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:To evaluate the effectiveness and safety of 3D simultaneous dual fluorescence imaging using indocyanine green(ICG)and methylene blue(MB)in surgeries for malignant uterine tumors.Methods:37 patients who underwent surgery for cervical or endometrial cancer at Guangxi Medical University Cancer Hospital from April 16,2024 to July 19,2024 were included.All patients received simultaneous fluorescence imaging using ICG and MB during surgery.ICG was injected into the cervix for sentinel lymph node(SLN)imaging,and MB was intravenously administered for ureteral imaging.3D fluorescence laparoscopy was used for simultaneous dual fluo-rescence imaging,and the accuracy of localization,signal quality,and clinical effectiveness were assessed using the Likert scale.Adverse events were monitored,and postoperative follow-up was conducted.Results:The SLN visualization rate was 100.0％,and the ureteral visualization rate was 97.3％.The average start time for SLN ima-ging was 4.08±0.64 min after ICG injection,while the average start time for ureteral imaging was 44.86±5.42 min after intravenous MB administration.The main locations of SLN included:internal iliac(13.5％),external iliac(32.4％),and obturator(67.6％).The localization accuracy and signal quality Likert scores of ICG were 4.59±0.45 points and 4.57±0.50 points,respectively;MB were 4.37±0.88 points and 4.28±0.91 points,respectively.There was no ureteral injury during the operation,no urinary fistula after the operation,and no serious adverse e-vents related to the contrast agents were reported.Conclusions:The 3D simultaneous dual fluorescence imaging technique is highly feasible and safe in surgeries for cervical and endometrial cancers.It can effectively locate SLNs and visualize the ureters,simplify the surgical process and reduce difficulty.This technique provides a new auxiliary method for surgeries involving malignant uterine tumors,with promising clinical application prospects.

In the treatment of high-risk and extremely high-risk localized prostate cancer，urologists，radiation therapists and oncologists have different opinions. With the development of new systemic therapy drugs and the application of genetic testing，treatment methods are constantly evolving. This article reviews the latest research progress，including radical prostatectomy，lymph node dissection，radiotherapy，and systemic treatment regimens (docetaxel-based therapy，novel endocrinotherapy，immunotherapy，targeted therapy)，to systematically evaluate the long-term survival and tumor control efficacy of different treatment methods，so as to provide clinical reference.

Objective:To evaluate the effectiveness and safety of 3D simultaneous dual fluorescence imaging using indocyanine green(ICG)and methylene blue(MB)in surgeries for malignant uterine tumors.Methods:37 patients who underwent surgery for cervical or endometrial cancer at Guangxi Medical University Cancer Hospital from April 16,2024 to July 19,2024 were included.All patients received simultaneous fluorescence imaging using ICG and MB during surgery.ICG was injected into the cervix for sentinel lymph node(SLN)imaging,and MB was intravenously administered for ureteral imaging.3D fluorescence laparoscopy was used for simultaneous dual fluo-rescence imaging,and the accuracy of localization,signal quality,and clinical effectiveness were assessed using the Likert scale.Adverse events were monitored,and postoperative follow-up was conducted.Results:The SLN visualization rate was 100.0％,and the ureteral visualization rate was 97.3％.The average start time for SLN ima-ging was 4.08±0.64 min after ICG injection,while the average start time for ureteral imaging was 44.86±5.42 min after intravenous MB administration.The main locations of SLN included:internal iliac(13.5％),external iliac(32.4％),and obturator(67.6％).The localization accuracy and signal quality Likert scores of ICG were 4.59±0.45 points and 4.57±0.50 points,respectively;MB were 4.37±0.88 points and 4.28±0.91 points,respectively.There was no ureteral injury during the operation,no urinary fistula after the operation,and no serious adverse e-vents related to the contrast agents were reported.Conclusions:The 3D simultaneous dual fluorescence imaging technique is highly feasible and safe in surgeries for cervical and endometrial cancers.It can effectively locate SLNs and visualize the ureters,simplify the surgical process and reduce difficulty.This technique provides a new auxiliary method for surgeries involving malignant uterine tumors,with promising clinical application prospects.

Objective:To study the expression of methyltransferase-like protein 14 (METTL14) in epithelial ovarian cancer and its clinical significance, and to explore the effect of METTL14 expression on the proliferation, invasion and migration of ovarian cancer cells.Methods:Immunohistochemistry (IHC) was used to detect METTL14 expression in tumor tissue samples, and analyze the relationships among METTL14 expression, clinicopathological factors, and prognosis in ovarian cancer. Lentiviral vectors and small interfering RNA (siRNA) were used to up-regulate and down-regulate the METTL14 expression in ovarian cancer cell lines A2780 and SKOV3, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to detect the N6-methyladenosine (m6A) content in ovarian cancer cells. Cell counting kit-8 (CCK-8), wound healing assay, and transwell assay were used to examine the function of METTL14 expression in the cells.Results:(1) The IHC score of METTL14 protein was 6.2±3.7 in 20 samples of ovarian cancer tissues and 3.3±2.5 in 15 samples of normal ovarian tissues, and the difference was statistically significant ( t=-2.64, P=0.012). Among the patients who suffered from ovarian cancer, there were 69 cases with high expression of METTL14 protein (IHC score≥6), accounting for 57.0% (69/121), and the cases with low expression of METTL14 protein (IHC score<6) accounting for 43.0% (52/121). Compared with the patients with low expression of METTL14, the patients with high expression of METTL14 had later stages, higher rates of lymph node metastasis, abdominal metastasis, and more ascite amount. The differences were statistically significant (all P<0.05). The overall survival rate was significantly lower in patients with high METTL14 expression than the low expression ( P=0.009). (2) LC-MS/MS data showed that the relative expression of m6A in A2780 and SKOV3 cells in the lentivirus (LV)-METTL14 group were 0.213±0.024 and 0.181±0.018, which were significantly higher than those in the LV-normal control (NC) group (0.109±0.022 and 0.128±0.020; all P<0.05). While the relative expression of m6A in A2780 and SKOV3 cells in the si-METTL14 group were 0.063±0.012 and 0.069±0.015, which were significantly lower than the expression in si-NC group of 0.108±0.014 and 0.121±0.014 (all P<0.05). CCK-8 assay showed that the absorbance values were significantly lower in the si-METTL14 group compared with the si-NC group at 36, 48, 60 hours (all P<0.05); while were significantly increased in the LV-METTL14 group compared with the LV-NC group at 48, 60 hours (all P<0.01). Scratch wound assays showed that the migration rate of the si-METTL14 group was lower than those of the si-NC group, while the LV-METTL14 group were higher than the LV-NC group by 24 hours, the differences were statistically significant (all P<0.01). Cell migration and invasion were detected by transwell migration and invasion assays. After cultivated for 24 hours, the invasion cell number and the migration cell number in the si-METTL14 group were less than those in the si-NC group. While the invasion cell number and the migration cell number in the LV-METTL14 group were more than those in the LV-NC group, respectively. The differences were statistically significant (all P<0.01). Conclusion:Patients with high METTL14 expression have a worse prognosis in ovarian cancer, which may increase the m6A modification of ovarian cancer cells and promote cells proliferation, invasion and migration.

Objective:To explore the effect of previous intestinal resection on anastomotic fistula within 30 days after surgery in Crohn′s disease.Methods:The clinical data from 92 Crohn′s disease patients who underwent intestinal resection and anastomosis at the Department of General Surgery in Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine from Jan 2016 to Sep 2019. Patients were divided into no previous intestinal resection group ( n=45) and previous intestinal resection group ( n=47). The relationship between previous intestinal resection and postoperative anastomotic leak in Crohn′s disease patients with intestinal resection and anastomosis was analyzed. Results:A total of 11 cases (12% leak rate) underwent postoperative anastomotic leak. There were 2 leaks in patients with no previous history of intestinal resection, while 9 leaks in patients with previous bowel resection (χ 2 =4.722, P=0.03). The OR of the postoperative anastomotic leak in Crohn′s disease patients with previous intestinal resection compared with no previous intestinal resection group was 5.092 (95% CI: 1.035-25.048). Patients with 1 previous resection (24 cases) had a leak rate of 13%, whereas patients with >1 previous resection episodes (23 cases) had a leak rate of 26%. The number of previous resection episodes correlated with an increasing risk for clinical anastomotic leak (correlation coefficien r=0.995). Conclusions:Previous intestinal resection is an independent risk factor for ensuing postoperative anastomotic leak in Crohn′s disease patients with intestinal resection and anastomosis.

Objective:To investigate the feasibility of near-infrared fluorescence imaging (NIRFI) to assist in determining the resection range of radiation intestinal injury (RII).Methods:A descriptive cohort study was conducted. Clinical data of 10 RII patients who presented intestinal obstruction and received operation with more than 100 cm of small intestine had been resected atGeneral Department of Jinling Hospital from October 2014 to January 2015 were retrospectively analyzed. The Novadaq SPY Intra-operative Imaging System was used in capturing and viewing fluorescent images. Firstly, the dense adhesion was mobilized and the obstructive intestine was fully freed under laparoscopy, then entering into abdomen from the corresponding incision. The surgeon determined the resection range according to the color of the intestinal serous layer of the diseased intestinal wall, the thickness of the intestinal wall, and the degree of swelling of the mesentery. Afterwards, intra-operative NIRFI was performed by intravenous injection of 2 ml indocyanine green (ICG) and the imaging results of the diseased intestinal arteriovenous phase were observed and recorded. The evaluation criteria for the final resection range were mainly based on the changes in mesenteric arterial phase imaging. In RII lesions, mesenteric vessels in mesenteric artery phase were disordered, and the comb-like distribution of normal mesenteric vessels completely disappeared. Only the clouded appearance in the intestinal wall was observed. Imaging results of the diseased intestinal tissue during the development phase and mesenteric vein phase were not significantly different from normal intestinal tissue. Intraoperative and postoperative conditions under NIRFI-assisted positioning, including the resection range, anastomosis site, operation-related complications, hospitalization time and cost were recorded. Data of abdominal contrast-enhanced CT and gastrointestinal angiography during 5 years of follow-up were collected to evaluate whether there was anastomotic stenosis or insufficient resection of diseased bowel.Results:Based on the imaging of mesenteric arterial phase of NIRFI, the median resection length of the small intestine was 185 (120-260) cm. After NIRFI imaging, only local lesion of ileum was excised in 6 patients, and jejunum-ileum anastomosis was performed to preserve ileocecal flap. No serious complications such as anastomotic leakage and anastomotic hemorrhage, or chronic intestinal failure such as short bowel syndrome occurred. The median hospitalization time was 32 (22-51) days, and the median hospitalization cost was 142 000 (90 000-175 000) RMB. The hospitalization time and cost were mainly used for the enteral and parenteral nutrition support treatment during the perioperative period. All the patients had normal oral diet and/or oral enteral nutrient. After 5 years of follow-up, no recurrence was found. Abdominal contrast-enhanced CT and gastrointestinal angiography showed no thickening of the intestinal wall or stenosis of the lumen.Conclusion:Mesenteric arterial phase imagingof NIRFI can help surgeons to determine the site and range of resection of RII lesions.

Objective:To investigate the feasibility of near-infrared fluorescence imaging (NIRFI) to assist in determining the resection range of radiation intestinal injury (RII).Methods:A descriptive cohort study was conducted. Clinical data of 10 RII patients who presented intestinal obstruction and received operation with more than 100 cm of small intestine had been resected atGeneral Department of Jinling Hospital from October 2014 to January 2015 were retrospectively analyzed. The Novadaq SPY Intra-operative Imaging System was used in capturing and viewing fluorescent images. Firstly, the dense adhesion was mobilized and the obstructive intestine was fully freed under laparoscopy, then entering into abdomen from the corresponding incision. The surgeon determined the resection range according to the color of the intestinal serous layer of the diseased intestinal wall, the thickness of the intestinal wall, and the degree of swelling of the mesentery. Afterwards, intra-operative NIRFI was performed by intravenous injection of 2 ml indocyanine green (ICG) and the imaging results of the diseased intestinal arteriovenous phase were observed and recorded. The evaluation criteria for the final resection range were mainly based on the changes in mesenteric arterial phase imaging. In RII lesions, mesenteric vessels in mesenteric artery phase were disordered, and the comb-like distribution of normal mesenteric vessels completely disappeared. Only the clouded appearance in the intestinal wall was observed. Imaging results of the diseased intestinal tissue during the development phase and mesenteric vein phase were not significantly different from normal intestinal tissue. Intraoperative and postoperative conditions under NIRFI-assisted positioning, including the resection range, anastomosis site, operation-related complications, hospitalization time and cost were recorded. Data of abdominal contrast-enhanced CT and gastrointestinal angiography during 5 years of follow-up were collected to evaluate whether there was anastomotic stenosis or insufficient resection of diseased bowel.Results:Based on the imaging of mesenteric arterial phase of NIRFI, the median resection length of the small intestine was 185 (120-260) cm. After NIRFI imaging, only local lesion of ileum was excised in 6 patients, and jejunum-ileum anastomosis was performed to preserve ileocecal flap. No serious complications such as anastomotic leakage and anastomotic hemorrhage, or chronic intestinal failure such as short bowel syndrome occurred. The median hospitalization time was 32 (22-51) days, and the median hospitalization cost was 142 000 (90 000-175 000) RMB. The hospitalization time and cost were mainly used for the enteral and parenteral nutrition support treatment during the perioperative period. All the patients had normal oral diet and/or oral enteral nutrient. After 5 years of follow-up, no recurrence was found. Abdominal contrast-enhanced CT and gastrointestinal angiography showed no thickening of the intestinal wall or stenosis of the lumen.Conclusion:Mesenteric arterial phase imagingof NIRFI can help surgeons to determine the site and range of resection of RII lesions.

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CCl₄ (a mixture of pure CCl₄ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)₂D₃(0.5 µg/100 g) and the vehicle were administered simultaneously with CCl₄ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CCl₄-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.
Animals ; Apoptosis ; Bacterial Translocation ; Cholestasis ; Enterocytes ; Fibrosis ; Heme Oxygenase-1 ; Heme ; Humans ; Liver ; Liver Diseases ; Olive Oil ; Oxidative Stress ; Rats ; Tight Junctions ; Vitamin D ; Vitamins

Background:Although sustainable control since 1950s has achieved great successes,schistosomiasis japonica remains a major public health problem in China.Since 2004,a new integrated strategy was developed aiming to control the transmission of Schistosoma japonicum through the implementation of a package of interventions.To date,no systematic review or meta-analysis assessing the effectiveness of this new integrated strategy for schistosomiasis control in China has been published.We performed a PubMed-based bibliometric assessment of publications on the new integrated strategy for schistosomiasis japonica control in China,to understand the global transmissibility and sharing of the new integrated strategy.Methods:An in-depth bibliometric analysis of all publications on the new integrated strategy for schistosomiasis japonica control in China was performed through a PubMed search using the terms "schistosomiasis" and "China,"from January 1,2004 to August 31,2018.All titles and abstracts were read carefully,and the publications reporting the effectiveness,experiences,lessons,or problems of the new integrated strategy were included in the bibliometric analysis.Results:Overall,2,361 titles were screened,and 70 eligible publications were accessed for analyses,including 23 studies in English,published in 15 international journals,and 47 studies in Chinese with abstracts in English,published in 3 national journals.Chinese Journal of Schistosomiasis Control (Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi) published 60％ of the research output,Research articles (48.6％) and short reports (37.1％) were the dominant manuscript types.Furthermore,471 contributing authors from 277 affiliations across 9 countries produced these 70 publications.Conclusion:This is the first PubMed-based quantitative analysis of the research output of the new integrated strategy,and our data indicate a low global transmissibility of Chinese new integrated strategy.We therefore call for more research outputs of the new integrated strategy for schistosomiasis japonica control in China to be communicated through international platforms.