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.

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 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.

ObjectiveTo investigate the possible mechanism of Pibai Yucuo Formula （枇柏愈痤方， PYF） in treating acne from the perspective of skin barrier damage. MethodsThirty-two mice were randomly divided into blank group， model group， minocycline group， and PYF group， with 8 mice in each group. Except for the blank group， mice were induced by intradermal injection of Cutibacterium acnes （C.acnes） combined with topical application of artificial sebum to establish acne model. The blank group and model group received intragastric administration of 0.2 ml of distilled water， while the PYF group received intragastric administration of 22.75 g/（kg·d）of PYF， and the minocycline group received 0.013 g/（kg·d）of minocycline suspension， all once daily for 5 consecutive days. On day 0 and day 6 of the experiment， the body weight of mice in each group was recorded， and the absolute value of the body weight difference during the experiment was calculated. Skin conditions were assessed with multifunctional skin imaging system on the 2nd， 4th and 6th day of the experiment. Skin barrier function indicators including transepidermal water loss （TEWL）， and the water content of the stratum corneum and epidermis on day 0， 2， 4 and 6 of the experiment. Optical coherence tomography （OCT） was used to observe stratum corneum and skin thickness on the 1st， 3rd and 5th day of the experiment. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes， while ELISA was used to detect interleukin-17A （IL-17A） levels， and immunofluorescence staining was used to assess skin barrier-related proteins filaggrin （FLG） and loricrin （LOR） levels of skin lesions on day 6 of the experiment. ResultsCompared to the blank group， the model group showed a decrease in body weight on day 6， and an increase in the absolute value of the difference in body weight before and after the experiment （P＜0.05）. On day 4 and 6， TEWL values increased， while water content in the skin stratum corneum and epidermis decreased （P＜0.05）， accompanied by elevated IL-17A level and reduced immunofluorescence intensity of FLG and LOR proteins （P＜0.05）. The model group mice showed papules or pustules at the skin modeling site with progressively worsening desquamation under multifunctional skin imaging system. OCT revealed focal epidermal protrusions， blurred epidermal-dermal boundaries， and disorganized structural layers. HE staining showed significant epidermal hyperkeratosis and incomplete keratinization in the skin， with keratin plug formation in hair follicles and glandular lumens， thickened stratum corneum， hyperplasia of the stratum spinosum， as well as dense dermal inflammatory cell infiltration， and capillary dilation. Compared to the model group， both the minocycline group and the PYF group showed a reduced difference in body weight before and after experiment （P＜0.05）. On day 4 and 6， the TEWL value decreased， and water content of the skin stratum corneum increased （P＜0.05）； on day 6， the IL-17A level in the skin lesions decreased and immunofluorescence intensity of FLG and LOR proteins increased （P＜0.05）. On day 4 and 6， the severity of the skin lesions and range of redness and swelling were lighter than those in the model group， with reverted epidermal thickness， smoother surface and clearer epidermis-dermis boundary. HE staining showed that the degree of skin keratinization was reduced， and the inflammatory infiltration and vascular dilation in the dermis were improved compared to the model group. The PYF group showed better results than the minocycline group in reducing TEWL value on day 4 （P＜0.05）. ConclusionPYF may improve inflammation and skin barrier damage by downregulating IL-17A levels in lesion tissue and increasing skin barrier-related proteins， which could be one of the potential mechanism of action on acne.

Objective:To summarize the clinical symptoms of cyclic vomiting syndrome（CVS）in children and investigate its association with small intestinal bacterial overgrowth（SIBO）.Methods:A total of 89 children who were diagnosed as CVS and improved lactulose hydrogen breath test (LHBT) in the Pediatric Department of Beijing Tsinghua Changgung Hospital from June 2020 to June 2023 were selected as CVS group.Simultaneously，50 healthy children with physical examination in our hospital were selected as the control group. According to the results of LHBT,the children with CVS were divided into SIBO group (LHBT positive) and non-SIBO group (LHBT negative). The clinical data of children in each group were compared.Results:Among the 89 CVS patients，there were 42 males and 47 females，with a mean age of（7.50±3.54）years.Common accompanying symptoms included excessive sleepiness（76 cases，85.39%），anorexia(62 cases，69.66%），constipation（55 cases，61.80%），abdominal pain（34 cases,38.20%）and so on. There were no significant differences in age and gender between children in CVS group and control group ( P>0.05). The body mass index of CVS group was lower than that of control group.The positive rate of LHBT was higher than that of the control group (56.18% vs. 8.00%),the difference was statistically significant ( P<0.05),and the concentrations of hydrogen and methane in CVS group were higher than those of the control group at different time points( P<0.05).Among 89 children with CVS,there were 50 cases in SIBO group and 39 cases in non-SIBO group. There were no significant differences in gender,age and body mass index between the two groups ( P>0.05). The constipation rate and moderate/severe disease rate in SIBO group were higher than those in non-SIBO group (88.00% vs. 28.21%,94.00% vs. 43.59%),and the differences were statistically significant ( P<0.05). Conclusion:The incidence of SIBO in children with CVS is higher,and SIBO may play a key role in CVS. CVS children with SIBO have higher disease severity.

Objective To explore the influencing factors of neonatal pneumonia complicated with myocardial damage and Th1/Th2 cytokines,and construct a line chart model.Methods A total of 390 neonates with pneumonia who were treated in Mianyang People's Hospital were selected as the study subjects and randomly divided into a modeling cohort(n=273)and a validation cohort(n=117)according to a 7∶3 ratio.They were further divided into myocardial damage group and non-myocardial damage group according to whether they had concurrent myocardial damage.Enzyme linked immunosorbent assay(ELISA)was used to measure Th1/Th2 cytokines(IFN-γ,IL-6,TNF-α,IL-4,IL-2 and IL-10),and the Mindray BS-280 automatic biochemical analyzer was used to measure hs-cTn I,CK-MB,LDH and CK.Logistic regression equation was used to screen the influencing factors of neonatal pneumonia complicated with myocardial damage.R software was used to construct a line chart model,and the receiver operating characteristic curve(ROC)and area under the ROC curve(AUC)were used to analyze the predictive ability of the model.The Hosmer-Lemeshow goodness-of-fit test was used,and a calibration curve was drawn to evaluate the calibration of the model.The decision curve analysis(DCA)was used to evaluate the clinical effectiveness.Results The incidence of myocardial damage in 390 neonates with pneumonia was 28.21%.Modeling cohort and validetion cohort,the 1min Apgar score in the myocardial damage group was lower than that in the non-myocardial damage group(t=3.314,2.619),and CK-MB,LDH,CK,hs-cTnI,IL-2,IFN-γ,TNF-α,IL-6,IL-10 and IL-4 were higher than those in the non-myocardial damage group(t=5.805～18.914),and the proportions of severe pneumonia,low birthweight infant,premature infants were higher than those in the non-myocardial damage group(χ2=4.464～41.497),and the differences were statistically significant(all P<0.05),respectively.The Logistic regression equation showed that low birth weight,1-minute Apgar score,premature birth,hs-cTnI,IL-2,IFN-γ,IL-6 and IL-4 were factors affecting neonatal pneumonia complicated with myocardial damage(Wald χ2=10.330～14.328,all P<0.05).The AUC(95%CI)of the nomogram model constructed based on the factors affecting neonatal pneumonia complicated with myocardial damage was 0.880(0.839～0.921)in the modeling cohort and 0.910(0.856～0.964)in the validation cohort,with slopes of the calibration curves close to 1,and the clinical net benefit rate was the highest in the ranges of 0.1～0.8 and 0.0～0.7.Conclusion The nomogram model,which includes Th1/Th2 cytokines,hs-cTnI,1-minute Apgar score,premature infants and low-birth-weight infants has high predictive value for neonatal pneumonia complicated with myocardial damage.It can help clinicians identify high-risk populations,take reasonable diagnostic and treatment measures,and reduce the risk of myocardial damage.

BACKGROUND:Previous studies have shown that 1,8-cineole has anti-inflammatory,antioxidation,antibacterial and anti-tumor effects.It has good anti-inflammatory effects in many diseases.OBJECTIVE:To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis.METHODS:Thirty Sprague-Dawley rats were assigned into normal control group,periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method.Except for the normal control group,rats in the other groups were induced into experimental periodontitis.The periodontitis model was constructed by the orthodontic ligature wire method.Eight weeks after modeling,in the 1,8-cineole group,1,8-cineole was placed into periodontal pockets,twice per day for 4 weeks.In the normal control group and the periodontitis control group,the same amount of normal saline was placed into periodontal pockets,twice per day for 4 weeks.After administration,general observation and periodontal clinical indicators were performed.Hematoxylin-eosin staining was used for periodontal histological evaluation.The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected.RESULTS AND CONCLUSION:(1)Compared with the normal control group,rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth(P<0.05),increased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),decreased serum level of interleukin 10(P<0.05),increased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and decreased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group,periodontal inflammation was obvious in the periodontitis control group.(2)Compared with the periodontitis control group,rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth(P<0.05),decreased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),increased serum level of interleukin 10(P<0.05),decreased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and increased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group,periodontal inflammation was remarkably alleviated in the 1,8-cineole group.To conclude,1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis.

Objective To explore the method for grading the degree of uterine adhesion in a rat model.Methods A rat model of uterine adhesion was established using the double-injury method.Paraffin sections were observed using HE staining and Masson staining to compare morphological changes in the uterus,endometrial thickness,gland and vessel counts,uterine cavity area,and adhesion severity.Rat sections were classified into three grades based on uterine cavity area for comparative analysis.Results The average uterine cavity area and uterine cavity area/endometrial layer area were smaller in rats in the model group compared with the blank group(P＜0.01).The uterine cavity area/endometrial layer area ratio was categorized into grades Ⅰ,Ⅱ,and Ⅲ,with a significant difference among the grades(P＜0.05,P＜0.01).Conclusions The uterine cavity area/endometrial layer area ratio may reflect the grading difference in the degree of uterine adhesion in rats with uterine adhesions.This ratio may thus be used as a grading-evaluation criterion in the rat model of uterine adhesion,with implications for diagnostic grading in this model.