Purpose: This study evaluated the performance of the YOLOv8m-seg model in detecting and delineating interproximal caries and cervical burnout on bitewing radiographs and examined whether increasing the number of training epochs improved segmentation accuracy and consistency. Materials and Methods: In total, 1,410 bitewing radiographs were annotated using polygon-based masks by a trained dental clinician. The YOLOv8m-seg model was trained for 50, 100, and 150 epochs on 1,128 images and validated on 282 images using the Ultralytics segmentation framework. Model performance was assessed using precision, recall, and mean average precision at intersection-over-union thresholds of 0.5 and 0.5 to 0.95 (mAP0.5, mAP0.5-0.95) for both bounding box and mask outputs. Additional evaluation was conducted on a non-augmented validation subset. Results: Extended training duration was associated with improved segmentation performance. The highest mask mAP0.5-0.95 value was 0.828 at epoch 150. Both box-based precision and recall increased with longer training, whereas mask-based evaluation more accurately reflected the model’s ability to delineate the boundaries of caries and cervical burnout. Performance appeared consistent across both classes in the augmented validation split but was reduced in the non-augmented validation subset. Conclusion The YOLOv8m-seg model demonstrated high diagnostic accuracy in distinguishing proximal caries from cervical burnout on bitewing radiographs. Its mask-based outputs may assist clinicians in early lesion recognition and support improved diagnostic decision-making. Future studies should evaluate model generalizability across broader populations and diverse clinical environments and should prioritize assessment using non-augmented validation sets and independent test datasets.

Introduction: The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management has inadvertently perpetuated demand for unregulated experimental peptides procured through gray markets. Retatrutide, a novel triple GLP-1/glucose-dependent insulinotropic polypeptide (GIP)/glucagon receptor agonist undergoing Phase III trials; AOD -9604, an abandoned synthetic human growth hormone fragment; and tesamorelin, a synthetic GHRH analogue, are increasingly self-administered without medical supervision. Their combined metabolic and thromboembolic risks remain unknown and unreported. Case: A 50-year-old Malaysian female with morbid obesity and poorly controlled type 2 diabetes mellitus (hemoglobin A1c 13%) presented with acute dyspnea, chest tightness, syncope, and cardiogenic shock. Three weeks prior, she had self-initiated subcutaneous retatrutide, AOD-9604, and tesamorelin procured through unregulated online platforms, achieving rapid weight loss of 10 kg. Despite markedly reduced oral intake from GLP-1-mediated gastrointestinal side effects, she continued her prescribed high-dose insulin regimen and sodium-glucose cotransporter-2 (SGLT2) inhibitor without dose adjustment. She developed concurrent diabetic ketoacidosis, confirmed biochemically, alongside massive saddle pulmonary embolism with right ventricular strain on echocardiography and computed tomography pulmonary angiography. She was successfully treated with systemic thrombolysis using alteplase, guideline-directed diabetic ketoacidosis management including fixed-rate insulin infusion and fluid resuscitation, and anticoagulation. The SGLT2 inhibitor was withheld throughout admission. She was discharged on rivaroxaban with counseling to cease all unregulated compounds. All three agents were submitted to the National Pharmaceutical Regulatory Authority/Malaysian Adverse Drug Reactions Advisory Committee for adverse drug reaction reporting. Conclusion To our knowledge, this is the first reported case of concurrent massive pulmonary embolism and diabetic ketoacidosis precipitated by unsupervised gray-market retatrutide, AOD-9604, and tesamorelin. Clinicians should enquire about unregistered supplement use, counsel insulin-dependent patients on sick-day rules when appetitesuppressing agents are initiated, and report adverse events to pharmacovigilance authorities.
AOD 9604 ; tesamorelin ; Diabetic Ketoacidosis ; Pulmonary Embolism ; Peptides

Objective To compare the positioning errors and the motion of acromioclavicular joint in breast cancer patients with integrated cervicothoracic thermoplastic membrane and breast bracket fixation,and to provide reference for accurate irradiation of upper and lower clavicular region.Methods Sixty-three pa-tients with breast cancer who were treated in the radiotherapy center of the hospital from November 1,2021 to August 9,2023 were selected as the study objects,and were divided into the integrated cervicothoracic thermo-plastic membrane group(n=32)and breast bracket group(n=31)according to different positioning meth-ods.The translation errors of left and right direction(X),head and foot direction(Y)and ventral and dorsal direction(Z)and the rotation errors of sagittal plane(Rx),cross section(Ry)and coronal plane(Rz)of the two groups were analyzed,and the movement amplitude and three-dimensional displacement of acromioclavic-ular joint were measured respectively.Results Compared with the breast bracket group,X translation errors[(0.18±0.14)cm vs.(0.15±0.12)cm]and Z translation errors[(0.19±0.14)cm vs.(0.16±0.14)cm]of the cervicothoracic thermoplastic memberane group were greater,Z translation error[(0.21±0.17)cm vs.(0.22±0.21)cm]and Rx rotation error of cervical and sternoclavicular joints[(0.93±0.87)° vs.(1.08±0.92)°]were smaller,Rz rotation error[(1.00±0.94)° vs.(0.95±0.86)°]was greater,and the motion ΔX of acromioclavicular joint[(0.18±0.15)cm vs.(0.25±0.21)cm]was smaller,the difference was statistically significant(P＜0.05).Conclusion Integrated cervicothoracic thermoplastic membrane can be used as a solu-tion for prophylactic irradiation of breast cancer in the upper and lower clavicular region and for radiation leak-age in the presence of metastasis.

Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Objective:To explore the relationship between anxiety status and progestogen level in perimenopausal women and their effects on the pathogenesis of uterine fibroid.Methods:A total of 376 perimenopausal women who visited the Department of Gynecology and Neurology of Nanjing Tongren Hospital affiliated School of Medicine of Southeast University from August 2019 to July 2023 were selected as the study subjects.Based on the and divided into two groups according to the Self-Rating Anxiety Scale(SAS),they were divided into a non-anxiety group(n=202,SAS score<50)and an anxiety group(n=174,SAS score≥50).Additionally,according to the presence or absence of uterine fibroids,they were categorized into a non-uterine fibroid group(n=225)and a uterine fibroid group(n=151).The t test or x2 test was used to compare general demographic and clinical data between the non-uterine fibroid group and the uterine fibroid group.Multivariate logistic regression analysis was used to analyze the correlation between anxiety status,progesterone level,and uterine fibroid risk in perimenopausal women.The bootstrap method was used to analyze whether progesterone level mediate the relationship between anxiety status and uterine fibroid risk.Results:Comparison of baseline data between the non-uterine fibroid group and the uterine fibroid group showed that previous caesarean section,number of abortions,hemoglobin level,neutrophil count,lymphocyte count,and neutrophil-to-lymphocyte ratio(NLR)were not associated with the incidence of uterine fibroid(all P>0.05).In contrast,menstrual period,menstrual cycle,progesterone level,and SAS score were significantly associated with the incidence of uterine fibroid(all P<0.05).Analysis of the effects of different clinical features on the risk of uterine fibroid showed that age,chronic diseases history,and dysmenorrhea history were all significantly associated with the incidence of uterine fibroid in perimenopausal women(all P<0.05).Further,univariate logistic regression analysis showed that age≥55 years,chronic diseases,and dysmenorrhea were significant risk factors for uterine fibroid in perimenopausal women(all P<0.05).These seven significant risk factors(menstrual period,menstrual cycle,progesterone level,SAS score,age,chronic disease history,and dysmenorrhea history)were included in a multivariate logistic regression analysis,which identified SAS score and progesterone level as independent risk factors for uterine fibroid in perimenopausal women.Specifically,SAS score was positively correlated with uterine fibroid risk,while progesterone level was negatively correlated with the risk.Restriction cubic spline analysis showed a nonlinear quantitative response relationship between continuously changing progesterone level and the risk of uterine fibroid(x2=12.315,P<0.001),when progesterone level was≤2.00 ng/mL,the risk of uterine fibroid decreased with the increase of progesterone level(HR=1.014,95%CI:1.006-1.012,P<0.001),and when progesterone level was>2.00 ng/mL,the risk of uterine fibroid stabilized with further increases in progesterone level(HR=1.003,95%CI:0.998-1.002,P=0.001).After further adjusting for a variety of related confounding factors affecting the incidence of uterine fibroid in perimenopausal women,it was found that SAS score was an independent risk factor for predicting the incidence of uterine fibroid in perimenopausal women.Mediation effect analysis revealed that SAS score had a direct effect on the incidence of uterine fibroid(β1=0.202,95%CI:0.124-0.216),and progesterone level partially mediated the effect of SAS score on uterine fibroid risk(β2=0.196,95%CI:0.152-0.207).The total effect value was βtotal=0.398,and the mediating effect accounted for 49.25%of the total effect.Conclusion:There was an independent correlation between anxiety status and progestogen level in perimenopausal women,anxiety status was a risk factor for the development of uterine fibroids,while progestogen levelwas a protective factor.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases