AIM: To evaluate the efficacy and safety of 3% diquafosol sodium eye drops in children wearing orthokeratology lenses and with dry eye disease(DED)or at risk of DED.METHODS: Randomized controlled trials. Children with DED or at risk of DED were randomly assigned in a 1:1 ratio to receive either 3% diquafosol sodium eye drops 6 times daily or a blank control at Chongqing Aier Children's Eye Hospital from November 2023 to November 2024. The primary endpoint was the change in the Dry Eye Questionnaire-5(DEQ-5)score from baseline at 12 wk. Secondary assessments included non-invasive breakup time(NIBUT), tear meniscus height, Schirmer's test, corneal fluorescein staining score, and axial length.RESULTS: A total of 80 participants(80 eyes)were enrolled(40 in each group), the average age of the participants was 11.11±1.88 years, with 43 females(54%)and 37 males(46%), and all completed the trial. After 12 wk, the DEQ-5 scores for the diquafosol sodium group and the blank control group were 1.88±2.02 and 2.88±2.79, respectively(P=0.079). The diquafosol sodium group demonstrated a significant improvement in DEQ-5 dryness symptom scores(-0.33±0.66 vs. 0.05±0.81, P=0.023)and NIBUT(6.18±3.73 vs. -1.09±4.40 s, P<0.001)at 12 wk. Additionally, the diquafosol sodium group showed no axial length elongation, in contrast to the blank control group, which exhibited elongation(0.00±0.08 vs. 0.05±0.10 mm, P=0.013). No other significant differences were found in the secondary endpoints. No adverse events occurred during the trial.CONCLUSION: Although no statistically significant improvements were noted in the overall DEQ-5 scores, the 3% diquafosol sodium eye drops significantly improved dryness symptoms and NIBUT when compared to the blank control group.

ObjectiveTo investigate the effect of Toxoplasma gondii infection on copper metabolism in the kidneys of mice. MethodsA total of 80 7-8-week-old C57BL/6 female mice were randomly divided into four groups of 20 mice in each group after one week of adaptation， including Control group， Cu group， TgCtwh6 group and Cu+TgCtwh6 group. Mice that were not infected and fed with normal diet and water were used as the Control group； Mice fed with 1 g/kg of copper chloride processing diet and 0.1% copper chloride water for 60 consecutive days were used as Cu group； Mice infected with 25-30 TgCtwh6 cysts （one of the predominant genotype Chinese 1 in China） fed with normal diet and water were used as the TgCtwh6 group； mice infected with 25-30 TgCtwh6 cysts and fed with a processed diet containing 1 g/kg of copper chloride and water with 0.1% copper chloride for 60 consecutive days were used as the Cu+TgCtwh6 group. ICP-MS was used to determine the changes in copper content in kidney tissues. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of mouse kidney tissue. The number of apoptotic cells was observed by PI staining. Western blot was used to detect the protein expression levels of glutathione peroxidase 4 （GPX4） and superoxide dismutase （SOD1， SOD2）. RT-qPCR was used to detect the mRNA expression of cuproptosis-related genes. ResultsPathological manifestations such as inflammatory cell infiltration in the Cu group and TgCtwh6 group were seen under the microscope， and the inflammatory infiltrating cells of the renal interstitial were reduced in the Cu+TgCtwh6 group， and the pathological manifestations

ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

ObjectiveTo investigate the epidemiological and clinical characteristics of psittacosis cases in Fuyang District of Hangzhou, Zhejiang Province, and to provide evidence for clinical diagnosis, treatment, and prevention and control of this disease. MethodsEpidemiological investigation data and clinical records of psittacosis cases residing in Fuyang District of Hangzhou from September 2020 to February 2025 were collected. Descriptive epidemiological methods were applied to analyze temporal-spatial-demographic distribution characteristics, exposure history, clinical manifestations, diagnosis, treatment and laboratory findings. Comprehensive analyses were further conducted incorporating environmental surveillance and case follow-up data. ResultsAmong the 16 psittacosis cases, the male-to-female ratio was 1∶1, with an incidence rate of 0.57/100 000 for both males and females. The mean age was (59.88±10.66) years old, and the highest incidence rates were in the 70‒79 years and 60‒69 years age groups, with an incidence rate of 1.41/100 000 and 1.30/100 000, respectively. Fourteen cases (87.50%) had a history of avian exposure. The predominant clinical symptoms included fever (15 cases, 93.75%), cough (11 cases, 68.75%), expectoration (9 cases, 56.25%), and fear of cold (8 cases, 50.00%). All cases showed elevated levels of C-reactive protein (CRP), and the results of chest computed tomography (CT) indicated pneumonia in every case. Neutrophil percentage was elevated in 87.50% (14/16) of cases, while lymphocyte percentage was reduced in 93.75% (15/16) of cases. The median time from onset to first medical consultation was 4.00 days, the median time from onset to confirmed diagnosis was 9.50 days, and the median time of hospitalization was 9.00 days. Compared with non-severe cases, the severe group had significantly higher neutrophil percentage, CRP levels, and longer intervals from onset to confirmed diagnosis, onset to first antibiotic administration, and duration of hospitalization. All cases recovered and were discharged, and more than 50% were treated with omadacycline following confirmed diagnosis. ConclusionMost psittacosis cases reported definitive avian exposure history in Fuyang District of Hangzhou. Early diagnosis and treatment are critical for preventing disease progression to severe stages.

This paper outlines the development of artificial intelligence （AI） and its applications in traditional Chinese medicine （TCM） research， and elucidates the roles and advantages of large language models， knowledge graphs， and natural language processing in advancing syndrome identification， prescription generation， and mechanism exploration. Using spleen-stomach diseases as an example， it demonstrates the empowering effects of AI in classical literature mining， precise clinical syndrome differentiation， efficacy and safety prediction， and intelligent education， highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration， a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed， integrating blockchain-based smart contracts， federated learning， and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases， providing feasible pathways and a technical framework for building a high-quality， trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.

Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveTo analyze the epidemiological and clinical characteristics of the 21 confirmed monkeypox cases in a district of Chengdu City, and to provide scientific guidance for the prevention and control of subsequent monkeypox epidemics. MethodsData of confirmed monkeypox cases residing in this district were collected from the Disease Control and Prevention Information System of China. A retrospective descriptive epidemiological analysis was used to analyze the demographic, distributional and behavioral characteristics of the cases. ResultsThe first confirmed case of monkeypox was reported on July 5, 2023. Up to April 30, 2025, a total of 21 confirmed cases of monkeypox have been reported. All cases were male, with a mean age of (30.9±6.2) years. The highest proportion of cases(47.62%) was in the 30‒40 years age group. The majority were men who have sex with men (MSM) population (90.48%, 19/21). The results showed that 19.05% of cases were co-infected with HIV, and 19.05% had a history of syphilis infection. Within 21 days prior to symptom onset, 19 cases (90.48%) self-reported engaging in male-to-male sexual contact, among whom 10 cases (52.63%) reported having taken protective measures, while 9 cases (47.37%) did not take safety precautions. Thirteen cases (61.90%) had no travel history to areas with reported monkeypox cases during the 21 days before symptom onset. The predominant manifestation was exanthem (100%, 21/21), followed by fever (57.14%, 12/21) and lymphadenectasis (47.62%, 10/21). Among febrile cases, 50.00% (6/12) had low-grade fever (37.3‒38.0 ℃). All cases were identified through active medical consultation. The median interval from symptom onset to the first medical visit was 3 (2, 6) days, with a maximum interval of 14 days. The median interval from symptom onset to laboratory confirmation was 7 (5, 9) days. Six cases (28.57%) had two or more visits to the hospital, with bacterial infection being the primary initial diagnosis. ConclusionMonkeypox prevention and control efforts in a district of Chengdu City should prioritize MSM population and young and middle-aged adults aged 30 to <40 years. It is recommended to establish an integrated monkeypox epidemic prevention and control network by leveraging existing HIV/AIDS prevention and control network. Concurrently, accelerating the deployment of the national intelligent infectious disease monitoring and early warning front-end software will strengthen early detection capabilities and be beneficial for the overall effectiveness of epidemic prevention and control efforts.

Complexity science and traditional Chinese medicine （TCM） share a profound intrinsic compatibility. To address the limitations of reductionist approaches in guiding the dynamically holistic theory and practice of TCM， this paper develops​ a novel research pathway under the guidance of complexity science， using the open complex giant systems （OCGS） theory as its practical framework， upholding the fundamental principles of TCM and breaking new ground of artificial intelligence （AI）. The core tasks of this pathway involve the objectification and structured diagnosis-treatment systems， and the construction of a complex， large-scale TCM model. The paper further delineates the data architecture design and reinforcement learning training pathway. Acknowledging the differences in information processing between the human brain and computers， it proposes a training strategy that minimizes manual labeling of "syndromes" and instead focuses on the training paradigm of "herb-human interaction → syndrome manifestation → dosage adjustment". Under the guidance of complexity science theory， TCM is poised for deep integration with AI technology， driving technological innovation powered by data and computational capabilities.