OBJECTIVE: To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset. METHODS: By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset. RESULTS: An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038). CONCLUSION Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans ; Phenotype ; Biological Ontologies ; Language ; Software ; Large Language Models

OBJECTIVE: The aim of this study is to investigate the risk factors of prognosis in patients with early-onset prostate cancer treated without surgery. A nomogram will be constructed and validated to predict overall survival (OS) of patients with early-onset prostate cancer treated without surgery. METHODS: The clinical data was obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database on prostate cancer patients aged 18－55 years who were treated without surgery between 2010 and 2015. The clinical data set was divided into training set and validation set according to 7∶3 ratio, including age, race, marital status, Gleason score, prostate specific antigen (PSA) and other 8 factors. And significant variables were screened by univariate Cox regression analysis. Multivariate Cox regression analysis was used to identify the influence factors. Stepwise regression method was used to select the most influential factors on the total OS, and R software was used to build a nomogram model. The accuracy and prediction ability of the model were verified by drawing receiver operating characteristic (ROC) and Calibration Plot. The clinical benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: A total of 8 212 patients who met the criteria were randomly assigned to the training set (n=5 752) or validation set (n=2 460), with no statistical difference between the two groups (all P>0.05). Six factors were identified through univariate and multivariate Cox regression analysis including marital status, N stage, M stage, radiotherapy, PSA and Gleason score, which were most closely associated with the OS of prostate cancer patients, and a column graph model was constructed based on these factors. The Consistency index (C-index) of the model in the training set and the verification set were 0.802 and 0.794, respectively. And the apparent diffusion coefficient (AUC) was 0.851, 0.855 and 0.855 for training sets 1, 3 and 5 years, and 0.694, 0.860 and 0.832 for verification sets 1, 3 and 5 years. The calibration chart showed a good agreement between the predicted and actual values of the model. In the analysis of decision curve, the model showed good clinical application value. CONCLUSION The prediction model based on marital status, radiotherapy, M stage, N stage, PSA and Gleason score for early-onset prostate cancer patients without surgical treatment has certain reference value which is expected to become an effective tool for clinicians to treat in future prospective studies on large and multi-center samples.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Middle Aged ; Nomograms ; SEER Program ; Prognosis ; Adult ; Prostate-Specific Antigen ; Risk Factors ; Proportional Hazards Models ; Neoplasm Grading ; ROC Curve

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

BACKGROUND: As research progresses, there is a growing body of evidence indicating that urinary metallothionein (MT) levels may be elevated in individuals exposed to cadmium (Cd). This study aimed to investigate the potential association between urinary MT levels and causes of mortality among residents of the Kakehashi River Basin who have been exposed to Cd. METHOD: The study involved a total of 1,398 men and 1,731 women were conducted between 1981 and 1982, with follow-up until November 2016. The study employed the Cox proportional-hazards model to examine the association between higher urinary MT concentrations and the risk of all-cause or cause-specific mortality within the population. Furthermore, the Fine and Gray competing risks regression model was used to evaluate the links between specific causes of death. RESULTS: The findings revealed that elevated urinary MT concentrations were linked to increased all-cause mortality and higher mortality rates from renal and urinary tract diseases across all participants. Specifically, in men, higher urinary MT levels were associated with elevated all-cause mortality, while in women, increased concentrations were linked to higher mortality from endocrine, nutritional, and metabolic diseases, as well as cardiovascular diseases. Even after adjusting for competing risks, higher urinary MT concentrations were associated with tumor-related mortality in men and continued to be associated with cardiovascular disease mortality in women. CONCLUSIONS In conclusion, the results suggest that women may face a greater risk of adverse health effects due to prolonged exposure to Cd. Urinary MT levels could potentially serve as a biomarker for mortality from these diseases in populations chronically exposed to Cd.
Humans ; Male ; Female ; Cadmium/urine* ; Japan/epidemiology* ; Metallothionein/metabolism* ; Middle Aged ; Cause of Death ; Adult ; Follow-Up Studies ; Aged ; Environmental Exposure/analysis* ; Proportional Hazards Models

BACKGROUND: To explore the associations of green tea, coffee, black tea, and oolong tea consumption with mortality from chronic kidney disease (CKD) as the underlying cause among Japanese adults. METHODS: We conducted a prospective cohort study of 110,585 men and women aged 40-79 years at recruitment from 1986 to 1990. Baseline information on the consumption of tea and coffee, lifestyles, and medical histories was obtained via self-administered questionnaires. We used multivariable Cox regression models to estimate sex-specific hazard ratios and 95% CIs of mortality from CKD associated with the consumption of green tea, coffee, black tea, or oolong tea. RESULTS: After a median 19-year follow-up, the hazard ratios of mortality from CKD in women were 0.49 (95% CI, 0.22-1.06) for 1-2 cups of green tea per day, 0.56 (0.31-0.99) for 3-4 cups per day, and 0.55 (0.32-0.93) for ≥5 cups per day, compared with <1 cup per day. No such association was found in men. Coffee, black tea, and oolong tea consumption were not associated with CKD risk in either sex. CONCLUSIONS Daily consumption of green tea was associated with a lower risk of mortality from CKD in women.
Humans ; Tea ; Coffee ; Middle Aged ; Male ; Female ; Japan/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; Aged ; Adult ; Prospective Studies ; Risk Factors ; Proportional Hazards Models ; East Asian People

BACKGROUND: Quick accomplishment and responsiveness are behaviors related to time management by perceived control of time, such as a positive feeling of using one's time well. In recent years, positive psychological states have been associated with a lower risk of cardiovascular disease (CVD). Thus, we investigated the associations of quick accomplishment and responsiveness with CVD mortality in a large cohort study. METHODS: The study participants were 75,049 (30,901 men and 44,148 women) aged 40-79 between 1988 and 1990 and followed until the end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality from CVD according to quick accomplishment, responsiveness, and their combination were calculated after adjustment for potential confounding factors using the Cox proportional hazard model. RESULTS: Quick accomplishment was associated with a lower risk of CVD mortality in women; a similar but marginally significant association was observed in men; the respective multivariable HR (95%CI) was 0.91 (0.83-0.99) and 0.93 (0.86-1.01). The presence of both quick accomplishment and responsiveness was associated with lower risk in men, which was confined to men aged 60-79; the respective multivariable HR (95%CI) was 0.88 (0.78-0.99) and 0.83 (0.72-0.96). CONCLUSIONS Quick accomplishment was associated with a lower risk of CVD mortality. Quick accomplishment and responsiveness combined were inversely associated with CVD mortality risk among older men.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/psychology* ; Cohort Studies ; Japan/epidemiology* ; Proportional Hazards Models ; Risk Factors ; East Asian People/psychology*

BACKGROUND: Cardiovascular disease (CVD) is the predominant cause of mortality in China. However, the mechanisms linking sarcopenia to CVD remain poorly understood, particularly in normal-weight populations. Individuals with the absence of overweight or obesity may tend to experience missed opportunities for timely intervention. This study aimed to investigate the longitudinal association between sarcopenia and incidence of new-onset CVD in a normal-weight population, and to examine the mediating effect of functional limitation in this relationship. METHODS: We conducted a closed-cohort analysis using a nationwide sample of 4,147 middle-aged and older adults with normal weight in China. We performed Cox proportional hazards regression analysis to explore the associations of baseline sarcopenia with incident CVD. The difference method was applied to estimate the mediation proportion of functional limitation in this association. RESULTS: Over a mean follow-up period of 7.62 years, CVD occurred in 835 participants. In the multivariable-adjusted Cox model, individuals with sarcopenia exhibited a significantly higher likelihood of developing incident CVD compared to those without sarcopenia (adjusted hazard ratio [aHR] = 1.45, 95% confidence interval [CI]: 1.21-1.73, P < 0.001). Similar associations were observed for the incidence of heart disease and stroke. Functional limitation accounted for approximately 15.0% of the total effect of sarcopenia on incident CVD (P < 0.001). CONCLUSIONS Sarcopenia exerts both direct and indirect effects on incident CVD among middle-aged and older adults who are normal weight, with functional limitation serving as a significant mediator. Interventions targeting both sarcopenia and functional limitation may offer a promising strategy for enhancing cardiovascular health in this population.
Humans ; Sarcopenia/complications* ; China/epidemiology* ; Male ; Female ; Middle Aged ; Cardiovascular Diseases/etiology* ; Aged ; Incidence ; Cohort Studies ; Proportional Hazards Models ; Risk Factors ; Aged, 80 and over ; Longitudinal Studies

BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*

OBJECTIVE: To investigate the expression and possible regulatory mechanism of miR-34a in the lung tissue of neonatal rat model of bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: In the study, 80 newborn SD rats were randomly divided into hyperoxia group (FiO₂=60%) and air group (FiO₂=21%) within 2 hours after birth, 40 rats per group. Lung tissue samples of the SD rats in each group were extracted on the 1st, 7th, 14th and 21st days after birth, and the pathological changes of lung tissue were observed under light microscope after HE staining. The number of radial alveolar counts (RAC) and the mean alveolar diameter (MAD) and the thickness of alveolar septal thickness (AST) were measured to evaluate the development of alveoli. Real-time fluorescence quantitative PCR was used to detect the expression of miR-34a, angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) in lung tissue of rats in hyperoxia group and air group at different time points. Enzyme-linked immunosorbent assay (ELISA) was used to detect the proteins expression of Ang-1 and Tie-2 in the lung tissues of the two groups at different time points. RESULTS: The weight of rats in the hyperoxia group on the 7th, 14th and 21st days after birth was significantly lower than that in the air group (P all < 0.05). With the prolongation of oxygen exposure, the number of alveoli decreased, the volume increased, the structure simplified, the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group. On the 7th, 14th and 21st days after birth, the RAC in the hyperoxia group was significantly lower than that in the air group (P all < 0.05). Compared with the air group, MAD and AST increased significantly on the 7th, 14th and 21st days after birth in the hyperoxia group, and the difference was statistically significant (P all < 0.05). The expression level of miR-34a in lung tissue of hyperoxia group was significantly higher than that of air group on the 7th, 14th and 21st days after birth, and the difference was statistically significant (P all < 0.05). Compared with the air group at the same time point, the expression levels of Ang-1 and Tie-2 mRNA and protein in the hyperoxia group were lower than those in the air group on the 14th and 21st days after birth (P all < 0.05). CONCLUSION The new BPD model of newborn SD rats can be successfully established by continuous exposure to 60% hyperoxia. The expression of miR-34a was up-regulated in the lung tissue of the new BPD model of neonatal rats. MiR-34a may play an important role in the occurrence and development of BPD by regulating Ang-1/Tie-2 signal pathway.
Animals ; MicroRNAs/metabolism* ; Bronchopulmonary Dysplasia/genetics* ; Hyperoxia/metabolism* ; Rats, Sprague-Dawley ; Animals, Newborn ; Rats ; Angiopoietin-1/genetics* ; Disease Models, Animal ; Receptor, TIE-2/genetics* ; Lung/pathology* ; Male

This study evaluated the healing-promoting effect and applicability of seven new dressings in chronic wounds. A chronic wound model was established using 48 db/db diabetic mice, which were randomly divided into 8 groups (control, polymer film, alginate, foam, hydrocolloid, hydrogel, carbon fiber, and silver dressing groups). Regular monitoring was conducted on the 5, 10, 15, and 20 days after surgery, and a comprehensive evaluation was performed based on healing rate, characteristic of histopathology, and semi-quantitative scoring. The results showed that, except for the polymer film dressing group, all other dressing groups had significantly better healing-promoting effect than the control group ( P＜0.05), with the hydrocolloid, carbon fiber, and silver dressing groups demonstrated particularly outstanding efficacy. This study systematically compared the efficacy differences of seven dressings, and combined them with the adhesion, exudate volume and infection risks to provide a scientific basis for clinical dressing selection.
Animals ; Mice ; Wound Healing ; Bandages ; Male ; Diabetes Mellitus, Experimental ; Disease Models, Animal