OBJECTIVE: To develop a clinical automated diagnostic system for temporomandibular disorders (TMD) based on the diagnostic criteria for TMD (DC/TMD) to assist dentists in making rapid and accurate clinical diagnosis of TMD. METHODS: Clinical and imaging data of 354 patients, who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024, were retrospectively collected. The study developed a clinical automated diagnostic system for TMD using the DC/TMD, built on the. NET Framework platform with branching statements as its internal structure. Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored. Diagnostic efficacy of the TMD clinical automated diagnostic system for degenerative joint diseases, disc displacement with reduction, disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evaluated and compared with a specialist in the field of TMD. Accuracy, precision, specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist. RESULTS: Diagnoses for various TMD subtypes, including pain-related TMD (arthralgia, myalgia, headache attributed to TMD) and intra-articular TMD (disc displacement with reduction, disc displacement with reduction with intermittent locking, disc displacement without reduction with limited opening, disc displacement without reduction without limited opening, degenerative joint disease and subluxation), using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD specialist based on DC/TMD. Both the system and the expert showed low sensitivity for diagnosing degenerative joint disease (0.24 and 0.37, respectively), but high specificity (0.96). Both methods achieved high accuracy (> 0.9) for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening. The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system, lower than the expert (0.87), while both had high specificity (0.92). The Kappa values for most TMD subtypes were close to 1, except the disc displacement without reduction without limited mouth opening, which had a Kappa value of 0.68. CONCLUSION This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD. The system is designed to facilitate the rapid and accurate diagnosis and classification of TMD, and is expected to be an important tool in clinical scenarios.
Humans ; Temporomandibular Joint Disorders/diagnosis* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Facial Pain/diagnosis* ; Diagnosis, Computer-Assisted/methods* ; Sensitivity and Specificity ; Young Adult

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.
Humans ; Lysosomes/physiology* ; Autophagy/physiology* ; Nanomedicine/methods* ; Neurodegenerative Diseases/therapy* ; Animals ; Nanostructures ; Lysosomal Storage Diseases/therapy*

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

The high content of sucrose and raffinose reduces the prebiotic value of soybean oligosaccharides. Fructan sucrases can catalyze the conversion of sucrose and raffinose to high-value products such as fructooligosaccharides and melibiose. To obtain a fructan sucrase that can efficiently convert soybean oligosaccharides, we first mined the fructan sucrase gene from microorganisms in the coastal areas of Xisha Islands and Bohai Bay and then characterized the enzymatic and catalytic properties of the enzyme. Finally, recombinant extracellular expression of this gene was carried out in Bacillus subtilis. The results showed that a novel fructan sucrase, BhLS 39, was mined from Bacillus halotolerans. With sucrose and raffinose as substrates, BhLS 39 showed the optimal temperatures of 50 ℃ and 55 ℃, optimal pH 5.5 for both, and K_cat/K_m ratio of 3.4 and 6.6 L/(mmol·s), respectively. When 400 g/L raffinose was used as the substrate, the melibiose conversion rate was 84.6% after 30 min treatment with 5 U BhLS 39. Furthermore, BhLS 39 catalyzed the conversion of sucrose to produce levan-type-fructooligosaccharide and levan. Then, the recombinant extracellular expression of BhLS 39 in B. subtilis was achieved. The co-expression of the intracellular chaperone DnaK and the extracellular chaperone PrsA increased the extracellular activity of the recombinant BhLS 39 by 5.2 folds to 17 U/mL compared with that of the control strain. BhLS 39 obtained in this study is conducive to improving the quality and economic benefits of soybean oligosaccharides. At the same time, the strategy used here to enhance the extracellular expression of BhLS 39 will also promote the efficient recombinant expression of other proteins in B. subtilis.
Oligosaccharides/metabolism* ; Glycine max/metabolism* ; Bacillus subtilis/metabolism* ; Sucrase/biosynthesis* ; Raffinose/metabolism* ; Fructans/metabolism* ; Sucrose/metabolism* ; Bacillus/genetics* ; Recombinant Proteins/biosynthesis* ; Bacterial Proteins/biosynthesis*

Objective To investigate the levels of vascular endothelial growth factor(VEGF)and vas-cular endothelial growth factor receptor 2(VEGFR2)in serum and urine of the children patients with primary nephrotic syndrome(PNS),and to conduct the correlation analysis on the experimental indexes of 24 h urine protein quantitation,blood albumin(ALB),total cholesterol(TC),blood urea nitrogen(BUN)and creatinine(Scr).Methods Thirty children patients with PNS without hormone treatment admitted and treated in this hospital from January 2020 to December 2023 were selected as the study subjects and divided into the hormone sensitive nephrotic syndrome(SSNS)group(n=12)and steroid dependent nephrotic syndrome(SDNS)group(n=18)according to the cortical hormone treatment effect.Twenty healthy children with matched age and sex visiting in the pediatric department during the same period served as the control group.The differ-ences of VEGF and VEGFR2 levels in blood and urine were compared among 3 groups and their correlation with the experimental indexes was analyzed.Results Compared with the control group,the blood VEGF lev-el,urine VEGF and BUN levels in the SDNS group were increased,blood VEGFR2 and urine VEGFR2,24 h urine protein quantitation and TC level in the SSNS group and SDNS group were increased,the ALB level was decreased,and the differences were statistically significant(P<0.05).The Pearson correlation analysis re-sults showed that blood VEGF level was positively correlated with the 24 h urine protein quantitation and TC level,and negatively correlated with the ALB level(P<0.05);the urine VEGF level was positively correlated with 24 urine protein quantitation and TC level,and negatively correlated with the Scr level(P<0.05);blood VEGF2 level was positively correlated with the 24 h urine protein quantitation and the TC level,and negative-ly correlated with the ALB level(P<0.05);the urine VEGF2 level was positively correlated with the 24 h u-rine protein quantitation and TC level,and negatively correlated with the ALB level(P<0.05).Conclusion The blood and urine VEGF and VEGFR2 may serve as the novel indicators for the early diagnosis,prediction and hormone sensitivity evaluation in the children patients with PNS.

Temporal lobe epilepsy(TLE)is the most common form of focal epilepsy in adults,characterized by spontaneous recurrent seizures,with most patients experiencing drug resistance and cognitive dysfunction.MicroRNAs(miRNAs)play a critical role in the pathological process of TLE through their regulation of post-transcriptional gene expression.The pathogenesis of TLE has not been fully elucidated,lacking effective clinical therapeutic targets and prognostic markers.This review sum-marized the expression changes of miRNAs in TLE and their research progress as potential biomarkers,aiming to provide new insights into the early diagnosis,prognosis evaluation,and pathogenic mecha-nisms of TLE.

Objective To investigate the relationship between left ventricular hypertrophy(LVH)diagnosed by Peguero-Lo-Presti index and recurrence of paroxysmal atrial fibrillation(AF)after radiofrequency ablation.Methods A total of 652 patients with paroxysmal atrial fibrillation who underwent radiofrequency ablation were selected.According to Peguero-Lo-Presti index,patients were divided into the LVH group(167 cases)and the normal left ventricle group(485 cases).Baseline data were collected,and regular follow-up was performed at 3,6 and 12 months after radiofrequency catheter ablation.The recurrence of AF was assessed.Kaplan-Meier survival curve was used to analyze the recurrence rate of AF in the two groups.Cox proportional hazard model was used to assess risk factors for recurrent atrial fibrillation.Results The median follow-up time was 20.5(15.0,26.0)months.A total of 155 patients(23.8%)developed recurrence of AF,including 95 patients in the LVH group and 60 patients in the LVN group.The recurrence rate without AF was significantly lower in the LVH group than that in the LVN group(64.1%vs.80.4%,Log-rank χ2=26.361,P＜0.01).After adjusting for age,sex,body mass index,hypertension,diabetes,coronary heart disease,cardiac dysfunction,left anteroposterior and posterior atrial diameter,left ventricular end-diastolic diameter,and left ventricular ejection fraction,LVH diagnosed by Peguero-Lo-Presti index was still a risk factor for recurrent AF[HR(95%CI):2.359(1.663-3.345),P＜0.01].Conclusion In patients with paroxysmal AF,LVH diagnosed by Peguero-Lo-Presti index is a risk factor of AF recurrence after radiofrequency catheter ablation.

Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.