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 construct a key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury, and provide a basis for the implementation of such treatment and nursing. Methods The draft of the key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury was determined by literature review, case study, and field investigation. The indicators of the system were determined through two rounds of Delphi consultation and using the precedence chart method. According to the criteria of indicator evaluation, the reliability of expert opinions, and the opinions of the research group, the indicators were refined and evaluated. Results Twenty experts were included for two rounds of consultation via mailed inquiries, with a 100% effective response rate in both rounds. The expert authority coefficients were both 0.945, and the Kendall’s W values were 0.347 and 0.448, respectively (P < 0.05). Following the expert consultations, 1 indicator was deleted, 12 indicators were added, and 6 indicators were modified. The key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury established in this study included 4 first-level indicators, 17 second-level indicators, and 73 third-level indicators. The means of importance assignment for all indicators were > 4.00, and the coefficients of variation were < 0.25. Conclusion The key technical indicator system for in-hospital treatment and nursing of patients with nuclear radiation injury established in this study is scientifically rigorous and practically grounded. The indicators demonstrate strong professional relevance and provide important guidance for in-hospital treatment and nursing of patients with nuclear radiation injury.

OBJECTIVE To explore whether pachymic acid （Pac） regulates mitochondrial autophagy mediated by the PTEN- induced kinase 1 （PINK1）/Parkin RBR E3 ubiquitin-protein ligase （Parkin） signaling pathway to alleviate myocardial injury in coronary heart disease （CHD） rats. METHODS SD rats were divided into control （Con） group， CHD group， Pac low-dose group （Pac-L group）， Pac high-dose group （Pac-H group）， Pac-H+PINK1/Parkin signaling pathway inhibitor group （Pac-H+3-MA group）， with 10 rats in each group. Except for the Con group， CHD models were established in the remaining groups of rats. After successful modeling， the rats in each group were intraperitoneally injected with the corresponding drugs or normal saline. After continuous intervention for 4 weeks， the left ventricular ejection fraction （LVEF）， left ventricular end-diastolic volume （LVEDV）， left ventricular end-systolic volume （LVESV）， and mean arterial pressure （MAP） of the rats were detected. The levels of creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cardiac troponin I （cTnI）， and cardiac troponin T （cTnT） in the serum， as well as the levels of tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， IL-1β， reactive oxygen species （ROS）， malondialdehyde （MDA） in the myocardial tissue， and the activities of catalase （CAT） and superoxide dismutase （SOD）， as well as the expression levels of p62， cleaved caspase-3， Parkin， PINK1 proteins and the ratio of microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）/LC3Ⅰ ratio were measured. The morphology of myocardial tissue and mitochondrial autophagic vesicles were observed， and the number of mitochondrial autophagic vesicles per unit area and the rate of cardiomyocyte apoptosis were counted. RESULTS Compared with CHD group， LVEF， MAP， IL-10 levels， CAT and SOD activities， p62， Parkin， PINK1 protein expressions， LC3Ⅱ/LC3Ⅰ ratio， the numbers of mitochondrial autophagic vesicles per unit area in the Pac-L and Pac-H E-mail：hzdpft@163.com groups were increased significantly （P＜0.05）； the levels of LVEDV， LVESV， CK-MB， LDH， cTnI， cTnT， TNF-α， IL-1β， ROS and MDA， cell apoptosis rates， and protein expression of cleaved caspase-3 were all decreased significantly （P＜0.05）； and the changes in various indicators were more pronounced in the Pac-H group （P＜0.05）； both groups showed varying degree of improvement in myocardial histopathological morphology. Compared with the Pac-H group， the aforementioned indicators in rats from the Pac-H+3-MA group were all significantly reversed （P＜0.05）. CONCLUSIONS Pac may promote mitochondrial autophagy in cardiomyocytes of CHD rats by activating the PINK1/ Parkin signaling pathway， thereby reducing inflammatory responses and oxidative stress and improving myocardial injury.

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.

ObjectiveTo clarify the neuroprotective effect of black Panacis Quinquefolii Radix（PQR） and explore its active ingredients， with the aim of establishing an activity-oriented quality evaluation method. MethodsTransgenic Tg（HuC∶EGFP） zebrafish was used to establish a neuronal injury model by aluminum chloride immersion. Different doses（10， 20 mg·L^-1） of PQR and black PQR ethanol extracts were administered. The neuroprotective effects of PQR and black PQR were compared by analyzing the fluorescent area and intensity of zebrafish neurons. Based on ultra-performance liquid chromatography（UPLC）， a fingerprint profile of black PQR was established， followed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential components were screened using the criteria of variable importance in the projection（VIP） value>1 and P<0.05. The neuroprotective activity of 14 batches of black PQR was assessed， and Spearman correlation analysis was used to identify saponins related to neuroprotective activity， which were then validated. Based on the above results， active marker components were determined， and an UPLC method was established for their quantitation with clear content limits. ResultsPharmacological efficacy results showed that both PQR and black PQR at different doses could significantly improved neuronal damage in zebrafish. At a dose of 20 mg·L^-1， black PQR demonstrated superior efficacy（P<0.05）. The fingerprint similarities of 14 batches of black PQR were>0.94， with 26 common peaks identified. Through comparison with the reference standards， 8 components were confirmed， including peak 1（ginsenoside Rg₁）， peak 2（ginsenoside Re）， peak 5（ginsenoside Rb₁）， peak 9（ginsenoside Rd）， peak 16［ginsenoside 20（S）-Rg₃］， peak 17［ginsenoside 20（R）-Rg₃］， peak 18（ginsenoside Rk₁）， and peak 19（ginsenoside Rg₅）. The results of PCA and OPLS-DA indicated that there were differences in saponins among black PQR samples from different origins， and 12 differential components were screened. All 14 batches of black PQR exhibited good protective effects on zebrafish neurons， with Shaanxi-produced black PQR showing superior protective effects compared to the other three production regions. Spearman correlation analysis revealed that a total of 11 components， including ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅， showed a significant positive correlation with the neuroprotective effect in zebrafish（P<0.05）. The activity validation results indicated that ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅ were the primary components responsible for the neuroprotective effects of black PQR. Quantitative analysis showed that the content of ginsenoside 20（S）-Rg₃ in 14 batches of black PQR ranged from 0.17% to 0.52%， and the repair rate of neuronal damage ranged from 42.77% to 97.83%. ConclusionBased on the fingerprint and neuronal protective activity， the spectrum-effect related quality control model of black PQR was established， with ginsenoside 20（S）-Rg₃ as the quality control index， and the neuronal damage repair rate≥60% as the evaluation standard， the minimum limit of ginsenoside 20（S）-Rg₃ in black PQR should be≥0.20%.

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

The plant F-box protein more axillary growth 2 (MAX2) is a key factor in the signal transduction of strigolactones (SLs) and karrinkins (KARs). As the main component of the SKP1-CUL1-FBX (SCF) complex ubiquitin ligase E3, MAX2 is responsible for specifically recognizing the target proteins, suppressor of MAX2 1/SMAX1-like proteins (SMAX1/SMXLs), which would be degraded after ubiquitination. It can thereby regulate plant morphogenesis and stress responses. There exist homologous genes of MAX2 in the important grain and oil crop soybean (Glycine max). However, its role in plant defense responses has not been investigated yet. Here, GmMAX2b, a homologous gene of MAX2, was successfully cloned from stressed soybean. Bioinformatics analysis revealed that there were two MAX2 homologous genes, GmMAX2a and GmMAX2b, with a similarity of 96.2% in soybean. Their F-box regions were highly conserved. The sequence alignment and cluster analysis of plant MAX2 homologous proteins basically reflected the evolutionary relationship of plants and also suggested that soybean MAX2 might be a multifunctional protein. Expression analysis showed that plant pathogen infection and salicylic acid treatment induced the expression of GmMAX2b in soybean, which is consistent with that of MAX2 in Arabidopsis. Ectopic expression of GmMAX2b compensated for the susceptibility of Arabidopsis max2-2 mutant to pathogen, indicating that GmMAX2b positively regulated plant disease resistance. In addition, yeast two hybrid technology was used to explore the potential target proteins of GmMAX2b. The results showed that GmMAX2b interacted with SMXL6 and weakly interacted with SMXL2. In summary, GmMAX2b is a positive regulator in plant defense responses, and its expression is induced by pathogen infection and salicylic acid treatment. GmMAX2b might exert its effect through interaction with SMXL6 and SMXL2. This study expands the theoretical exploration of soybean disease resistant F-box and provides a scientific basis for future soybean disease resistant breeding.
Glycine max/metabolism* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plant Proteins/genetics* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; F-Box Proteins/genetics* ; Arabidopsis/genetics* ; Phylogeny