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

The obesity problem is becoming increasingly severe,posing greater challenges to the prevention and control of chronic diseases and the implementation of the Healthy China Strategy.Based on national policy require-ments such as the Implementation Plan for the"Weight Management Year"Activity and the Notice on the Setup and Manage-ment of Healthy Weight Management Clinics,it analyzes the functional positioning of healthy weight management clinic in public hospitals.It explores operational mechanisms through key elements including disciplinary integration,staffing,equipment,space,as well as the process design of standardized,full-process,multidisciplinary comprehensive management.Finally,it proposes policy recommendations for standardizing the establishment of healthy weight management outpatient department in public hospitals.

The obesity problem is becoming increasingly severe,posing greater challenges to the prevention and control of chronic diseases and the implementation of the Healthy China Strategy.Based on national policy require-ments such as the Implementation Plan for the"Weight Management Year"Activity and the Notice on the Setup and Manage-ment of Healthy Weight Management Clinics,it analyzes the functional positioning of healthy weight management clinic in public hospitals.It explores operational mechanisms through key elements including disciplinary integration,staffing,equipment,space,as well as the process design of standardized,full-process,multidisciplinary comprehensive management.Finally,it proposes policy recommendations for standardizing the establishment of healthy weight management outpatient department in public hospitals.

Background:With the development of medical technology,cholangioscopy has been increasingly utilized in the diagnostic and therapeutic process of endoscopic retrograde cholangiopancreatography(ERCP).They play a significant role in the visual diagnosis and biopsy of tumors,providing more accurate and detailed information for clinicians.Aims:To evaluate the safety and effectiveness of peroral cholangioscopy combined with ERCP in biliary diseases.Methods:A total of 90 cases underwent peroral cholangioscopy and ERCP from October 2022 to October 2023 at Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine were recruited retrospectively,and the clinical data were collected.The success rate,postoperative complications,and other relevant indicators were evaluated.Results:A total of 90 patients were enrolled,the preoperative diagnosis including common bile duct stones(43 cases),biliary obstruction by tumor invasion(21 cases),benign biliary stenosis(15 cases),benign ampullary tumors(6 cases),postoperative biliary stricture after liver transplantation(3 cases),primary sclerosing cholangitis(1 case),and biliary varices(1 case).The technical success rate of peroral cholangioscopy with ERCP was 100%,and the stone removal rate was 95.3%(41/43),the average operation time was(81±37)min,and the ERCP re-intervention rate within six months was 17.8%.Postoperative complications included fever(7.8%),abdominal pain(3.3%),bleeding/anemia(2.2%),and postoperative pancreatitis(2.2%).Conclusions:The combination of peroral cholangioscopy with ERCP is safe and effective for the biliary diseases with no increase in procedure-related adverse events and risks.

In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma， this article systematically analyzes the historical evolution of the name， origin， harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica， prescription books， medical books and modern literature. The research results showed that Baiji（白及） was the main name， some scholars took Baiji（白芨） as its main name， and there were many other names such as Baiji（白给）， Baigen（白根）， Baiji（白苙）. The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata， and drying， large， white， solid， root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials， there were certain differences between their traits， and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed， with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn， and harvested in autumn was better. The processing and processing technology is relatively simple， and it was used fresh or powdered in past dynasties， while it is mainly sliced for raw use in modern times. Based on the results， it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas， and it should be uniformly written as Baiji（白及）. And if the original formula indicates the requirement of processing， it should be operated according to the requirement， if the requirement of processing is not indicated， it can be used in raw form as medicine.

Background:With the development of medical technology,cholangioscopy has been increasingly utilized in the diagnostic and therapeutic process of endoscopic retrograde cholangiopancreatography(ERCP).They play a significant role in the visual diagnosis and biopsy of tumors,providing more accurate and detailed information for clinicians.Aims:To evaluate the safety and effectiveness of peroral cholangioscopy combined with ERCP in biliary diseases.Methods:A total of 90 cases underwent peroral cholangioscopy and ERCP from October 2022 to October 2023 at Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine were recruited retrospectively,and the clinical data were collected.The success rate,postoperative complications,and other relevant indicators were evaluated.Results:A total of 90 patients were enrolled,the preoperative diagnosis including common bile duct stones(43 cases),biliary obstruction by tumor invasion(21 cases),benign biliary stenosis(15 cases),benign ampullary tumors(6 cases),postoperative biliary stricture after liver transplantation(3 cases),primary sclerosing cholangitis(1 case),and biliary varices(1 case).The technical success rate of peroral cholangioscopy with ERCP was 100%,and the stone removal rate was 95.3%(41/43),the average operation time was(81±37)min,and the ERCP re-intervention rate within six months was 17.8%.Postoperative complications included fever(7.8%),abdominal pain(3.3%),bleeding/anemia(2.2%),and postoperative pancreatitis(2.2%).Conclusions:The combination of peroral cholangioscopy with ERCP is safe and effective for the biliary diseases with no increase in procedure-related adverse events and risks.

Objective To investigate the neuroprotective effect of methylene blue on diabetic retinopathy in rats. Methods Thirty SD rats were randomly divided into blank, control and experimental groups. The control and experimental groups were induced with diabetes by streptozotocin (STZ) intraperitoneal injection. After 6 weeks of successful modeling, the experimental group received intravitreal injection of methylene blue at a dose of [0.2 mg/(kg.d)], while the control group received an equal amount of dimethyl sulfoxide (DMSO) intravitreal injection, both continuously injected for 7 days. ELISA was used to detect the levels of retinal superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (iPF2α) and interleukin-1β (IL-1β) in rats. Western blot analysis was used to detect the expression of retinal extracellular signal-regulated kinase 1/2 phosphorylation (p-ERK1/2) and phosphorylated protein kinase B (p-AKT), and PAS staining was used to detect retinal morphological changes. Results Compared with the blank group rats, the retinal SOD activity in the control and experimental group rats was significantly reduced. iPF2α, IL-1β and p-ERK1/2 level increased, while p-AKT level decreased. Compared with the control group, the SOD activity of the experimental group rats increased. iPF2α and IL-1β level went down, while p-ERK1/2 and p-AKT level went up significantly. The overall thickness of the retinal layer and the number of retinal ganglion cells were significantly reduced. Conclusion Methylene blue improves diabetic retinopathy in rats by reducing retinal oxidative stress and enhancing ERK1/2 and AKT phosphorylation.
Rats ; Animals ; Diabetic Retinopathy/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mitogen-Activated Protein Kinase 3/metabolism* ; Interleukin-1beta/metabolism* ; Methylene Blue/pharmacology* ; Phosphorylation ; Rats, Sprague-Dawley ; MAP Kinase Signaling System ; Diabetes Mellitus, Experimental/drug therapy* ; Superoxide Dismutase/metabolism*

Background: Unintended intraoperative hypothermia is a common complication of general anesthesia surgery, which can cause pain, coagulation dysfunction, wound infection, delayed recovery, and other adverse consequences. There are few studies related to intraoperative hypothermia during endoscopic retrograde cholangiopancreatography (ERCP). Aims: To analyze the risk factors of intraoperative hypothermia during ERCP under general anesthesia and establish a predictive model. Methods: A total of 121 patients underwent ERCP under general anesthesia from September 2021 to November 2021 at Shanghai General Hospital were recruited, and relevant clinical data were collected. Logistic regression analysis was used to screen risk factors, and a predictive model was constructed. The model was externally validated by independent datasets with ROC curve and Hosmer⁃Lemeshow goodness of fit test. Results: A total of 114 patients were enrolled in modeling group. The incidence of intraoperative hypothermia was 11.40% (13/114). There were more women in the hypothermia group (P<0.05). The temperature of entering the operating room and operating room temperature were relatively lower in the hypothermia group (P<0.05). Gender was an independent risk factor for intraoperative hypothermia in ERCP under general anesthesia (P<0.05). The predictive model constructed by using gender and temperature of entering the operating room screened by Logistic regression analysis had a good discrimination and calibration, area under the ROC curve by external validation was 0.78. Conclusions: Gender and temperature of entering the operating room can effectively predict the occurrence of intraoperative hypothermia and assist perioperative monitoring and management.

Objective:To investigate the effects of metformin on the survival of patients with advanced non-small cell lung cancer (NSCLC).Methods:PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and other databases were searched from the beginning of database construction to February 2020, relevant literatures were screened and included, and the characteristics of the literatures were extracted. RevMan 5.3 software was used to analyze progression-free survival (PFS), overall survival (OS), hazard ratio(HR) and 95% CI; the heterogeneity and publication bias were also evaluated. Results:A total of 11 studies were enrolled, and metformin did not improve PFS in patients with advanced NSCLC ( HR = 0.80, 95% CI 0.58-1.09, P = 0.15). The subgroup analysis results of different treatment strategies showed that metformin combined with tyrosine kinase inhibitor (TKI) ( HR = 0.71, 95% CI 0.32-1.57, P = 0.39), chemoradiotherapy ( HR = 0.97, 95% CI 0.59-1.61, P = 0.92), and immune checkpoint inhibitor (ICI) ( HR = 0.64, 95% CI 0.35-1.16, P = 0.14) did not improve the PFS. Metformin improved OS in patients with advanced NSCLC ( HR = 0.84, 95% CI 0.75-0.93, P = 0.001). Metformin combined with TKI ( HR = 0.68, 95% CI 0.38- 1.22, P = 0.19) and ICI ( HR =0.80, 95% CI 0.39-1.63, P = 0.54) did not improve OS of patients, while metformin combined with chemoradiotherapy could improve OS ( HR = 0.85, 95% CI 0.78-0.93, P < 0.01). No evidence of publication bias was shown in the funnel plot analysis. Conclusions:Metformin can prolong OS time in patients with advanced NSCLC, especially in patients undergoing metformin combined with radiotherapy and chemotherapy, or concurrent chemoradiotherapy.

Objective To screen the critical genes related to the development of esophageal squamous cell carcinoma ( ESCC ) by weighted gene co-expression network analysis ( WGCNA ) and to verify by experiments.Methods Gene expression data of ESCC were downloaded from gene expression omnibus (GEO) database based on gene chip platform ( GPL) 570, GPL571, GPL96/97 or GPL14613 platform, respectively. Meanwhile, the obtained differentially expressed genes together with gene expression data of 81 ESCC patients from the cancer genome atlas ( TCGA ) and clinical data were analyzed by WGCNA to set up co-expression networks including mRNA and microRNA ( miRNA ) . The expression of miRNA in ESCC tissues and paracancerous tissues was examined by quantitative real-time polymerase chain reaction ( RT-PCR ) .And the expression of target protein Kruppel like factor 4 ( KLF4 ) and desmocollin 2 ( DSC2 ) were detected by immunohistochemistry .After ESCC cell line ECA-109 cells were transfected with miRNA-92b-3p mimic, cell cycle was tested by flow cytometry ,the cell invasion and migration ability was measured by Transwell chamber assay and scratch-wound assay.The expression of KLF4 and DSC2 was observed by confocal laser scanning microscopy and Western blotting .The target genes were verified by luciferase assay .T-test, rank sum test, chi-square test and Pearson correlation analysis were performed for statistical analysis .Results A total of 4023 differential expression gene ( DEG) and 328 differential expression miRNA ( DEM) were screened and 11 gene modules were set up by WGCNA .Among them, the brown modules were negatively associated with tumor grade and T stage (r=-0.340 and -0.268, P=0.002 and 0.016).Meanwhile, has-miR-92b and the potential target genes KLF4 and DSC2 were all in the brown module .Furthermore, the results of RT-PCR showed the expression of miRNA-92b-3p in ESCC tissues was higher than that in paracancerous tissues (3.052(1.652, 5.371) vs.0.985(0.558, 2.032)), and the difference was statistically significant (Z=-4.021,P<0.01). The results of immunohistochemistry demonstrated that the positive rates of KLF 4 and DSC2 in ESCC tissues were 43.3％(13/30) and 20.0％(6/30), respectively, which were lower than those of paracancerous tissues (70.0％(21/30) and 63.3％(19/30)), and the differences were statistically significant (χ2 =4.344 and 1.589, both P<0.05).After ECA-109 cells were transfected with miRNA-92b-3p mimics, the percentage of cells at G0/G1 phase decreased ((63.71 ±2.83)％vs.(54.62 ±4.00)％) and the percentage of cells at the S phase and G2/M phase increased ((31.81 ±2.88)％vs.(41.20％±2.87)％, and (3.87 ±1.75)％vs. (8.10 ±1.71)％, respectively), and the differences were statistically significant (t =3.215, 4.000 and 2.998;P=0.032, 0.016 and 0.040).The invasion and migration ability of the cells were significantly improved (79.67 ±27.54 vs.280.33 ±46.18, (69.72 ±3.91)％ vs.(84.90 ±5.25)％), and the differences were statistically significant (t=6.465 and 4.019, P=0.003 and 0.016).The results of Western blotting indicated that, compared with control mimic group , the expression of KLF4 and DSC2 was both dramatically downregulated after transfected with miRNA-92b-3p mimics transfected (1.00 ±0.23 vs.0.42 ±0.03, 1.00 ±0.20 vs.0.55 ± 0.21), and differences were statistically significant (t=4.470 and 5.493, P=0.042 and 0.032).The results of luciferase assay demonstrated that miRNA-92b-3p could directly bind KLF4 and DSC2. Conclusion WGCNA is an efficient systemic biological approach by which miRNA-92b-3p is identified as a new cancer-promoting gene .