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.

ObjectiveTo investigate the efficacy and safety of Babaodan Capsule （BBD） in the treatment of patients with chronic hepatitis B virus （HBV） infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized， double-blinded， placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital， Capital Medical University， from August 2020 to April 2023， and they were divided into treatment group （BBD） and control group （placebo）， with 60 patients in each group. The course of treatment was 24 weeks， and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps （assessed by ultrasound）， and the secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， blood lipid levels， and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Wilcoxon rank-sum test was used for comparison of ranked data between two groups； the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment， the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group （Z=-1.76 and -1.80， both P<0.05）， and after 24 weeks of treatment， the treatment group had a significantly higher polyp reduction rate than the control group （30.51% vs 10.91%， P<0.05）. The subgroup analysis showed that patients receiving combined antiviral therapy， male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment， the treatment group had a significantly better TCM syndrome score than the control group （Z=-2.35， P<0.05）； after treatment， compared with the control group， the treatment group had a significantly greater increase in high-density lipoprotein （Z=-1.85， P<0.05） and significantly lower levels of alanine aminotransferase （Z=-2.06， P <0.05）， aspartate aminotransferase （Z=-2.13， P<0.05）， total bilirubin （Z=-2.12， P<0.05）， and direct bilirubin （Z=-3.09， P<0.05）. No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps， improve TCM syndrome score， and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder， with a favorable safety profile， and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups （male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps.

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.

OBJECTIVE To investigate the effect and mechanism of morin on alveolar bone resorption in periodontitis mice based on the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS The mice were randomly divided into control group， model group， morin group （40 mg/kg）， SRT1720 （SIRT1 activator） group （5 mg/kg）， and morin+EX527 （SIRT1 inhibitor） group （40 mg/kg morin+7.5 mg/kg EX527）， with 18 mice in each group. Except for control group， mice in other groups were subjected to silk ligation to establish periodontitis model. After successful modeling， mice in each group were treated with corresponding medicinal solutions or normal saline intragastrically or intraperitoneally， once a day， for two consecutive weeks. After the last medication， serum levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6 and IL-10 were measured. The distance between the cementoenamel junction and alveolar bone crest was determined， and bone volume fraction and bone mineral density were calculated. Pathological changes of periodontal tissue were observed， and the number of osteoclasts was measured. mRNA expressions of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） in periodontal tissue， the levels of malondialdehyde （MDA） and superoxide dismutase （SOD） as well as protein expressions of SIRT1， PGC-1α， and Nrf2 were determined. RESULTS Compared with model group， the alveolar bone resorption and inflammatory cell infiltration in the periodontal tissues of mice were improved in morin group and SRT1720 group. The serum levels of TNF-α， IL-1β and IL-6， the distance between cementoenamel junction and alveolar bone crest， the number of osteoclasts in periodontal tissue， RANKL mRNA expression and the MDA level were decreased， shortened and reduced significantly （ P ＜0.05）； however， serum level of IL-10， bone volume fraction and bone mineral density， OPG mRNA expression in periodontal tissue， SOD level and protein expressions of SIRT1， PGC-1α and Nrf2 were increased significantly （ P ＜0.05）. Compared with morin group， the above pathological changes were significantly aggravated in the morin+EX527 group； and the levels of quantitative indicators were markedly reversed （ P ＜0.05）. CONCLUSIONS Morin may inhibit alveolar bone resorption in periodontitis mice by activating the SIRT1/PGC-1α/Nrf2 pathway to reduce inflammatory reaction and oxidative stress.

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.

OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Prunus mume is an ecologically and economically valuable plant with both medicinal and edible values. However, drought severely limits the promotion and cultivation of P. mume in the arid and semi-arid areas in northern China. In this study, we treated P. mume 'Meiren' with natural drought and then assessed photosynthetic and physiological indexes such as osmoregulatory substances, photosynthetic parameters, and antioxidant enzyme activities. Furthermore, we employed transcriptome sequencing to explore the internal regulatory mechanism of P. mume under drought stress. As the drought stress aggravated, the levels of chlorophyll a (Chla), chlorophyll b (Chlb), chlorophyll (a+b)[Chl(a+b)], and soluble protein (SP) in P. mume first elevated and then declined. The net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), maximum photochemical efficiency (Fv/Fm), effective photochemical quantum yield [Y(Ⅱ)], photochemical quenching (qP), and relative electron transport rate (ETR) all kept decreasing, while the levels of malondialdehyde, superoxide dismutase (SOD), peroxidase (POD), and osmoregulatory substances rose. Transcriptome sequencing revealed a total of 24 853 high-quality genes. Gene ontology (GO) enrichment showed that differentially expressed genes (DEGs) were the most under severe drought. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that the DEGs during the four drought periods were mainly involved in the biosynthesis of secondary metabolites, plant-pathogen interaction, plant hormone signal transduction, starch and sucrose metabolism, and mitogen-activated protein kinase signaling pathways. Furthermore, we identified 16 key genes associated with the drought tolerance of P. mume 'Meiren'. This study discovered that P. mume might up-regulate or down-regulate the expression of drought tolerance-related genes such as SUS, P5CS, LEA, SOD, POD, SOD1, TPPD, and TPPA via transcription factors like MYB, ERF, bHLH, NAC, and WRKY to promote the accumulation of osmoregulatory substances like sucrose and enhance the activities of antioxidant enzymes such as SOD and POD, thus reducing the harm of reactive oxygen species and protecting the structure and function of the membrane system under drought stress. The findings provide theoretical references for further exploration of candidate genes of P. mume in response to drought stress and breeding of drought-tolerant varieties.
Droughts ; Photosynthesis/physiology* ; Gene Expression Regulation, Plant ; Stress, Physiological/genetics* ; Prunus/genetics* ; Chlorophyll/metabolism* ; Plant Proteins/genetics*

Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Exosomes are ubiquitous in all types of body fluids, exhibiting a high degree of abundance and diversity. Given their distinctive structure and function, exosomes are involved in a range of life activities, including intercellular communication, material transport, and immune regulation. An increasing number of studies have identified exosomes as a source of diagnostic markers for diabetic retinopathy. Furthermore, exosomes represent a novel avenue for therapeutic intervention, with promising clinical applications. This paper examines the diagnostic and therapeutic mechanisms of exosomes in diabetic retinopathy, reviews the advancements in exosomes-based diagnostics and therapeutics for diabetic retinopathy, and aims to enhance the precision and efficiency of clinical diagnosis and treatment of diabetic retinopathy.