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.

ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

AIM:To observe the clinical efficacy of intravitreal injection of conbercept in the treatment of macular edema secondary to non-ischemic retinal vein occlusion(RVO).METHODS: Single center retrospective study. ME patients secondary to non-ischemic RVO admitted to the hospital from January 2023 to March 2024 were selected, and were divided into central retinal vein occlusion(CRVO)group and branch retinal vein occlusion(BRVO)group according to the location of obstruction. All patients were treated with intravitreal injection of conbercept once a month for 3 mo. The best corrected visual acuity(BCVA), macular foveal thickness(CMT), superficial capillary density(SVD), deep capillary density(DVD), and foveal avascular zone(FAZ)area were recorded before and after treatment(with 3 injections per course)at 1, 3, and 6 mo.RESULTS:This study included a total of 120 ME secondary to non-ischemic RVO patients(128 eyes), who were divided into CRVO group(51 cases, 56 eyes, 31 males, 20 females, mean age 61.39±10.32 y)and BRVO group(69 cases, 72 eyes, 41 males, 28 females, mean age 61.48±10.41 y)based on the location of obstruction. There was no significant difference in general data between the two groups before treatment(both P>0.05). After 1, 3, and 6 mo of treatment, both groups showed improvement in BCVA, CMT, SVD, and DVD compared to before treatment(all P<0.05). BCVA in the BRVO group was better than that in the CRVO group at all time points after treatment(all P<0.05), while there was no difference in CMT, SVD, and DVD between the two groups(all P>0.05); There was no significant difference in FAZ area between the two groups before and after treatment(both P>0.05). Follow up for 6 mo showed no significant difference in the incidence of complications between the two groups of patients(both P>0.05), but there was a significant difference in the recurrence rate(P<0.05).CONCLUSION: The first intravitreal injection of conbercept is effective in treating macular edema caused by non-ischemic CRVO and BRVO, improving visual function, reducing macular edema, and repairing retinal structure and blood flow perfusion. Notably, the recovery of visual function and improvement of capillary density are more significant in BRVO patients.

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.

ObjectiveTo investigate whether there exists an independent association beyond shared risk factors between colorectal space-occupying lesions and metabolic associated fatty liver disease （MAFLD）， and to provide new ideas for early identification of colorectal space-occupying lesions in the MAFLD population. MethodsA retrospective analysis was performed for 12 252 patients who were hospitalized in The First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） and underwent both colonoscopy and abdominal imaging （abdominal ultrasound， magnetic resonance imaging， or computed tomography） from September 1， 2018 to August 31， 2023. According to colonoscopy findings， the patients were divided into colorectal space-occupying lesion group with 6 545 patients and non-colorectal space-occupying lesion group with 5 707 patients. Baseline data were compared between the two groups. The univariate and multivariate Logistic regression analyses were used to identify influencing factors for colorectal space-occupying lesions， and further analysis was performed to investigate the association of MAFLD and liver fibrosis （assessed by fibrosis-4 ［FIB-4］， nonalcoholic fatty liver disease fibrosis score ［NFS］， and aspartate aminotransferase-to-platelet ratio index） with colorectal space-occupying lesions. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThe univariate analysis showed that compared with the non-colorectal space-occupying lesion group， the colorectal space-occupying lesion group had significantly higher age （Z=-95.628， P<0.001）， proportion of male patients （χ²=406.910， P<0.001）， body weight （Z=-24.928， P<0.001）， body mass index （BMI） （Z=-21.367， P<0.001）， diastolic blood pressure （Z=-15.527， P<0.001）， systolic blood pressure （Z=-16.965， P<0.001）， proportion of patients with history of coronary heart disease （χ²=28.112， P<0.001）/hypertension （χ²=152.993， P<0.001）/diabetes （χ²=52.175， P<0.001）/cerebral infarction （χ²=14.097， P<0.001）， white blood cell count （WBC） （Z=-12.801， P<0.001）， hemoglobin （HGB） （Z=-19.258， P<0.001）， aspartate aminotransferase （Z=-6.673， P=0.001）， alanine aminotransferase （Z=-10.375， P<0.001）， alkaline phosphatase （Z=-10.496， P<0.001）， gamma-glutamyl transpeptidase （GGT） （Z=-18.893， P<0.001）， blood urea nitrogen （Z=-13.291， P<0.001）， creatinine （Z=-16.798， P<0.001）， uric acid （Z=-16.822， P<0.001）， triglyceride （Z=-10.186， P<0.001）， and fasting blood glucose （Z=-15.761， P<0.001）. The multivariate Logistic regression analysis showed that age （odds ratio ［OR］=1.052， 95% confidence interval ［CI］： 1.045 — 1.057， P<0.001）， sex （OR=0.523， 95%CI： 0.466 — 0.587， P<0.001）， BMI （OR=1.031， 95%CI： 1.018 — 1.046， P<0.001）， history of hypertension （OR=1.140， 95%CI： 1.019 — 1.276， P=0.022）， WBC （OR=1.057， 95%CI： 1.028 — 1.087， P<0.001）， GGT （OR=1.001， 95%CI： 1.000 — 1.002， P=0.021）， Alb （OR=0.982， 95%CI： 0.969 — 0.995， P=0.008）， and HGB （OR=1.004， 95%CI： 1.001 — 1.008， P=0.019） were independent influencing factors for colorectal space-occupying lesions. In the MAFLD population， after adjustment for age， sex， BMI， history of hypertension， WBC， HGB， GGT， and Alb， intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 and NFS was still an influencing factor for colorectal space-occupying lesions （FIB-4： OR=1.457， 95%CI： 1.176 — 1.810， P<0.05； NFS： OR=1.499， 95%CI： 1.244 — 1.809， P<0.05）. Liver fibrosis degree based on FIB-4 was not significantly associated with the pathological type， location， size， or number of colorectal space-occupying lesions （all P>0.05）. While intermediate-to-high risk of advanced liver fibrosis based on NFS was not associated with pathological type， location， or size， it might be associated with the number of lesions （χ²=9.770， P<0.05）. ConclusionAge， sex， BMI， history of hypertension， WBC， HGB， GGT， and Alb are independent influencing factors for colorectal space-occupying lesions. Intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 or NFS is independently associated with colorectal space-occupying lesions， and liver fibrosis assessed by NFS might be associated with the increase in the number of lesions.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Renal interstitial fibrosis （RIF） is a common pathological change process from the development of various chronic nephropathies to the end stage， and it is an important histological manifestation of renal function decline. At present， no effective anti-fibrosis drugs have been found in clinical practice. In recent years， with the continuous development of traditional Chinese medicine （TCM） pharmacology， molecular biology， system biology， and network pharmacology， the research on regulating RIF with TCM monomer， single TCM， TCM compound， Chinese patent medicine， and TCM injection is deepening. Among them， Jianpi Yishen recipe， Shendi Bushen capsules， Jianzhong Bushen Xiaozheng decoction， Liuwei Dihuangtang， and Lycium barbarum polysaccharides can regulate transforming growth factor-β/small mother against decapentaplegic （TGF-β₁/Smads）， Wnt/β-catenin， and neurogenic locus notch homolog protein （Notch） signaling pathways. Wulingsan， Zhenwutang， pachymic acid ZA， pachymic acid ZC， and pachymic acid ZD， which mainly induce diuresis， can regulate the Wnt/β-catenin signaling pathway. Hirudin， curcumin， and Fuzheng Huayu recipe， which mainly promote blood circulation， can inhibit inflammation-related pathways such as p-nuclear transcription factor-κB （NF-κB）， Toll-like receptor 4/p-nuclear transcription factor-κB （TLR4/NF-κB）， and Janus kinase 2/signal transducer and activator of transcription 3 （JAK/STAT）， so as to achieve anti-inflammatory and anti-oxidation effects and alleviate the progression of RIF. Shenshuai Xiezhuo decoction， Shenkang injection， and Shenshuai recipe， which are mainly used for invigorating Qi， removing blood stasis， and removing turbidity， can inhibit transdifferentiation of pericytes-myofibroblasts through vascular endothelial growth factor receptor （VEGFR） signaling pathway. At present， there are many studies on the regulation of the RIF signaling pathway by TCM， but there is a lack of a systematic summary. In this study， by combing the signaling pathway of TCM in the treatment of RIF， the effective target of TCM treatment is screened， and its possible mechanism is found， which provides new ideas for clinical treatment and new drug research and development.