Chunhui Wu, Yiyao LiuDepartment of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of ChinaAbstract: The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, microbubbles with a specific ligand to receptors expressed at the site of specific diseases are constructed. The present study aimed to engineer a novel type of bio-functionalized microbubbles (vascular cell adhesion molecule 1 [VCAM-1]-targeted microbubbles), and determine whether VCAM-1-targeted microbubbles exhibit specific adhesion to lipopolysaccharide (LPS)-activated endothelial cells. Our data showed that VCAM-1expression was significantly upregulated in both LPS-activated endothelial cells in vitro and endothelium in a rat atherosclerosis model in vivo. Targeted microbubbles were designed by conjugating anti-VCAM-1 monoclonal antibodies to the shell of microbubbles using biotin–avidin bridging chemistry methods. Microbubble adhesion to endothelial cells was assessed in a flow chamber at two shear stress conditions (6.3 and 10.4 dynes/cm2). Our data showed that microbubble adhesion depends on both the surface anti-VCAM-1 antibody densities and the exposed shear stresses. Adhesion of VCAM-1-targeted microbubbles onto LPS-activated endothelial cells increased with the surface antibody densities, and decreased with the exposed shear stresses. These findings showed that the specific ligand-carrying microbubbles have considerable potential in targeted ultrasound molecular imaging or ultrasound-assisted drug/gene delivery applications.Keywords: targeted microbubbles, VCAM-1, adhesion, HUVEC-CS, shear flow