OBJECTIVES: To investigate the therapeutic mechanism of nodakenin for Crohn's disease (CD)-like colitis in mice. METHODS: Using a colonic organoid model with lipopolysaccharide (LPS)- and ATP-induced pyroptosis, we investigated the effects of nodakenin on pyroptosis, intestinal barrier function and inflammatory response by detecting key pyroptosis-regulating factors and assessing changes in permeability and pro-inflammatory factors. In a mouse model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced CD-like colitis, the therapeutic effect of nodakenin was evaluated by measuring changes in body weight, DAI score, colonic histopathologies, inflammation score, intestinal barrier function and intestinal epithelial cell pyroptosis. The mechanism of nodakenin protection against pyroptosis of intestinal epithelial cells was explored using network pharmacology analysis and in vivo and in vitro experiments. RESULTS: In LPS- and ATP-induced colonic organoids, treatment with nodakenin significantly inhibited the expressions of NLRP3, GSDMD-N, cleaved caspase-1 and caspase-11, improved intestinal FITC-dextran (FD4, 4000) permeability, and decreased the levels of IL-1β and IL-18. In the mouse model of TNBS-induced colitis, nodakenin treatment significantly alleviated weight loss, reduced DAI score, inflammatory cell infiltration and inflammation score, and decreased serum FD4 and I-FABP levels and bacteria translocation to the mesenteric lymph nodes, spleen and liver. The mice with nodakenin treatment had also lowered expressions of NLRP3, GSDMD-N, cleaved caspase-1 and caspase-11 in the intestinal mucosa. Network pharmacology analysis suggested that the inhibitory effect of nodakenin on colitis was associated with the PI3K/Akt pathway. In both the colonic organoid model and mouse models of colitis, nodakenin effectively inhibited the activation of the PI3K/Akt pathway, and the application of IGF-1, a PI3K/Akt pathway activator, strongly attenuated the protective effect of nodakenin against intestinal epithelial cell pyroptosis and intestinal barrier dysfunction. CONCLUSIONS Nodakenin protects intestinal barrier function and alleviates CD-like colitis in mice at least partly by inhibiting PI3K/Akt signaling to reduce intestinal epithelial cell pyroptosis.
Animals ; Pyroptosis/drug effects* ; Mice ; Trinitrobenzenesulfonic Acid ; Colitis/drug therapy* ; Epithelial Cells/drug effects* ; Intestinal Mucosa/cytology* ; Disease Models, Animal ; Coumarins/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Crohn Disease/drug therapy*

Musculoskeletal disorders (MSDs) are characterized by extensive pathological involvement and high prevalence and cause a significant disease burden. Long-term drug administration often causes by adverse effects with poor therapeutic efficacy. Low-intensity pulsed ultrasound (LIPUS), as a specialized therapeutic modality, delivers acoustic energy at a low intensity in a pulsed wave mode, thus ensuring stable energy transmission to the target tissues while minimizing thermal effects. This non-invasive approach has demonstrated significant potential for MSD treatment by delivering effective physical stimulations. Extensive animal and clinical studies have demonstrated the efficacy of LIPUS for accelerating the healing process of fresh fractures and nonunions, promoting soft tissue regeneration and suppressing inflammatory responses. Emerging evidence suggests promising applications of LIPUS in skeletal muscle injury treatment and promoting tissue regeneration and repair. This review outlines the recent advancements and mechanistic studies of LIPUS for treatment of common MSDs including fractures, nonunions, muscle injuries, and osteoarthritis, addressing also the technical parameters of commercially available LIPUS devices, current therapeutic approaches, the existing challenges, and future research directions.
Humans ; Ultrasonic Therapy/methods* ; Musculoskeletal Diseases/therapy* ; Ultrasonic Waves ; Osteoarthritis/therapy* ; Muscle, Skeletal/injuries*

OBJECTIVES: This study aimed to evaluate the filling effects of three biomaterial root canal sealers [iRoot SP, C-Root SP, and GuttaFlow Bioseal (GFB)] by using Micro-CT. METHODS: Sixty single-canal detached premolars were selected. After crown amputation, their uniform working length was set at 12 mm and prepared to a 06 taper 30# with M3 nickel-titanium file. The samples were randomly divided into six groups with different sealers and obturation techniques: iRoot SP+single-cone technique (SC), C-Root SP+SC, GFB+SC, iRoot SP+single cone-mediated ultrasonic technique (SU), C-Root SP+SU, and GFB+SU. Samples were scanned by Micro-CT, and the total and segmented filling rates were calculated with Mimics 22.0 software after 3D reconstruction. RESULTS: The overall filling rate of the three biomaterial root canal sealers was higher than 90%. The overall and coronal third and middle third segment filling rate of groups iRoot SP+SC, C-Root SP+SC was higher than that of group GFB+SC (P<0.01), with no significant difference between groups iRoot SP+SC and C-Root SP+SC (P>0.05). On the apical third, no significant difference was found among each group (P>0.05). The overall and segment filling rate of groups iRoot SP+SU and C-Root SP+SU was higher than that of GFB+SU (P<0.01), with no significant difference between groups iRoot SP+SU and C-Root SP+SU (P>0.05). The filling rate of the apical 1/3 of group C-Root+SC was lower than that of group C-Root+SU (P<0.01), and the filling rate of the coronal 1/3 of group GFB+SC was higher than that in the GFB+SU (P<0.01). Nevertheless, no significant difference was found in other filling rate of two obturation techniques (P>0.05). CONCLUSIONS The overall filling rate of the three biomaterial root canal sealers using SC and SU are satisfactory. iRoot SP and C-Root SP have similar filling rates, which are significantly higher than that of GFB. C-Root SP combined with SU technique can improve the filling quality of the root apical.
Root Canal Filling Materials ; X-Ray Microtomography ; Humans ; Root Canal Obturation/methods* ; Gutta-Percha ; Dimethylpolysiloxanes ; Drug Combinations ; Dental Pulp Cavity/diagnostic imaging* ; Bicuspid

Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

Objective:To explore the correlation between the elevation of glycated hemoglobin A1c (HbA1c) in the first trimester and its change from the first to the second trimester and adverse pregnancy outcomes.Methods:This was a bidirectional cohort study. Singleton pregnant women who delivered in the First Affiliated Hospital, Sun Yat-sen University from March 1, 2021, to July 31, 2024, and had HbA1c results in the first and second trimesters were included. Those with HbA1c<5.7% in the first trimester were described as group E1, and those with HbA1c between 5.7% and 6.4% were described as group E2. Those with HbA1c<5.2% in the second trimester were described as group S1, and those with HbA1c between 5.2% and 6.4% were described as group S2. Accordingly, the changing trend of HbA1c from the first to the second trimester was divided into group E1-S1, group E1-S2, group E2-S1, and group E2-S2. Clinical indicators such as gestational diabetes mellitus (GDM), preeclampsia, preterm birth, preterm premature rupture of membranes (PPROM), polyhydramnios, large for gestational age infants, small for gestational age infants, neonatal hypoglycemia, and neonatal transfer were collected. Comparisons between groups were performed using t-tests, analysis of variance, Mann-Whitney U tests, Kruskal-Wallis tests, Chi square tests, and Fisher's exact test. Multivariate logistic regression analysis was used to analyze the impact of HbA1c in the first trimester and the changing trend of HbA1c from the first to the second trimester on pregnancy outcomes. Results:During the study period, a total of 6 500 pregnant women were included for analysis, among which 209 (3.2%) had HbA1c between 5.7% and 6.4% in the first trimester. Taking those with HbA1c<5.7% as a reference, HbA1c between 5.7% and 6.4% in the first trimester was an independent risk factor for GDM, preterm birth, and PPROM [ OR (95% CI) were 3.304 (2.465-4.427), 1.545 (1.008-2.368), and 1.872 (1.042-3.361), respectively]. Taking group E1-S1 as a reference, HbA1c<5.7% in the first trimester and 5.2%-6.4% in the second trimester (group E1-S2) was an independent risk factor for GDM, preterm birth, PPROM, and neonatal hypoglycemia [ OR (95% CI) were 2.770 (2.370-3.237), 1.424 (1.132-1.791), 1.614 (1.179-2.211), and 2.047 (1.024-4.092), respectively]; HbA1c between 5.7% and 6.4% in the first trimester and<5.2% in the second trimester (group E2-S1) was an independent risk factor for PPROM [ OR (95% CI) was 3.408 (1.187-9.784)]; HbA1c between 5.7% and 6.4% in the first trimester and 5.2%-6.4% in the second trimester (group E2-S2) was an independent risk factor for GDM and preterm birth [ OR (95% CI) were 4.651 (3.282-6.592) and 1.724 (1.066-2.786), respectively]. Conclusions:HbA1c between 5.7% and 6.4% in the first trimester was significantly associated with an increased risk of GDM, preterm birth, and PPROM. For those with HbA1c between 5.7% and 6.4% in the first trimester, if the HbA1c level decreased in the second trimester, only the risk of PPROM increased significantly; conversely, if the HbA1c level continued to increase in the second trimester, the risks of GDM and preterm birth both increased significantly.

Objective:To investigate the risk of falls in patients with Parkinson's disease and establish and validate a prediction model.Methods:We selected 372 patients with Parkinson's disease at Sichuan Nanchong Mental Health Centre from January 2022 to Septem-ber 2023.The patients were divided in a 7:3 ratio into model group(260 cases)and validation group(112 cases).According to previ-ous literature and suspected factors found in clinical practice,we collected general information(sex,age,etc.)and disease-related factors(the duration of Parkinson's disease,the type of medications taken,etc.)that may be associated with falls in patients with Parkinson's disease.In the model group,between patients with and those without falls within 1 year as reported by the patients or their family members,potential predictors for falls were determined through comparison of general information and disease-related factors,least absolute shrinkage and selection operator(LASSO)regression,and multivariable logistic regression.Based on the significant factors,a nomogram model was established and validated.Results:In the model group,81(31.15%)of the 260 patients experienced falls.According to the LASSO regression and multivariable logistic regression results,alcohol consumption,the type of medications,the score of the Unified Parkinson's Disease Rating Scale part Ⅲ(UPDRS-Ⅲ),the Berg Balance Scale score,the presence of arthritis,and the presence of osteoporosis were independent factors influenc-ing falls in patients with Parkinson's disease.The area under curve(AUC)of the receiver operator characteristic curve(ROC)for pre-dicting the risk of falls in patients with Parkinson's disease was 0.896(95%CI=0.856-0.935)in the model group and 0.883(95%CI=0.840-0.926)in the validation group.The calibration curve analysis results showed that the prediction curves of the model and valida-tion groups closely fitted the standard curves.The decision curve analysis results indicated that when the probability threshold for pre-dicting the fall risk in Parkinson's disease using the nomogram was 0.10-0.90,the net benefit rate of the patients was greater than 0.Conclusion:The risk of falls in patients with Parkinson's disease are mainly influenced by factors such as alcohol consumption and the type of medications.The nomogram model established in this study can be used to predict the fall risk in patients with Parkinson's disease.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

BACKGROUND:The use of exosomes as drug carriers can not only precisely target the therapeutic site,but also increase the local concentration,opening up a new way for drugs to enter the central nervous system.OBJECTIVE:To explore the biogenesis and biological functions of exosomes and summarize the current state-of-the-art regarding extracellular vesicles as drug carriers in the treatment of central nervous system diseases.METHODS:The first author searched Web of Science,PubMed,and CNKI for relevant literature from January 1976 to January 2024.The English search terms were"exosomes,extracellular vesicles,central nervous system,drug delivery,ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."The Chinese search terms were"exosomes,extracellular vesicles,central nervous system diseases,drug delivery,stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,brain tumor."Finally,94 articles were included for analysis.RESULTS AND CONCLUSION:(1)Exosomes can easily cross the blood-brain barrier and deliver proteins,metabolites,and nucleic acids to recipient cells to regulate cellular metabolism.Since exosomes are small vesicles secreted by cells,they have a much lower circulating immunogenicity and can be less likely to be recognized and cleared by macrophages in the internal circulation.(2)Exosomes can be engineered to deliver different therapeutically ingredients,including RNA,proteins,chemotherapeutic drugs,and immunomodulators,and are capable of delivering them to the desired target areas.Engineered modified exosomes have better targeting properties.Furthermore,this exosome-mediated delivery is extremely low in immunogenicity and is expected to provide a safer and more effective method for precision therapy of central nervous system diseases in the future.

Objective This study aims to investigate controversial cases of forensic clinical re-identification of fractures,exploring the characteristics,causes,and countermeasures related to identification errors in primary bone injuries,complications,and subsequent changes.The goal is to provide identification strategies for similar cases regarding the collection of identification materials,timing,and examination method selection,ultimately establishing a paradigm for such identifications.Methods A total of 103 cases of clinical re-identification of fractures accepted by the West China Forensic Identification Center from 2020 to 2024 were collected,and the data from initial identifications and re-identifications were retrospectively analyzed.Results Male cases accounted for 69.90%of the re-identifications,with disability grade(67.96%)and injury degree(30.10%)being the primary concerns.Individual requests represented a high proportion(92.86%)in the initial assessment of disability levels,while unit or joint requests dominated the re-assessment(92.86%).The agreement rates for disability grade and injury degree were 55.26%and 59.38%,respectively.The reassessment of disability grades primarily involved fractures of limb long bones,spine,and ribs,with 75.53%of opinions resulting in downgraded disability levels.Rib,orbital,and nasal bone fractures were the main focus in injury degree reassessments,with 84.62%of opinions indicating aggravated injuries.The consistency rates for fracture identification in disability grade assessments was 92.21%,while rates for injury degree and sequelae were 65.63%and 48.94%,respectively.Inconsistencies in identifying damage facts—including the presence of fractures,distinguishing between fresh and old fractures,and determining the nature of fractures and sequelae—were primarily noted in rib,orbital,and nasal bone fractures.The utilization rate of CT metadata in initial evaluations(25.00%)was significantly lower than in re-evaluations(95.00%).The identification time for joint mobility dysfunction after fracture in re-identifications was significantly longer than in initial identifications(P=0.0002),and the identification time for cases with agreement was significantly shorter than for cases with disagreement(P=0.036).Conclusion Image data type and identification timing are critical factors that may influence the accuracy and consistency of forensic clinical identification of bone injuries.When necessary,dynamic CT metadata in conjunction with image post-processing technology can be routinely employed to identify fractures of the ribs,orbital bones,or nasal bones,thereby reducing the risk of misidentification.