Myopia has become a significant eye health problem, which is thought to result from the complex interactions of genetic and environmental factors. This review focuses on two types of hereditary retinal diseases caused by mutations in photoreceptor genes, including rod-cone cell dystrophy(retinitis pigmentosa)and cone dysfunction syndromes(achromatopsia, blue cone monochromatism and Bornholm eye disease). It systematically explores the intrinsic connection between these diseases and the myopia phenotype, and elaborates on the core mechanisms by which pathogenic genes such as RPGR and OPN1LW/OPN1MW, which cause defects in ciliary structure and protein transport and interfere with the visual signal pathway, jointly induce choroidal thinning and scleral remodeling, ultimately driving the elongation of axial length and the occurrence of myopia. By tracing the association of photoreceptor gene mutations with myopia, this article provides a new perspective for in-depth understanding of the genetic mechanism of myopia and is of great significance for the development of early risk warning and targeted intervention strategies.

Lung cancer is the leading cause of cancer-related deaths worldwide， and tumor metastasis is a key factor contributing to the mortality of most lung cancer patients. Aberrant activation of epithelial-mesenchymal transition （EMT） is a major driver of lung cancer progression and metastasis. EMT is characterized by the loss of apical-basal polarity and intercellular adhesion in highly differentiated， polarized， and organized epithelial cells， which acquire motility， migratory potential， and invasive properties. During this process， cells undergo cytoskeletal remodeling and transform into a mesenchymal phenotype， accompanied by associated changes in cellular markers. The EMT process is highly complex and is tightly regulated by intricate networks involving multiple transcription factors， post-translational controls， epigenetic modifications， and non-coding RNAs. Therefore， therapies targeting the mechanisms of malignant transformation and their associated pathways in lung cancer are of significant clinical importance. In recent years， EMT has attracted increasing attention as a potential target for cancer therapy. Chinese medicine， with its characteristics of multi-target action， low side effects， and good therapeutic efficacy， has demonstrated an important role in anticancer treatment. A series of studies have investigated the role of Chinese medicine in inhibiting EMT in lung cancer. Active ingredients of Chinese medicine， including flavonoids， glycosides， phenols， terpenoids， saccharides， and alkaloids， as well as Chinese medicine compound formulas， have shown significant regulatory effects on EMT. Their mechanisms mainly involve multiple pathways， targets， and links， including signaling pathways， exosomes， microRNAs （miRNAs）， and the tumor-associated immune microenvironment. This article summarizes the mechanisms by which EMT promotes malignant tumor progression and reviews the current research on how Chinese medicine active ingredients， monomers， and compound formulas inhibit EMT and suppress lung cancer cell migration and invasion. This study is expected to provide comprehensive theoretical information for basic and translational research on lung cancer.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To establish a standardized diagnostic and treatment pathway for chronic renal failure(CRF)based on a nephrology cluster,providing a reference for the traditional Chinese medicine(TCM)diagnosis and treatment of CRF.Methods A TCM diagnostic and treatment proto-col for CRF was developed through cluster construction.A preliminary framework for the standardized diagnostic and treatment pathway of CRF was constructed through literature research.Three rounds of Delphi expert consultation were conducted among 26 experts.The experts'enthusiasm,authority,co-ordination of opinions,importance ratings,and coefficient of variation were analyzed to ultimately form the standardized diagnostic and treatment pathway for CRF.Results The active coefficients(Caj)for the first,second,and third rounds of expert consultation were 1.000,0.923,and 1.000,respectively.The expert authority coefficients(Cr)were 0.895,0.910,and 0.923,respectively.The overall Kendall's W coefficients were 0.233,0.248,and 0.293(P＜0.001).The final stand-ardized diagnostic and treatment pathway for CRF included 4 primary indicators,19 secondary indica-tors,and 77 tertiary indicators,with mean importance ratings ranging from 4.42 to 4.87 and coeffi-cients of variation ranging from 0.072 to 0.126.Conclusion The standardized diagnostic and treat-ment pathway for CRF established based on a nephrology cluster is highly scientific and reliable,with clear guidance and ease in implementation,providing good guidance for the TCM diagnosis and treat-ment of CRF.

Objective To explore the potential targets and mechanism of Gufang Granules in treating osteoporosis through network pharmacology,molecular dynamics simulations,and in vitro experiment validation.Methods The active components of Gufang Granules were obtained from the TCMSP database and literature,and their related targets were predicted using SwissTargetPrediction database.Core drug targets were selected through protein-protein interaction(PPI)network analysis and machine learning models,and the predictive performance of the models was assessed by drawing receiver operating characteristic(ROC)curves on independent validation datasets.Gene Set Enrichment Analysis(GSEA)was used to analyze the expression and pathways of core targets.Molecular dynamics(MD)simulations were applied to evaluate the structural stability and interactions of the compound-target complexes.Non-cytotoxic concentrations of Gufang Granules containing serum were determined by the CCK-8 assay.RAW264.7 cells were treated with low,medium,and high concentrations of drug containing serum,respectively.The number of osteoclasts was quantified using TRAP staining.The expression levels of relevant genes and proteins were analyzed through qRT-PCR and Western blot methods.Results A total of 251 potential active components and 1 078 related targets of Gufang Granules were identified.The high expressions of core targets SRC and TNF were mainly associated with osteoclast differentiation,MAPK signaling pathway and PI3K/Akt signaling pathway.MD simulations showed that the core active component Glabridin exhibited strong stability and interaction with the SRC and TNF target proteins.The number of TRAP positive cells in all concentration groups of Gufang Granules was significantly reduced compared to the RANKL group(P<0.01,P<0.001).The serum containing Gufang Granules significantly reduced the mRNA expression of NFATc1,CTSK,SRC and TNF-α,and also downregulated the protein expression of NFATc1,CTSK,p-SRC and TNF-α(P<0.05,P<0.01,P<0.001).Conclusion Gufang Granules may inhibit osteoclast differentiation by downregulating the expression of NFATc1,CTSK,p-SRC and TNF-α,thereby slowing the pathological progression of osteoporosis.

Objective To construct a postoperative resistance exercise program for patients with gastric cancer,and to explore its intervention effect on symptom clusters and quality of life.Methods Based on the interactive attainment theory,the resistance exercise program was constructed through literature analysis and expert meeting method,and the feasibility of the program was confirmed through pre-experiments.The patients undergoing radical gastrectomy in the Department of Gastric Surgery of a tertiary hospital in Zhejiang province were selected as the study subjects by convenience sampling method,with 36 patients from November to December 2023 as the control group and 36 patients from January to March 2024 as the experimental group,and the intervention continued for 7 days.The experimental group received a resistance exercise program on the basis of conventional rapid recovery surgical care,and the control group received routine rapid recovery surgical care.On the first day before surgery,the 3rd postoperative day,and the 7th postoperative day,the Anderson Symptom Assessment Scale-Gastrointestinal Tumor-Specific Module Scale and the Functional Assessment of Cancer Therapy-General were used for evaluation.Results During the application of the program,a case was excluded from the experimental group,and a case was excluded from the control group.Ultimately,70 patients were included.The results of generalized estimating equation showed that there was an interaction effect between the 2 groups in the surgery-related symptom cluster and the energy deficiency symptom cluster(P＜0.05).Simple effect analysis showed that on the 7th day after surgery,the scores of the surgery-related symptom cluster in the experimental group and the control group were 3(1,5)and 5(3,9)respectively,and the scores of the energy deficiency symptom cluster were 6(8,18)and 14(8,19)respectively,with statistically significant differences(P＜0.05).The quality of life scores of the experimental group and the control group were(82.06±9.89)and(73.86±13.08)respectively,with statistically significant differences(P=0.004).No adverse events occurred in either group.Conclusion The resistance exercise program is scientific,safe and feasible,which can improve the surgery-related symptoms and energy deficiency symptoms,and improve the quality of life of patients with gastric cancer after surgery.

Objective:To investigate the attention level of oral medicine residents in standardized training (referred to as residency training) to oral aesthetic information and its influencing factors.Methods:This study was a cross-sectional study, which included 262 residents undergoing standardized training at Hospital of Stomatology, Wuhan University in January 2020. Among them, there were 73 males and 189 females, with an age range of 23-33 (26±2) years. A questionnaire survey method was used, and the questionnaire included the basic characteristics of the subjects (gender, grade, major, identity, and having training experience in prosthodontic base or not) as well as their attention to oral aesthetic information (facial proportions, facial midline, smile line, facial contour, E-line, nasolabial angle, tooth shape and contour, and tooth proportions). Differences in the attention to oral aesthetic information among residents with different basic characteristics were compared, and a multivariable logistic regression was used to identify the influencing factors.Results:Among the 262 oral medicine residents, 256 (97.7%) believed that it was necessary to pay attention to oral aesthetic information. The differences in attention to facial proportions between residents of different genders and between those with and without training experience in the prosthodontic base were statistically significant (both P<0.05). The results of the multivariate logistic regression showed that male residents were less likely to pay attention to facial proportions compared with female residents ( OR=0.45, 95% CI: 0.23-0.88). Compared with residents specializing in orthodontics, non-orthodontic residents were less likely to pay attention to the E-line ( OR=0.14-0.27, 95% CI: 0.04-0.68) and nasolabial angle ( OR=0.14-0.31, 95% CI: 0.04-0.81). Residents who were graduate students with integrated four certificates were more likely to pay attention to the E-line compared with industry-based personnel ( OR=1.88, 95% CI: 1.01-3.49). Residents without training experience in the prosthodontic base were less likely to pay attention to the facial proportion ( OR=0.44, 95% CI: 0.20-0.97) and tooth shape and contour ( OR=0.33, 95% CI: 0.11-0.98) compared with those with such training experience in prosthodontic base. Conclusions:Oral medicine residents have a high level of attention to oral aesthetic information. Gender, major, identity, and having training experience in the prosthodontic base or not are factors that influence their attention to oral aesthetic information.

Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective:To compare the efficacy of Wnt3a factor and small molecule compound CHIR99021 in culturing colorectal cancer organoid, and to explore the feasibility of replacing Wnt3a with CHIR99021.Methods:The organoids were cultured using 2 culture systems containing Wnt3a or CHIR99021, based on the colorectal cancer cell line HCT116 and rectal cancer tissue from one patient (surgical specimen from the Department of Gastrointestinal Surgery, Zhongshan Hospital Affiliated to Dalian University), including Wnt3a cell organoid, CHIR99021 cell organoid, Wnt3a tissue organoid, and CHIR99021 tissue organoid. The growth of organoids was observed under the optical microscope. The pathological characteristics of organoids and the rectal cancer tissue were analyzed by hematoxylin-eosin (HE) staining and immunohistochemical (IHC) staining, which included cytokeratin(CK) 7, CK20, Ki-67, and stemness marker CD133. The expression of β-catenin (a key Wnt pathway protein) was analyzed by Western blotting (WB) method. The half maximal inhibitory concentration (IC50) values of Wnt3a and CHIR99021 cell organoids were analyzed by drug susceptible test and GraphPad Prism 9.0 software. Independent sample- t test was used for statistical analysis. Results:Under the optical microscope, the size of CHIR99021 cell organoid was relatively uniform, while the size of the Wnt3a cell organoid was uneven, compact and dense spherical structure was formed in both organoids. HE staining showed tumor features including increased nuclear-cytoplasmic ratio and obvious nuclear atypia in the Wnt3a and CHIR99021 cell organoids. The results of IHC staining showed that CK7 was negative, and CK20 and Ki-67 were positive in the Wnt3a and CHIR99021 cell organoids. The results of WB method showed that the relative expression level of β-catenin of the CHIR99021 cell organoid was higher than that of the Wnt3a cell organoid (0.89±0.09 vs. 0.26±0.04), and the difference was statistically significant ( t=13.80, P<0.001). The results of drug susceptible test demonstrated that the IC50 value of the Wnt3a and CHIR99021 cell organoid was 10.91 and 14.55 μmol/L, respectively. Further IHC staining showed that CD133 was positive in the Wnt3a and CHIR99021 cell organoids, with stronger intensity in the CHIR99021 cell organoid. The pathological characteristics of Wnt3a and CHIR99021 tissue organoid were consistent with those of the rectal cancer tissue of the patient, with all CK7 being negative and CK20 and Ki-67 being positive. Conclusions:Both Wnt3a and CHIR99021 can successfully establish colorectal cancer organoids with consistent pathological characteristics. The IC50 value of the CHIR99021 cell organoid is high, which is related to the increased stemness of organoids. The pathological characteristics of Wnt3a and CHIR99021 tissue organoid are consistent with those of the rectal cancer tissue from the patient.

Objective To analyze the predictive value of Alberta stroke program early CT score(ASPECTS),acute stroke registry and analysis of Lausanne(ASTRAL)and totaled health risks in vascular events(THRIVE)for prognosis of intravenous thrombolysis in elderly patients with acute cerebral infarction(ACI).Methods A total of 118 elderly ACI patients receiving intravenous thrombolytic therapy in Department of Emergency Medicine of Shengli Oilfield Central Hospital from January 2021 to September 2024 were prospectively recruited.According to the score of Modified Rankin scale(mRS)at 3 months after treatment,the patients were divided into good prognosis group(73 cases)and poor prognosis group(45 cases).The scores of ASPECTS,ASTRAL and THRIVE models were compared between the two groups.ROC curve was plotted to evaluate the predictive efficiency of the three models for 3-month prognosis,and the area under the curve(AUC)was calculated.Results The poor prognosis group had significantly higher ASTRAL score and THRIVE score but obviously lower ASPECTS score when compared to the good prognosis group(P＜0.01).ROC curve analysis revealed that the AUC value of ASPECTS,ASTRAL and THRIVE models for prognosis evaluation was 0.731,0.935 and 0.799,respectively(P＜0.01),with excellent goodness of fit.Conclusion All the three models can effectively predict the prognosis of elderly ACI patients at 3 months after intravenous thrombolytic therapy.