Objective To investigate the correlation of serum leucine-rich alpha-2 glycoprotein-1(LRG1)and Thiol levels with autoimmune antibodies and renal injury in patients with systemic lupus erythematosus nephritis(SLEN).Methods 80 SLEN patients(SLEN group)and 80 simple SLE patients(non-SLEN group)admitted to the Department of Nephrology at Qingdao Eighth People's Hospital and the Department of Rheumatology and Immunology at Affiliated Hospital of Qingdao University from January 2021 to December 2023 were selected.An enzyme-linked immunosorbent assay(ELISA)was used to detect serum LRG1 levels,while a colorimetric assay was used to detect serum Thiol levels.Pearson/Spearman correlation analysis was used to investigate the correlation between serum LRG1 and Thiol levels,autoimmune antibodies,and renal function indicators in SLEN patients.The diagnostic value of serum LRG1 and Thiol levels in SLEN was analyzed using receiver characteristic curves.Results The serum LRG1(26.00±8.76 μg/ml)and Scr(98.03±49.71μmol/L)in the SLEN group were higher than those in the non-SLEN group(16.71±5.51μg/ml,73.85±33.51μmol/L),and Thiol(80.69±36.90μmol/L)was lower than those in the non-SLEN group(131.49±45.34μmol/L),the differences were statistically significant(t=8.026,3.608,7.772,all P<0.001).Pearson/Spearman correlation analysis showed that serum LRG1 in SLEN patients was positively correlated with anti-double-stranded deoxyribonucleic acid(dsDNA)antibody,anti-complement 1q(C1q)antibody,anti-Smith antibody,serum creatinine(Scr),24-hour urine protein(r=0.226～0.637,all P<0.05),and negatively correlated with estimated glomerular filtration rate(eGFR)(r=-0.633,P<0.05).Serum Thiol was negatively correlated with anti-dsDNA antibodies,anti C1q antibodies,anti-Smith antibodies,Scr and 24-hour urine protein(r=-0.612～-0.256,all P<0.05),and positively correlated with eGFR(r=0.614,P<0.05).The AUC(95%CI)of serum LRG1 combined with Thiol levels for diagnosing of SLEN was 0.907(0.851～0.947),which was higher than that of serum LRG1 and Thiol alone at 0.802(0.731～0.860)and 0.808(0.738～0.866),and the differences were statistically significant(Z=3.450,3.749,all P<0.05).Conclusion Elevated serum LRG1 levels and decreased Thiol levels in SLEN patients were closely related to positive expression of autoimmune antibodies and renal dysfunction.Combined detection of serum LRG1 and Thiols can provide reference for the diagnosis of SLEN.

Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.

OBJECTIVES: Accurate identification of risk factors for precocious puberty is essential for clinical diagnosis and management, yet the performance of natural language processing methods applied to unstructured electronic medical record (EMR) data remains to be fully evaluated. This study aims to assess the performance of a prompt engineering method for extracting individual risk factors of precocious puberty from EMRs. METHODS: Based on the capacity and role-insight-statement-personality-experiment (CRISPE) prompt framework, both simple and optimized prompts were designed to guide the large language model GLM-4-9B in extracting 10 types of risk factors for precocious puberty from 653 EMRs. Accuracy, precision, recall, and F1-score were used as evaluation metrics for the information extraction task. RESULTS: Under simple and optimized prompt conditions, the overall accuracy, precision, recall, and F1-score of the model were 84.18%, 98.09%, 81.99%, and 89.32% versus 97.15%, 98.31%, 98.16%, and 98.23%, respectively. The optimized prompts achieved more stable performance across age (<9 years vs ≥9 years) and visit-time (<2023 vs ≥2023) subgroups compared with simple prompts. The accuracy range for extracting each risk factor was 60.03%-97.24%, while with optimized prompts, the range improved to 92.19%-99.85%. The largest performance improvement occurred for "beverage intake" (60.03% vs 92.19%), and the smallest for "maternal age of menarche" (97.24% vs 99.23%). In comparing distributions among simple prompts, optimized prompts, and ground truth, statistically significant differences were observed for snack intake, beverage intake, soy milk intake, honey intake, supplement use, tonic use, sleep quality, and sleeping with the light on (all P<0.001), while exercise (P=0.966) and maternal menarche age (P=0.952) showed no significant differences. CONCLUSIONS Compared with simple prompts, optimized prompts substantially improved the extraction performance of individual risk factors for precocious puberty from EMRs, underscoring the critical role of prompt engineering in enhancing large language model performance.
Humans ; Puberty, Precocious/epidemiology* ; Risk Factors ; Electronic Health Records ; Female ; Child ; Natural Language Processing

Human NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavoenzyme expressed at high levels in multiple solid tumors, making it an attractive target for anticancer drugs. Bioactivatable drugs targeting NQO1, such as β-lapachone (β-lap), are currently in clinical trials for the treatment of cancer. β-Lap selectively kills NQO1-positive (NQO1⁺) cancer cells by inducing reactive oxygen species (ROS) via catalytic activation of NQO1. In this study, we demonstrated that cryptotanshinone (CTS), a naturally occurring compound, induces NQO1-dependent necrosis without affecting NQO1 activity. CTS selectively kills NQO1⁺ cancer cells by inducing NQO1-dependent necrosis. Interestingly, CTS directly binds to NQO1 but does not activate its catalytic activity. In addition, CTS enables activation of JNK1/2 and PARP, accumulation of iron and Ca²⁺, and depletion of ATP and NAD⁺. Furthermore, CTS selectively suppressed tumor growth in the NQO1⁺ xenograft models, which was reversed by NQO1 inhibitor and NQO1 shRNA. In conclusion, CTS induces NQO1-dependent necrosis via the JNK1/2/iron/PARP/NAD⁺/Ca²⁺ signaling pathway. This study demonstrates the non-enzymatic function of NQO1 in inducing cell death and provides new avenues for the design and development of NQO1-targeted anticancer drugs.

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OBJECTIVE To identify Bupleurum chinense pieces and its counterfeits based on the characteristic chromatogram and UPLC-Q-TOF/MS technology.METHODS Thin layer chromatography was used to identify Bupleurum chinense and its counterfeits collected from different origins and different producing areas.Then,the chemical constituents of Bupleurum chinense and its counter-feits were compared according to the established HPLC characteristic chromatogram,and the representative differential markers of Bup-leurum chinense counterfeits were further identified by UPLC-Q-TOF/MS technology.RESULTS Thin layer chromatography showed that different original Bupleurum chinense pieces had saikosaponin A and saikosaponin D,which could be distinguished according to the intensity and position of fluorescent spots.There were 14 and 16 common peaks in the specific chromatogram of Bupleurum chinense and its vinegar-processed products respectively,and 6 components were identified.The chemical components of Bupleurum chinense pieces from different producing areas were similar,and the established method could better reflect the characteristics of Bupleurum chinense.Further comparison of the specific chromatogram of Bupleurum chinense and its counterfeits showed that the composition of B.marginatum Wall.was close to that of the authentic Bupleurum chinense.,B.bicaule Helm and B.longiradiatum Turcz.had their own characteristic peaks with high response values.The content of saponins in B.marginatum var.stenophyllum was significantly high-er.A total of 69 Bupleurum compounds were identified by UPLC-Q-TOF/MS mainly triterpenoid saponins,followed by flavonoids,a few chromones,phenylpropanoids and alkynes.The results of cluster analysis showed that the interspecific differences of Bupleurum chinense were obvious,and different Bupleurum counterfeits had representative differential markers.CONCLUSION The established characteristic chromatogram and UPLC-Q-TOF/MS method can be used for the chemical identification of Bupleurum chinense and its counterfeits,which provide a basis for the comprehensive and rational development and utilization of Bupleurum resources.

Objective To explore the perceptions,diagnostic criteria and clinical management strategies of joint surgeons regarding perioperative knee extension lag in patients with total knee arthroplasty.Methods From June to July,2024,17 joint surgeons from Peking University the First Hospital and Peking University the Third Hospital were selected as research subjects using purposive and convenience sampling.Semi-structured in-terviews were conducted.The interview data were analyzed and themes were summarized using NVivo 12.0 soft-ware.Results A total of four themes and ten sub-themes emerged from the study.Theme 1 was the basics related to knee exten-sion lag,including definition,diagnosis and incidence.Theme 2 was the attitudes of joint surgeons towards knee extension lag,including clinical value and importance.Theme 3 was the impact of knee extension lag on postop-erative functional outcomes,including the impact of preoperative knee extension lag and postoperative knee ex-tension lag on functional recovery.Theme 4 was management strategies for knee extension lag,including preop-erative rehabilitation,surgical strategies and postoperative management.Conclusion The standardized diagnosis and treatment of knee extension lag are still required further research.It is rec-ommended that relevant content be added and emphasized in the training of joint surgeons and the early rehabili-tation intervention of rehabilitation practitioners to improve the diagnosis and treatment of knee extension lag and to make it a useful addition to the perioperative management of total knee arthroplasty.

Objective To investigate the correlation of serum leucine-rich alpha-2 glycoprotein-1(LRG1)and Thiol levels with autoimmune antibodies and renal injury in patients with systemic lupus erythematosus nephritis(SLEN).Methods 80 SLEN patients(SLEN group)and 80 simple SLE patients(non-SLEN group)admitted to the Department of Nephrology at Qingdao Eighth People's Hospital and the Department of Rheumatology and Immunology at Affiliated Hospital of Qingdao University from January 2021 to December 2023 were selected.An enzyme-linked immunosorbent assay(ELISA)was used to detect serum LRG1 levels,while a colorimetric assay was used to detect serum Thiol levels.Pearson/Spearman correlation analysis was used to investigate the correlation between serum LRG1 and Thiol levels,autoimmune antibodies,and renal function indicators in SLEN patients.The diagnostic value of serum LRG1 and Thiol levels in SLEN was analyzed using receiver characteristic curves.Results The serum LRG1(26.00±8.76 μg/ml)and Scr(98.03±49.71μmol/L)in the SLEN group were higher than those in the non-SLEN group(16.71±5.51μg/ml,73.85±33.51μmol/L),and Thiol(80.69±36.90μmol/L)was lower than those in the non-SLEN group(131.49±45.34μmol/L),the differences were statistically significant(t=8.026,3.608,7.772,all P<0.001).Pearson/Spearman correlation analysis showed that serum LRG1 in SLEN patients was positively correlated with anti-double-stranded deoxyribonucleic acid(dsDNA)antibody,anti-complement 1q(C1q)antibody,anti-Smith antibody,serum creatinine(Scr),24-hour urine protein(r=0.226～0.637,all P<0.05),and negatively correlated with estimated glomerular filtration rate(eGFR)(r=-0.633,P<0.05).Serum Thiol was negatively correlated with anti-dsDNA antibodies,anti C1q antibodies,anti-Smith antibodies,Scr and 24-hour urine protein(r=-0.612～-0.256,all P<0.05),and positively correlated with eGFR(r=0.614,P<0.05).The AUC(95%CI)of serum LRG1 combined with Thiol levels for diagnosing of SLEN was 0.907(0.851～0.947),which was higher than that of serum LRG1 and Thiol alone at 0.802(0.731～0.860)and 0.808(0.738～0.866),and the differences were statistically significant(Z=3.450,3.749,all P<0.05).Conclusion Elevated serum LRG1 levels and decreased Thiol levels in SLEN patients were closely related to positive expression of autoimmune antibodies and renal dysfunction.Combined detection of serum LRG1 and Thiols can provide reference for the diagnosis of SLEN.

Hemodynamic information is important for timely intervention of cardiovascular diseases and improving long-term prognosis.Based on cardiac MR(CMR),hemodynamic force(HDF)analysis could reflect the interaction between blood flow and myocardium,hence early evaluate abnormal hemodynamics and detect mild ventricular dysfunction.The method of CMR HDF and relative research progresses in cardiovascular diseases were reviewed in this article.

Objective Using network pharmacology research methods and animal pharmacology experiments,explore the mechanism of antidepressant effects of traditional Chinese medicine Citron and Bergamot.Methods Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),ETCM,Symmap,Swiss Target Prediction,and Uniprot data platforms,screen the active ingredients and corresponding gene targets of Citron and Bergamot.Obtain depression gene targets using OMIM,TTD,and Cenecards data platforms.Using Venny 2.1 online software,draw Venn diagrams of the intersection of active ingredients and gene targets.Draw network diagrams between drugs,active ingredients,targets,and diseases using Cytoscape 3.7.2 software.Construct a protein-protein interaction(PPI)network diagram using the STRING data platform for intersecting genes.Using the Metascape data platform,perform gene ontology(GO)function and Kyoto Encyclopedia of Genesand and Genomes(KEGG)pathway enrichment analysis.A rat depression model was established using chronic unpredictable mild stress(CUMS)combined with solitary care,and animal experiments were conducted to verify the BDNF/TrkB/CREB signaling pathway obtained from network pharmacology research.Results The research results of network pharmacology methods show that there are 57 antidepressant active ingredients in Citron,65 antidepressant active ingredients in Bergamot,and important active ingredients include Acetic acid,3,4,7-trimethoxycoumarin and Citric acid,etc.Through the data platform,2717 depression targets and 430 intersection targets were identified.Through PPI network analysis,key gene targets for antidepressant effects in Citron and Bergamot were identified,including TP53,Protein kinase B1,CREB-binding protein,Brain derived neurotrophic factor,etc.Through KEGG analysis,it was found that important signaling pathways include pathways in cancer,PI3K-Akt signaling pathway,Neurotrophin signaling pathway,etc.By observing the neurotrophic factor BDNF/TrkB/CREB signaling pathway in depressed rats,the results showed that the medium dose groups of Citron and Bergamot could significantly increase serum BDNF content(P<0.05),and each treatment group could improve the damage of hippocampal neurons in rats.The high and medium dose groups of Citron and Bergamot significantly increased the expression of BDNF protein in the hippocampal CA1 region(P<0.05,P<0.01).Except for the low-dose group,which showed no difference in TrkB mRNA gene expression,all other treatment groups significantly increased the mRNA gene expression levels of hippocampal BDNF,TrkB and CREB(P<0.01).The medium dose group of Citron and Bergamot increased the expression of BDNF protein in the hippocampus(P<0.01),while the medium and low dose groups significantly increased the relative expression of TrkB protein in the hippocampus(P<0.05).The medium dose group showed an increasing trend in the relative expression of CREB protein.Conclusion Traditional Chinese medicine Citron and Bergamot have therapeutic effects on depression models in rats,and the mechanism of action may be related to the BDNF/TrkB/CREB signaling pathway.