Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective:To explore the clinical features, histopathological morphology, and differential diagnosis of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers.Methods:From 2020 to 2021, 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers diagnosed in Fujian Cancer Hospital (2 cases) and the Second Affiliated Hospital of Fujian Medical University (2 cases) were collected. Different ancillary procedures such as HE, special stains, immunohistochemistry, and in situ hybridization techniques were used to assess the histopathological features and immunophenotypes. The clinical data were collected and literature was reviewed.Results:All 4 cases of lymphoepithelioma-like carcinoma with abnormal expression of follicular dendritic cell markers were male. They were 32, 45, 67 and 39 years old, respectively. The main clinical manifestations were bloody phlegm, abdominal pain, fatigue and anorexia. The clinical stages at diagnosis were stage Ⅳ (3 cases) and stage Ⅱ (1 case). Cases 2 and 3 had two pathological examinations at different sites, with a total of six pathological examinations. The histomorphology showed singly scattered or nests of tumor cells in a background of abundant small lymphocytes. The tumor cells were enlarged and pleomorphic, some appeared polygonal with inconspicuous cell borders, and they were arranged in a syncytial pattern. There were megakaryocytes, multinucleated tumor cells, and a few spindle-shaped cells seen. Atypical mitosis was commonly noted. By immunohistochemistry, the tumor cells were positive for CKpan(5/6), CK8/18(4/4), CAM5.2(2/5), CK-H(0/4), CK-L(3/4), EMA(4/5), CK5/6(3/6), p63(1/6), p40(1/6), E-cadherin (4/6), SSTR2(6/6), PD-L1(5/5), LCA(0/6), vimentin(5/6), CD2 (6/6), CD23(6/6), CD35(5/6), CXCL-13(4/5) and D2-40(1/5). The Ki-67 proliferative index was 60%-95%. In situ hybridization for EBER were all positive (6/6). Special stain for reticulin showed positive staining surrounding nests of tumor cells.Conclusions:The expression of follicular dendritic cell markers in lymphoepithelioma-like carcinoma is very rare, which may be related to EBV infection. Occasionally, it can overlap with follicular dendritic cell sarcoma by morphology and immunophenotype, which can lead to misdiagnosis. Only by combining clinical information, morphological characteristics and immunophenotype can an appropriate diagnosis be made.

Objective To explore the mechanism of the long non-coding RNA(lncRNA)small nucleolar RNA host gene 1(SNHG1)/microRNA(miR)-340-5p/pentraxin 3(PTX3)signaling pathway in osimertinib resistance of lung cancer.Methods The expression levels of SNHG1,miR-340-5p and PTX3 in lung cancer tissues,adjacent tissues and osimertinib-sensitive and resistant cell lines were detected by real-time fluores-cence quantitative PCR.SNHG1 was knockdown using siRNA to detect its effects on cell proliferation,apopto-sis and osimertinib sensitivity.The dual-luciferase reporter assay verified the binding relationship between SNHG1 and miR-340-5p,as well as between miR-340-5p and PTX3.Western blotting was used to analyze the expression changes of PTX3 protein.Results SNHG1 was highly expressed in lung cancer tissues and osimer-tinib-resistant cells,while the expression of miR-340-5p was downregulated.SNHG1 inhibits the function of miR-340-5p by directly binding to it and releases the negative regulation of miR-340-5p on PTX3,resulting in the high expression of PTX3 in lung cancer drug-resistant cells.Knockdown of SNHG1 can increase the apop-tosis rate of drug-resistant cells,inhibit the ability of colony formation,and enhance the sensitivity of cells to osimertinib.The miR-340-5p inhibitor upregulated the expression of PTX3 in lung cancer sensitive cells.Con-clusion SNHG1 as competitive endogenous RNA inhibition of miR-340-5p,thus raising PTX3 expression,the drug resistance of lung cancer cells,SNHG1/miR-340-5p/PTX3 shaft may provide potential targets in the treatment of lung cancer drug resistance.

Objective:To explore the effects and potential mechanisms of cell growth regulator 1 ( CGREF1) with an EF hand domain in colorectal cancer proliferation and migration. Methods:Fifty paraffin specimens of colorectal cancer tissues and corresponding paracancerous tissues were selected from January 2023 to January 2024 from the Northern Jiangsu People's Hospital Affiliated to Yangzhou University for analysis, and TCGA, GDSC, KMPLOT and STRING databases were used to explore the expression, prognosis, immune microenvironment, drug sensitivity and related signaling pathway functions of CGREF1 in colorectal cancer. Tissue and cellular expression levels of CGREF1 were analyzed by immunohistochemistry and qRT-PCR. Lentiviral-mediated CGREF1 overexpression in SW-620 cells (OE- CGREF1 vs NC groups) was functionally characterized through CCK-8 proliferation assays, colony formation tests, and scratch wound healing migration assays, with mechanistic investigation via Western blot analysis of apoptosis markers, invasion-related proteins, and RAS/RAF/ERK pathway components. In vivo tumorigenicity was assessed by subcutaneous injection of control or CGREF1-overexpressing SW620 cells in nude mice ( n=3 per group) with tumor growth monitoring. Software of GraphPad Prism 9 was used for statistical analysis of experimental data. Results:CGREF1CGREF1RASERK Studies based on databases, clinical samples and colorectal cancer cell line analyses demonstrated that CGREF1 is downregulated in colorectal cancer, where low CGREF1 expression showed positive correlation with tumor diameter and invasion depth. CGREF1 is closely related to tumor immune infiltration microenvironment and sensitivity to multiple anti-tumor drugs. Overexpression of CGREF1 promoted cell apoptosis while inhibiting cell proliferation, invasion and migration. Overexpression of CGREF1 downregulated the expression levels of RAS, ERK and P-P38/MAPK pathway proteins. CGREF1 inhibited tumor growth in vivo. Conclusion:CGREF1 can inhibit the proliferation, colony formation, and migration of CRC cells through the RAS/ERK/MAPK pathway.

Objective:To observe the imaging features of extramacular retinoschisis (EMRS) and paravascular abnormalities (PVA) in myopic patients, and preliminary analyze the differences in age, best corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), and subfoveal choroidal thickness (SFCT).Methods:A cross-sectional clinical study. A total of 60 myopia patients with EMRS who were admitted to Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from January 2023 to June 2024 were included in the study. There were 18 male cases with 18 eyes and 42 female cases with 42 eyes. Age was (37.57±17.14) years; SE was (-10.76±4.66) D; AL was (28.36±1.87) mm. According to the characteristics of ultra-wide-angle optical coherence tomography images, PVA was divided into perivascular cysts (PC), perivascular microfolds (PM) and perivascular lamellar holes (PLH). According to the splitting level, EMRS can be divided into inner layer, middle layer and outer layer. According to SE, the affected eyes were divided into low myopia group, moderate myopia group and high myopia group. The occurrence of EMRS near optic disc, supratemporal, suprasal and subnasal, as well as the clinical characteristics of patients with EMRS at different locations, levels and forms of PVA were observed. Age, BCVA, SE, AL and SFCT of EMRS patients at different locations and levels were compared by independent sample t test. χ2 test or Fisher exact probability test were used to compare the categorical variables between groups. Results:In 60 eyes, EMRS were located in supratemporal, infratemporal, supranasal, subnasal, and paratopic discs in 36, 43, 15, 13, and 14 eyes, respectively. The EMRS in the inner and outer layers were 59 (98.3%, 59/60) and 35 (58.3%, 35/60) eyes, respectively. PVA was present in 47 eyes (78.3%, 47/60). Among them, PC, PM and PLH were 45, 39 and 18 eyes, respectively. The age of those with paratopic splitting was older than those without paratopic splitting ( t=2.720). Those with temporal splitting had worse BCVA and longer AL than those without splitting ( t=2.139, 2.119). Those with subnasal splitting had worse BCVA, higher myopia, longer AL and thinner SFCT than those without splitting. The differences were statistically significant ( t=2.926, -2.640, 2.635, -3.938; P<0.05). Compared with other types of EMRS, patients with inner EMRS had younger age ( t=-2.383), better BCVA ( t=-4.825), shorter AL ( t=-4.767), lower myopia ( t=4.791), and thicker SFCT ( t=4.791); patients with full-layer EMRS were older ( t=2.419), worse BCVA ( t=3.656), longer AL ( t=2.677), higher degree of myopia ( t=-2.755), and thinner SFCT ( t=-3.283), with statistical significance ( P<0.05). There was significant difference in SFCT among patients with or without PC ( t=-2.396, P<0.05). Compared with eyes without PM and PLH, eyes with PM had worse BCVA, longer AL, higher myopia, and thinner SFCT, and the differences were statistically significant (PM: t=2.514, 3.078, -2.811, -4.205; P<0.05; PLH: t=2.514, 2.992, -2.949, -1.773; P<0.05). Conclusions:EMRS primarily occurs in the temporal side, with the highest frequency in the inner layer. Patients with inner-layer EMRS are younger, have better BCVA, shorter AL, lower myopia, and thicker SFCT, whereas patients with full-layer EMRS exhibit the opposite characteristics.

Objective:To observe and analyze the imaging features of pathologic myopic paravascular abnormalities (PVA) and macular retinoschisis (MRS) and their relationship with clinical features.Methods:A retrospective case series study. A total of 371 eyes of 224 patients with pathological myopia with PVA and/or MRS diagnosed by examination in Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University from September 2021 to December 2023 were included in the study. There were 74 eyes in 48 males and 297 eyes in 176 females. Age were 54 (49, 61) years; equivalent spherical lens (SE) was -13.375 (-18.00,-10.00) D. Axial length (AL) was 29.84 (28.27, 31.24) mm. According to the features of ultra-wide-angle sweep source optical coherence tomography, PVA morphology was divided into blood vessels and paravascular microfolds, paravascular retinal cysts, paravascular retinal splits and paravascular lamellar macular holes. MRS was divided into inner layer, outer layer and mixed layer according to splitting level, and grouped accordingly. The presence of dome-shaped macula (DSM), internal and external lamellar macular hole, and full lamellar macular hole (FTMH) were recorded. According to whether PVA combined with MRS or not, the affected eyes were divided into PVA group and PVA combined with MRS group. According to whether MRS involved the fovea, the affected eyes were divided into two groups: MRS not involved the fovea group and MRS involved the fovea group. Mann-Whitney U test was used to compare age, SE and AL among different groups. Qualitative data were compared by χ2 test. Results:In 371 eyes, there were 120 eyes in the simple PVA group; in the MRS group, there were 251 eyes, of which 208 eyes were in the PVA combined with MRS group. There were 33, 27, 3, 14, 12, 56, 28, and 7 eyes with or without retinal detachment, choroidal neovascularization, DSM, preretinal membrane, and simple superficial detachment of neuroepithelium in inner lamina, outer lamina, and FTMH, respectively. In 328 eyes with PVA, blood vessels and paravascular microfolds, paravascular retinal cysts, paravascular retinal splits and paravascular lamellar macular holes were 151, 236, 202 and 72 eyes, respectively. There were 142 eyes with single lesion (43.29%, 142/328). There were 186 eyes with 2 or more lesions (56.71%, 186/328). There were 34 eyes in the inner MRS group, 92 eyes in the outer MRS group and 125 eyes in the mixed MRS group, respectively. It involved 155 eyes in the fovea group; 96 eyes in the fovea group were not involved. There were significant differences in the number of PVA eyes between the outer MRS group, the inner MRS group and the mixed MRS group ( χ2=30.614, 28.379; P<0.001). Compared with PVA group, PVA group combined with MRS group was more likely to have two or more PVA lesions, the difference was statistically significant ( χ2=30.535, P<0.001). Compared with the inner MRS group and mixed MRS group, the age of the simple PVA group was younger, and the age of the outer MRS group was older, and the differences were statistically significant ( P<0.05). Compared with the inner MRS group and the outer MRS group, the simple PVA group had short AL, less myopia and better optimal corrected visual acuity (BCVA), while the mixed MRS group had long AL, more myopia and worse BCVA, and the differences were statistically significant ( P<0.05). Compared with the PVA group and the inner MRS group, the fovea was more involved in the outer MRS group and the mixed MRS group, and the difference was statistically significant ( χ2=3.906, 10.836; P<0.05). Those with MRS involved in fovea were older, AL was longer, myopia was more severe, and BCVA was worse ( P<0.001). DSM-associated splits were less likely to involve macula ( P<0.001). Conclusion:PVA and MRS exhibit a variety of presentations, and their imaging features correlate with clinical features.