The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective:To explore the characteristic of dynamic function network connectivity (dFNC) of resting brain networks in internet gaming disorder (IGD) adolescents.Methods:Forty-four adolescent IGD subjects (IGD group, male/female: 38/6) and fifty healthy controls (HC group, male/female: 40/10) were collected, and the subjects completed demographic questionnaires, Young internet addiction scale(YIAS), Chinese adolescents' maladaptive cognitions scale(CAMAS), and functional magnetic resonance imaging (fMRI) tests. The fMRI data were preprocessed on the Matlab platform, and the preprocessed data was divided into 64 components for group level independent component analysis.The dynamic functional connectivity of obtained 18 effective independent components was analyzed by sliding time window technique, and the difference of dynamic functional connectivity of brain triple network between the IGD group and HC group was compared using SPSS 22.0 software.Results:Four repeated dFNC states were identified through cluster analysis.Each state indicated that different functional networks had different connection strengths.State 3, the most frequent state, had been indicated that the whole brain network of the subject was in a state of weak functional connectivity.The second frequent state was state 1, which indicated enhanced functional connectivity within the subject's central executive network (CEN).State 2 had been indicated enhanced functional connectivity within the subject's salience network (SN).State 4 had been indicated generally enhanced functional connectivity in the subjects' brain networks, and this state was the least frequent.The results of non-parametric permutation test on the time attribute showed that compared with the HC group, the IGD group had a longer time score (IGD group: 0.24±0.19, HC group: 0.13±0.15, t=1.19, P<0.05, non-parametric substitution test) for state 1 with strong connectivity within the CEN, which was positively correlated with the YIAS score and game time ( r=0.418, P=0.003; r=0.515, P=0.004).Compared with HC group, the functional connectivity of ICD group between the internal insula of the SN and the dorsal anterior cingulate cortex was enhanced ( P<0.05, FDR corrected), while the average residence time in weakly connected state 3 was longer ( Z=2.09, P<0.05, nonparametric substitution test). Conclusions:The difference in dynamic functional connectivity of the triple network in the brain of IGD adolescents under resting state is mainly manifested by strong connections in CEN, functional connections between insula and dorsal anterior cingulate cortex in SN is enhanced, and weakening of overall functional connections, which may play an important role in the pathological mechanism of IGD.

Objective:To construct and validate a risk prediction model for major complications 30 days after surgery in the elderly patients with hip fracture.Methods:A retrospective study was conducted to analyze the clinical data of 276 elderly patients with hip fracture who had been admitted to Department of Trauma and Orthopaedics, The Hospital Affiliated to Chengde Medical University from June 2019 to December 2021. There were 96 males and 180 females with an age of (74.5±9.3) years, and 139 femoral neck fractures and 137 intertrochanteric fractures. The outcome of this study was whether major complications occurred within 30 days after surgery. Multiple logistic regression analysis identified the risk factors for major complications in the elderly patients with hip fracture within 30 days after surgery. The forward step-by-step method and likelihood ratio test were used to screen the best prediction model. A nomogram was constructed to display the model. The stability and effectiveness of the model were evaluated by the receiver operating characteristic curve (ROC), Hosmer-Lemeshow goodness-of-fit test, clinical decision curve and clinical impact curve analysis.Results:Logistic regression analysis showed that decreased preoperative hemoglobin ( P< 0.05), time from admission to surgery >72 hours ( OR=3.001, 95% CI: 1.564 to 5.758, P<0.001), control of nutritional status (CONUT) score >4 points ( OR=3.394, 95% CI: 1.724 to 6.680, P<0.001), and age-adjusted modified frailty index (aamFI) >2 points ( OR=2.875, 95% CI: 1.548 to 5.339, P= 0.001), increased operation time ( OR=1.016, 95% CI: 1.006 to 1.025, P=0.001), and surgical bleeding >60 mL ( OR=2.373, 95% CI: 1.016 to 5.540, P=0.046) were independent risk factors for major complications within 30 days after surgery in the elderly patients with hip fracture. The area under the ROC curve in the logistic risk prediction model was 0.846 (95% CI: 0.799 to 0.889), and the results of Hosmer-Lemeshow goodness-of-fit test showed ( χ2=8.080, P=0.426). The clinical decision curve and clinical impact curve showed that the prediction model was accurate and effective. Conclusion:Based on the patients' preoperative hemoglobin, time from admission to surgery, control of nutritional status score, age-adjusted modified frailty index, operation time and surgical blood loss, this study has constructed successfully a risk prediction model for complications 30 days after surgery in the elderly patients with hip fracture which enables medical staff to predict the occurrence of major postoperative complications.

Objective:To explore the heterogeneity among keloids before and after radiotherapy and identify the changes of key cell subpopulations and their interactions utilizing single cell RNA sequencing technology.Methods:Four patients provided a total of 12 samples, each consisting of keloid tissue before and after radiotherapy and the normal skin tissue adjacent to the untreated keloid. The keloid was divided into left and right sides from the midline, and the left-side keloid was fractionally irradiated with 20 Gy electron beam in total in 4 consecutive days. The right-side keloid was irradiated with 10 Gy in 2 fractions before surgery and 10 Gy in 2 fractions after surgery.Results:A total of 25 573 fibroblasts were analyzed and categorized into nine subgroups (fibroblasts 1-9). The proportion of fibroblast-2 increased after radiotherapy ( t=4.70, P<0.05). The number of classical monocytes and macrophages increased after radiotherapy, but there was no significant difference due to the shorter time of sample taking at 2 d after radiotherapy ( P>0.05). Macrophages (4 723 cells) were further divided into four categories. CellPhoneDB analysis showed that type-3 macrophages interacted significantly more closely with fibroblasts than type-1 and type-2 macrophages. The most prominent signaling pathways for the interactions between type-3 macrophages and major fibroblast subtypes were the collagen signaling pathway and the chemerin signaling pathway. These interactions were more pronounced in the keloid samples after radiotherapy. Conclusions:The interactions between type-3 macrophages and fibroblasts (such as fibroblast-2) may serve as an important point for future studies on radio-sensitization of keloids.

AIM:This study aims to investigate the histopathological and ultrastructural alterations in the lung tissues of rats induced by a single intratracheal administration of bleomycin,with the objective of establishing a reliable model for future applications.METHODS:Six to eight-week-old SD rats were randomly allocated into two groups:the control group and the model group(n=12).Pulmonary fibrosis was induced in the rat models by a single intratracheal in-stillation of bleomycin(3 mg/kg),while an equivalent volume of saline was administered to the control group.The rats were executed on the 42nd day.Twelve rats remained in the control group,while nine rats remained in the model group.Lung tissue imaging was conducted using CT scans.Lung function tests were performed to assess changes in forced vital capacity(FVC)and dynamic lung compliance(Cdyn).Lung stiffness was determined through Young's modulus testing using a rheometer.The pathological structure of lung tissues was examined using both HE and Masson staining methods.Additionally,transmission electron microscopy was employed to evaluate collagen deposition in lung tissues,alveolar type Ⅱ epithelial cells,macrophages,and ultrastructural changes of the respiratory membrane.RESULTS:CT scans revealed honeycomb patterns in the lungs of model rats,along with partial bronchiectasis/bronchiectasis.In comparison to the con-trol group,the model group exhibited significantly lower FVC and Cdyn values,while lung stiffness were increased.HE and Masson staining demonstrated that rats in the model group exhibited alveolar structure destruction,alveolar septum thickening,inflammatory cell infiltration,and collagen deposition in alveolar septum.Transmission electron microscopy revealed several abnormalities in the model group:increased collagen fibers in the alveolar septa,misalignment of micro-villi in alveolar type Ⅱ epithelial cells,wrinkled nuclei with increased heterochromatin,swollen cytoplasmic mitochon-dria,fractured or haphazardly structured mitochondrion cristaes,and a significant decrease in their number(P＜0.05).Furthermore,lamellar bodies were vacuolated and reduced in number(P＜0.05),and dilated endoplasmic reticulums with degranulation were observed.There was an increase in alveolar macrophages and interstitial macrophages(P＜0.01).The respiratory membrane displayed structural disruptions and an increase in thickness(P＜0.01).CONCLUSION:Bleomycin induces decreased lung compliance,alveolar epithelial injury,alveolar septum thickening,collagen deposi-tion,and an increase in interstitial macrophages,ultimately resulting in pulmonary fibrosis in rats.

Objective:To explore the speech features of female patients with anhedonic depression and their recognition of pleasure deficient symptoms.Methods:A total of 102 female depression patients who were hospitalized at Nanjing Brain Hospital from September 2020 to October 2021 were selected, including 62 anhedonic depression patients (anhedonic group) and 40 non-anhedonic depression patients (non-anhedonic group). A total of 50 female healthy controls were recruited during the same period.All participants were evaluated by the 17-item Hamilton depression scale (HAMD-17), Snaith-Hamilton pleasure scale (SHAPS), and the temporal experience of pleasure scale (TEPS), as well as voice acquisition.SPSS 23.0 software was used for data processing.Statistical analysis was conducted using one-way ANOVA, non-parametric tests, Logistic regression, and receiver operating characteristic curve.Results:Compared with the non-anhedonic group, the anhedonic group showed significant changes in 15 voice features(all P<0.05), including Mel-frequency cepstral coefficients, formant frequencies, intensity, and energy features.Among these features, Mel-frequency cepstral coefficients exhibited the highest accuracy in identifying anhedonic depression, with sensitivity of 47.5%, specificity of 91.9%, area under curve (AUC) of 0.751, 95% CI=0.686-0.866.Formant frequencies could identify female anhedonic depression, with a sensitivity of 90.0%, a specificity of 40.3%, an AUC of 0.647, and 95% CI=0.605-0.824.Energy features could identify anhedonic deficient depression, with a sensitivity of 60.0%, a specificity of 74.2%, an AUC of 0.679, and 95% CI=0.587-0.804.Intensity features could identify female anhedonic depression, with a sensitivity of 70.0%, a specificity of 58.1%, an AUC of 0.640, and 95% CI=0.554-0.769. Conclusion:Mel-frequency cepstral coefficients, formant frequencies, intensity features, and energy features may have specific changes in female patients with anhedonic depression.The Mel-frequency cepstral coefficients has the highest recognition accuracy for anhedonic symptoms in female depression patients, and is expected to become an objective evaluation index for female anhedonic depression.

Objective:To analyze the influencing factors for depression in primary school children aged 9-10 years in Jiangsu Province, and to construct a risk prediction model.Methods:A retrospective study.A total of 1 162 primary school children aged 9-10 years from 3 primary schools in 3 regions of Jiangsu Province were recruited.Their demographic data were collected, and they were surveyed by the Depression Anxiety Stress Scales-21 (DASS-21), the Strengths and Difficulties Questionnaire (SDQ), and the Family Environment Scale (FES). Children were divided into control group (1 059 cases) and depression group (103 cases) based on the depression scores obtained from the DASS-21 scale.Multivariate Logistic regression analysis was used to analyze the influencing factors for depression in primary school students aged 9-10 and construct a risk prediction model. Results:There were significant differences in the economic development region, physical activities, academic performance, student cadres, parents′ education level, frequency of parental quarrels, SDQ and FES dimension scores between control group and depression group (all P<0.05). Among them, economic development areas (Northern Jiangsu and Southern Jiangsu), student cadres, father′s education level (elementary school and below) and intimacy of the FES scale were protective factors for depression in elementary school children; while emotional symptoms, peer problems and the total difficulty score in the SDQ scale, and the conflict in the FES scale were the risk factors for depression in elementary school children.The prediction model was created based on the influencing factors: Logit ( P)=-1.390×economic development area (Northern Jiangsu) -1.508×economic development area (Southern Jiangsu) -1.248×student cadres -2.206×father′s education level (primary school and below) -1.145×father′s education level (junior high school)+ 3.316×emotional symptoms in the SDQ+ 0.979×peer problems in the SDQ+ 2.520×total difficulty score in the SDQ -1.697×cohesion in the FES + 0.760×conflict in the FES -0.678.The area under the curve of receiver operating characteristic was 0.931, with the sensitivity and specificity of 85.42% and 91.83%, respectively. Conclusions:The regional level of economic development, class or school cadres, father′s education level, peer problems, total difficulty score, cohesion and conflict in the family are influencing factors for depression among primary school children aged 9-10 years in Jiangsu Province.The created prediction model can effectively assess the depressive risk factors in this population, which is conductive to achieve the early recognition and intervention of depression in them.

BACKGROUND: Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. METHODS: This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. RESULTS: After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. CONCLUSIONS Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.
Adult ; Humans ; United States/epidemiology* ; Nitrates/adverse effects* ; Nutrition Surveys ; Thiocyanates/urine* ; Perchlorates/urine* ; Creatinine ; Environmental Exposure ; Renal Insufficiency, Chronic/epidemiology* ; Logistic Models

Objective: To investigate craniofacial differences in individuals with hypodontia and explore the relationship between craniofacial features and the number of congenitally missing teeth. Methods: A cross-sectional study was conducted among 261 Chinese patients (males, 124; females, 137; age, 7–24 years), divided into four groups (without hypodontia: no teeth missing, mild: one or two missing teeth, moderate: three to five missing teeth, severe: six or more missing teeth) according to the number of congenitally missing teeth. Differences in cephalometric measurements among the groups were analyzed. Further, multivariate linear regression and smooth curve fitting were performed to evaluate the relationship between the number of congenitally missing teeth and the cephalometric measurements. Results: In patients with hypodontia, SNA, NA-AP, FH-NA, ANB, Wits, ANS-Me/N-Me, GoGn-SN, UL-EP, and LL-EP significantly decreased, while Pog-NB, AB-NP, N-ANS, and S-Go/N-Me significantly increased. In multivariate linear regression analysis, SNB, Pog-NB, and S-Go/N-Me were positively related to the number of congenitally missing teeth. In contrast, NA-AP, FH-NA, ANB, Wits, N-Me, ANS-Me, ANS-Me/N-Me, GoGn-SN, SGn-FH (Y-axis), UL-EP, and LL-EP were negatively related, with absolute values of regression coefficients ranging from 0.147 to 0.357. Further, NA-AP, Pog-NB, S-Go/N-Me, and GoGn-SN showed the same tendency in both sexes, whereas UL-EP and LL-EP were different. Conclusions Compared with controls, patients with hypodontia tend toward a Class III skeletal relationship, reduced lower anterior face height, flatter mandibular plane, and more retrusive lips. The number of congenitally missing teeth had a greater effect on certain characteristics of craniofacial morphology in males than in females.

Objective: To analyze the correlation between third molar agenesis and craniofacial morphology by studying the location and number of congenital missing third molars and results of craniofacial cephalometric measurement. Methods: A total of 123 patients were included, including 64 patients in the control group without congenital third molar absence and 59 patients in the absence group with at least one third molar absent. Cephalometric measurements included FMA, IMPA, AR-Go, GoGn-Sn, Co-A, Co-Gn, ANS-Me, Go-Me, SN-MP, Ar-Go-Me, SNA, SNB, ANB, Y-axis angle, Y-axis length, Ar-Go, Go-Me, MP-OP, FH-PP, FH-OP, a total of 18 bone tissue indicators, U1-SN, U1-L1, U1-NA, L1-NB, U1-APo and L1-APo, a total of 6 dental indicators, and UL-EP, LL-EP and nasolabial angle, a total of 3 soft tissue indicators. The correlation between congenital agenesis of third molars and craniofacial morphology was analyzed. Results: The most common missing location of the third molar occured in the upper jaw and the most common number of missing teeth was one. In control group, Ar-Go-Me and SN-MP were larger (P<0.05), U1-SN, U1-NA, L1-NB, UL-EP and LL-EP were larger (P<0.05), and U1-L1 was smaller (P<0.01). There were no significant differences in Ar-Go and Go-Me between the two groups(P>0.05). Conclusion Patients with four third molars are more likely to have backward and downward rotation of the mandible and are more likely to develop into a convex facial type than patients with missing third molars, which has a higher correlation with hyperdivergent growth pattern and convex facial type.