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 investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

OBJECTIVE: To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT). METHODS: Three pregnant women who underwent NIPT testing at Guangdong Women and Children's from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethics No.: 20230132). RESULTS: Case 1 underwent selective fetal reduction at 8⁺ weeks of gestation. At 17⁺ weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks' gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 (Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13⁺ weeks due to fetal abnormalities in one twin. At 22⁺ weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable. CONCLUSION In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.
Adult ; Female ; Humans ; Pregnancy ; Diseases in Twins/diagnosis* ; Karyotyping ; Noninvasive Prenatal Testing/methods* ; Pregnancy, Twin ; Prenatal Diagnosis/methods*

Objective:To evaluate the diagnostic performance of 64Cu-prostate specific membrane antigen (PSMA)-Q compared with 18F-FDG in patients with advanced prostate cancer and to analyze the radiation dosimetry of 64Cu-PSMA-Q. Methods:This study was an open-label, single-arm, self-controlled diagnostic evaluation trial. A total of 29 patients (age 58-87 years) with pathologically confirmed advanced prostate cancer in the Affiliated Hospital of North Sichuan Medical College from September 2023 to December 2023 were included. All patients underwent both 64Cu-PSMA-Q PET/CT and 18F-FDG PET/CT examinations. McNemar test was used to compare the detection rates of 64Cu-PSMA-Q PET/CT and 18F-FDG PET/CT for primary lesions, lymph node metastases, and bone metastases. Mann-Whitney U test was applied to compare differences in SUV max and tumor-to-background ratio (TBR) between 64Cu-PSMA-Q PET/CT and 18F-FDG PET/CT. Radiation dosimetry of 64Cu-PSMA-Q PET/CT imaging was performed using OLINDA/EXM 2.1 (adult male model) in 9 patients. Results:Primary lesions were detected in 21 patients. 64Cu-PSMA-Q PET/CT demonstrated a detection rate of 95.2%(20/21) for primary lesions, which was significantly higher than that of 18F-FDG PET/CT (66.7%(14/21); χ2=6.00, P=0.031). Detection rates of lymph node metastases were 65.5%(19/29) for 64Cu-PSMA-Q and 55.2%(16/29) for 18F-FDG, with no significant difference ( χ2=3.00, P=0.250). Similarly, detection rates of bone metastases were 72.4%(21/29) for 64Cu-PSMA-Q and 65.5%(19/29) for 18F-FDG respectively ( χ2=2.00, P=0.500). TBRs on 64Cu-PSMA-Q PET/CT were significantly higher than those on 18F-FDG PET/CT across primary lesions (8.3(2.2, 13.3) vs 2.3(1.0, 5.5); Z=7.16, P=0.002), regional lymph node metastases (4.9(1.4, 8.3) vs 1.7(0.9, 4.0), Z=189.34, P=0.001), and bone metastases (18.7(4.5, 26.9) vs 5.1(2.1, 9.7); Z=24.83, P=0.003). No significant difference in TBR was observed for distant lymph node metastases ( Z=1.49, P=0.135) or benign lesions ( Z=0.91, P=0.558). The whole-body effective dose of 64Cu-PSMA-Q was (28.200±1.590)μSv/MBq among the 9 patients analyzed, with no adverse events related to the tracer observed. Conclusion:64Cu-PSMA-Q is a promising novel PET imaging agent with potential clinical utility for diagnosing prostate cancer and supporting clinical decision-making.

Objective:To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT).Methods:Three pregnant women who underwent NIPT testing at Guangdong Women and Children′s from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethic No.: 20230132).Results:Case 1 underwent selective fetal reduction at 8 + weeks of gestation. At 17 + weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks′ gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 ( Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13 + weeks due to fetal abnormalities in one twin. At 22 + weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable. Conclusion:In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.

Objective:To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT).Methods:Three pregnant women who underwent NIPT testing at Guangdong Women and Children′s from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethic No.: 20230132).Results:Case 1 underwent selective fetal reduction at 8 + weeks of gestation. At 17 + weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks′ gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 ( Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13 + weeks due to fetal abnormalities in one twin. At 22 + weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable. Conclusion:In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.

Objective:To evaluate the diagnostic performance of 64Cu-prostate specific membrane antigen (PSMA)-Q compared with 18F-FDG in patients with advanced prostate cancer and to analyze the radiation dosimetry of 64Cu-PSMA-Q. Methods:This study was an open-label, single-arm, self-controlled diagnostic evaluation trial. A total of 29 patients (age 58-87 years) with pathologically confirmed advanced prostate cancer in the Affiliated Hospital of North Sichuan Medical College from September 2023 to December 2023 were included. All patients underwent both 64Cu-PSMA-Q PET/CT and 18F-FDG PET/CT examinations. McNemar test was used to compare the detection rates of 64Cu-PSMA-Q PET/CT and 18F-FDG PET/CT for primary lesions, lymph node metastases, and bone metastases. Mann-Whitney U test was applied to compare differences in SUV max and tumor-to-background ratio (TBR) between 64Cu-PSMA-Q PET/CT and 18F-FDG PET/CT. Radiation dosimetry of 64Cu-PSMA-Q PET/CT imaging was performed using OLINDA/EXM 2.1 (adult male model) in 9 patients. Results:Primary lesions were detected in 21 patients. 64Cu-PSMA-Q PET/CT demonstrated a detection rate of 95.2%(20/21) for primary lesions, which was significantly higher than that of 18F-FDG PET/CT (66.7%(14/21); χ2=6.00, P=0.031). Detection rates of lymph node metastases were 65.5%(19/29) for 64Cu-PSMA-Q and 55.2%(16/29) for 18F-FDG, with no significant difference ( χ2=3.00, P=0.250). Similarly, detection rates of bone metastases were 72.4%(21/29) for 64Cu-PSMA-Q and 65.5%(19/29) for 18F-FDG respectively ( χ2=2.00, P=0.500). TBRs on 64Cu-PSMA-Q PET/CT were significantly higher than those on 18F-FDG PET/CT across primary lesions (8.3(2.2, 13.3) vs 2.3(1.0, 5.5); Z=7.16, P=0.002), regional lymph node metastases (4.9(1.4, 8.3) vs 1.7(0.9, 4.0), Z=189.34, P=0.001), and bone metastases (18.7(4.5, 26.9) vs 5.1(2.1, 9.7); Z=24.83, P=0.003). No significant difference in TBR was observed for distant lymph node metastases ( Z=1.49, P=0.135) or benign lesions ( Z=0.91, P=0.558). The whole-body effective dose of 64Cu-PSMA-Q was (28.200±1.590)μSv/MBq among the 9 patients analyzed, with no adverse events related to the tracer observed. Conclusion:64Cu-PSMA-Q is a promising novel PET imaging agent with potential clinical utility for diagnosing prostate cancer and supporting clinical decision-making.

Hepatic stellate cell(HSC)activation is a key link in the development of liver fibrosis.The metabolic reprogramming of activated HSC has become a hot topic in current research,especially the change of glycolysis is an important factor in regulating HSC activation.Based on the metabolic reprogramming in the process of HSC activation,this paper expounds the mechanism of regulating HSC activation and liver fibrosis through glycolysis,and reviews the research progress of traditional Chinese medicine and its active ingredients in regulating HSC glycolysis to prevent and treat liver fibrosis.Liver fibrosis is a complex pathological process involving multiple factors and pathways.From the perspective of regulating the glycolysis of activated HSC,it can provide a new idea for the development of anti-liver fibrosis drugs.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Purpose To investigate whether ketogenic diet(KD)can promote cognition by regulating brain metabolism and neuroinflammation in Alzheimer's disease model mice.Materials and Methods Twenty male APP/PS1 mice were randomly assigned to either a KD group(APP/PS1+KD)or a regular diet group(APP/PS1),with 10 mice in each group.Additionally,10 wild-type C57BL/6 male mice served as the control group.The APP/PS1+KD group was fed with a ketogenic feed,the APP/PS1 group received a regular diet,and the control group was maintained on standard chow for a duration of 4 months.Blood ketone levels of mice were monitored after 4 weeks and 4 months of continuous feeding.Cognitive function was assessed via the morris water maze.18F-FDG and 18F-DPA-714 micro PET/CT were performed to evaluate the effects of KD on glucose metabolism and neuroinflammation across various brain regions in the Alzheimer's disease mice.Following PET/CT imaging,brain tissue samples were collected,and the hippocampal Cal region was selected for paraffin sectioning to detect the expression of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 through immunofluorescence analysis.Results In the Morris water maze in the fourth month,compared with the control group,the APP/PS1 group had a significantly longer escape latency on days 3-4(P＜0.05 or P＜0.01).Compared with the control group,the APP/PS1 group showed a significant decrease in relative 18F-FDG uptake in brain regions such as the striatum,hippocampus,dorsal thalamus,central gray matter,superior colliculus,olfactory bulb,and midbrain(P＜0.01,P＜0.05).Compared with the APP/PS1 group,the APP/PS1+KD group showed a significant increase in relative 18F-FDG uptake in the hippocampus and dorsal thalamus(P＜0.01).Compared with the control group,the APP/PS1 group showed a significant increase in relative uptake of 18F-DPA-714 in brain regions such as the striatum,hippocampus and hypothalamus(P＜0.05 or P＜0.001).Compared with the APP/PS1 group,the APP/PS1+KD group decreased the relative uptake of 18F-DPA-714 in the hippocampus(P＜0.01).Compared with the control group and APP/PS1+KD group,the fluorescence intensity of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 protein in the brain(hippocampus)of APP/PS1 group mice was significantly increased(both P＜0.01).Conclusion KD has the potential to ameliorate cognitive and behavioral deficits in APP/PS1 mice by enhancing brain metabolism and attenuating neuroinflammation.