Intravitreal anti-vascular endothelial growth factor(anti-VEGF)therapy has been widely used, but the variability in its therapeutic efficacy limits individualized treatment. In recent years, the application of artificial intelligence(AI)has opened up new avenues for personalized treatment response prediction, and its core branches include machine learning(ML)and deep learning(DL). This review systematically retrieved and analyzed 41 relevant studies published up to April 2025. Comprehensive analysis reveals that AI predictive models are evolving from forecasting single endpoints(such as visual acuity or central retinal thickness)to integrating multi-dimensional endpoints(encompassing anatomical, functional, and treatment demand parameters)and generating predictive imaging outputs. In terms of technical approaches, DL models(28 studies, accounting for 68.3%)dominate this field due to their robust image interpretation capabilities, while ML models(10 studies, 24.4%)retain significant value in the analysis of structured clinical data. Cross-disease comparisons indicate that research efforts are most concentrated on age-related macular degeneration(ARMD)and diabetic macular edema(DME), with shared conceptual frameworks for model construction, yet distinct anatomical and functional indicators are prioritized for each disease. Currently, the field confronts several key challenges, including insufficient prospective clinical validation, limited model interpretability(the “black box problem”), and a scarcity of high-quality multi-center datasets. Moving forward, it is imperative to advance real-world validation and develop explainable AI techniques to expedite the clinical translation of these predictive models.

Objective To analyze the influenza-like illness (ILI) data in Ordos City from 2017 to 2023 and conduct nucleic acid detection of the virus to understand the local influenza epidemic situation, and to provide a reliable basis for influenza prevention and control in the city. Methods Real-time quantitative polymerase chain reaction (qPCR) was used to identify virus subtypes in ILI throat swab samples. Comparisons of positive rates were conducted using the chi-square test, with a significance level of α=0.05. Results From 2017 to 2023, a total of 3,283,434 outpatient and emergency visits were recorded at the Ordos City Central Hospital, including 74,159 ILI cases, with an ILI proportion of 2.26%. The majority of ILI cases (74.43%) occurred in children aged 0~14 years old. The overall positive rate of influenza virus nucleic acid detection was 10.87%, with the highest proportion being subtype A (seasonal H3) at 43.03%. The highest detection rate was observed in the 5~14 years age group, with statistically significant differences in positive rates across age groups (χ²=155.638, P<0.001). Influenza peaks occurred mainly from November to March of the following year. From January to April, three types of influenza were prevalent alternately or mixed, while from October to December, subtype A (seasonal H3) predominated. Positive rates varied significantly across months (χ²=250.923, P<0.001). The temporal trends of ILI proportions and PCR-positive rates were consistent. Conclusion Influenza in Ordos City exhibits distinct seasonal and age distribution characteristics, with alternating or mixed circulation of three virus types. Continued efforts are needed to strengthen influenza surveillance, especially the prevention and control of influenza in infants and adolescents.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

The prevalence of summer endogenous fever is closely related to the climate of summer.Based on Li Dongyuan's yin-fire theory,this article proposed that summer-heat,irregular diet,excessive consumption of cold foods,poor living habits,and summer damp-heat internal invasion damaging the spleen can all lead to the generation of yin-fire,thereby causing endogenous fever.The core pathogenesis of summer endogenous fever lies in spleen deficiency with yang collapse,which results into the blockage of qi movement and the production of yin-fire.The yin-fire persists throughout the entire course of the disease.Treatment of summer endogenous fever should focus on eliminating yin-fire,primarily by addressing the spleen via boosting qi and raising yang to restore the spleen's ascending and stomach's descending functions,thereby dispersing yin-fire.Clearing heat and resolving dampness can purge yin-fire and then the spleen qi's circulation is restored.By analyzing the pathological changes of dampness accumulation into phlegm,fire-heat damaging yin and liver stagnation with kidney deficiency,the disease progression can be predicted.Correspondingly,comprehensive therapy of resolving phlegm,nourishing yin,soothing liver,and tonifying kidney can be employed to prevent further deterioration.Based on Li Dongyuan's yin-fire theory,Shengyang Yiwei Decoction(mainly composed of Astragali Radix,Pinelliae Rhizoma,Ginseng Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Angelicae Pubescentis Radix,Saposhnikoviae Radix,Paeoniae Radix Alba,Notopterygii Rhizoma et Radix,Citri Reticulatae Pericarpium,Poria,Bupleuri Radix,Alismatis Rhizoma,Atractylodis Macrocephalae Rhizoma,and Coptidis Rhizoma)can be used as a fundamental prescription to treat summer endogenous fever caused by yin-fire,with modifications tailored to specific clinical presentations.This theoretical exploration may provide a reference for the clinical management of summer endogenous fever.

Objective To systematically search,evaluate,and summarize the evidence for risk management of breast and ovarian cancers in carriers of breast cancer susceptibility gene 1/2(BRCA1/2)mutations.Methods A systematic search was conducted in BMJ Best Practice,UpTo-Date,the National Guideline Clearinghouse(NGC),the National Institute for Health and Care Ex-cellence(NICE),the Scottish Intercollegiate Guidelines Network(SIGN),the Guidelines Interna-tional Network(GIN),the New Zealand Guidelines Group(NZGG),the Canadian Medical Associa-tion Infobase(CMA InfoBase),the Registered Nurses' Association of Ontario(RNAO),the National Comprehensive Cancer Network(NCCN),Cancer Care Ontario(CCO),the Medlive website,the American Society of Clinical Oncology(ASCO),the European Society for Medical Oncology(ESMO),the American Cancer Society(ACS),the American College of Obstetricians and Gynecologists(ACOG),the Joanna Briggs Institute(JBI),the Cochrane Library,PubMed,Web of Science,Em-base,CINAHL,ProQuest,ClinicalTrials.gov,China National Knowledge Infrastructure,Wanfang Data,VIP Database,and SinoMed for evidence related to risk management of breast and ovarian canc-ers in BRCA1/2 mutation carriers,including clinical decisions,guidelines,systematic reviews,expert consensus,and evidence summaries.The search period was from the inception of each database to September 20,2024.Results A total of 14 articles were included,comprising 1 clinical decision,8 guidelines,and 5 expert consensus documents.Based on five themes-risk assessment,risk moni-toring,risk-reducing surgery,pharmacologic prevention,and health guidance,a total of 24 pieces of evidence were summarized.Conclusion The evidence summarization process in this study is standardized,and the summarized evidence is relatively comprehensive.Healthcare professionals should comprehensively consider patients' individual characteristics,family history,personal prefer-ences,and the accessibility of healthcare resources to achieve effective prevention and control of he-reditary tumor risks.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the association of triglyceride-glucose index(TyG)with non-alcoholic fatty liver disease(NAFLD)and its diagnostic value for NAFLD in non-obese individuals.Methods We retrospectively collected the data of non-obese individuals(BMI<25 kg/m2)undergoing routine health examination at Second Affiliated Hospital of Xi'an Jiaotong University between May,2020 and December,2023,who all received abdominal ultrasound examination for NAFLD screening.The nonlinear relationship between TyG and non-obese NAFLD was explored using restricted cubic splines(RCS),and LASSO regression was used for variable screening;the correlation between TyG and NAFLD risk was analyzed using multivariate logistic regression.The diagnostic value of TyG for non-obese NAFLD was assessed using receiver-operating characteristic(ROC)curves and sensitivity analysis.Results A total of 3723 non-obese subjects were enrolled in this study,including 432(11.6%)patients with NAFLD.Compared with the healthy individuals,the patients with NAFLD had significant elevations of systolic and diastolic blood pressures,total cholesterol,triglycerides,LDL-C,blood uric acid,fasting blood glucose,and TyG index and a decreased HDL-C level(P<0.05).Multivariate logistic regression revealed that for each one-unit increase of TyG,the risk of non-obese NAFLD increased by 2.2 folds(OR=3.22,95%CI:2.53-4.12,P<0.001).Compared with a TyG index in the lowest quartile Q1,a TyG index in the Q2,Q3 and Q4 quartiles was associated with an increased risk of NAFLD by 1.52 folds(OR=2.52,95%CI:1.20-5.95),3.56 folds(OR=4.56,95%CI:2.28-10.46),and 8.66-folds(OR=9.66,95%CI:4.83-22.18),respectively.The RCS curve demonstrated a significant linear correlation between TyG index and non-obese NALFD risk(P for nonlinear=0.019).For diagnosing non-obese NALFD,TyG index had an area under ROC curve of 0.819 with a sensitivity of 78.0%and a specificity of 71.2%.Conclusion An increase of TyG index is correlated with increased risks of NAFLD in non-obese individuals and can serve as an indicator for screening early NAFLD in healthy individuals.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.