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.

Objective: To explore the causal link of cumulative ecological risk and future orientation with health risk behaviors among higher vocational college students, so as to provide reference for reducing and preventing health risk behaviors among higher vocational college students. Methods: A longitudinal follow up study was conducted on 612 students using convenience sampling from 2 vocational colleges in Hunan Province. The Cumulative Ecological Risk Scale, Future Orientation Scale, and Health Risk Behavior Scale were used during three follow up visits (T1: September 2022, T2: June 2023, T3: March 2024), and a cross lagged panel model was constructed to examine the longitudinal causal relationship of cumulative ecological risk, future orientation and health risk behaviors. Analysis of longitudinal intermediary effect between variables by Bootstrap. Results: The cumulative ecological risk scores of T1, T2 and T3 among higher vocational college students were (2.94±1.44,2.99±1.63,3.02±1.54), future orientation scores (40.49±4.71,41.51±5.72,41.06±4.35) and health risk behavior scores (3.73±2.01,3.49±2.00,3.23±2.00). The results of repeated measures ANOVA showed that the future orientation score of T2 was higher than that of T1, and the main effect of measurement time was statistically significant ( F=5.09，P＜0.01,η 2=0.02). The health risk behavior score of T1 was higher than that of T2, and the health risk behavior score of T2 was higher than that of T3, and the main effect of measurement time was statistically significant ( F=10.12，P＜0.01,η 2=0.03).The cross lagged model showed good adaptability, with χ 2/df =7.20 ( P <0.01), relative fitting indicators GFI=0.98, CFI=0.99, TLI=0.96, IFI=0.99, NFI =0.99, and absolute fitting indicator RMSEA =0.06. Among them, the T1, T2 cumulative ecological risk showed negatively predictive effects on T2, T3 future orientation ( β =-0.24, -0.47 ), and T1, T2 cumulative ecological risk positively predicted T2, T3 health risk behavior ( β =0.20, 0.24), while T1, T2 future orientation negatively predicted T2, T3 health risk behavior ( β =-0.25, -0.18) ( P ＜0.01). Bootstrap test analysis found that T2 future orientation had a longitudinal mediating effect ( β=0.04, P ＜0.01) on the T1 cumulative ecological risk and T3 health risk behavior. Conclusions The accumulation of ecological risk among higher vocational college students can positively predict health risk behaviors, while future orientation can negatively predict healthrisk behaviors. Moreover, future orientation plays a longitudinal mediating role between accumulated ecological risks and health risk behaviors.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

OBJECTIVE: To observe the effects of Tiaoshu Anshen (regulating the hinge and calming the mind) acupuncture on sleep quality and serum levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in patients with chronic insomnia. METHODS: A total of 58 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 29 cases in each group. Tiaoshu Anshen acupuncture was applied at Baihui (GV20) and bilateral Shenmen (HT7), Sanyinjiao (SP6), Benshen (GB13) in the acupuncture group, once a day, 1-day interval was taken after 6 consecutive days of treatment. Estazolam tablet was given orally before bed in the medication group, 1 mg each time. The 4-week treatment was required in both groups. Before and after treatment, the sleep quality was assessed by Pittsburgh sleep quality index (PSQI) and polysomnography (PSG), the serum levels of 5-HT and DA were detected by ELISA. RESULTS: After treatment, the item scores and total scores of PSQI were decreased compared with those before treatment in the two groups (P<0.05); in the acupuncture group, the scores of sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorders and total score of PSQI were lower than those in the medication group (P<0.05). After treatment, the total sleep time (TST) was prolonged (P<0.05), the sleep latency (SL) and wake after sleep onset (WASO) were shortened (P<0.05), the sleep efficiency (SE%), percentage of non-rapid eye movement stage 3 (N3%), percentage of rapid eye movement stage (REM%) and serum levels of 5-HT were increased (P<0.05) compared with those before treatment; the percentage of non-rapid eye movement stage 1 (N1%), percentage of non-rapid eye movement stage 2 (N2%) and serum levels of DA were decreased (P<0.05) compared with those before treatment in the two groups. After treatment, in the acupuncture group, TST was longer, while SL and WASO were shorter than those in the medication group (P<0.05), SE%, N3%, REM% and serum level of 5-HT were higher, while N1%, N2% and serum level of DA were lower than those in the medication group (P<0.05). CONCLUSION Tiaoshu Anshen acupuncture may improve the sleep quality by regulating the serum neurotransmitter levels i.e. 5-HT and DA in patients with chronic insomnia.
Humans ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Middle Aged ; Adult ; Serotonin/blood* ; Sleep Quality ; Acupuncture Points ; Dopamine/blood* ; Aged ; Neurotransmitter Agents/blood* ; Young Adult

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by various complications, and the exact etiology remains unclear. Treatments for SLE encompass hormone therapy, plasma exchange and immunoadsorption, and targeted biological therapies. Berbamine (BBM), a cellular immunopotentiator with diverse biological functions, has not been reported to have immunomodulatory and therapeutic effects on SLE. The mice were divided into control group, model group, positive control group, low, medium and high BBM groups. In control group, C57BL/6J wild mice received intraperitoneal injection of saline. In model group, MRL/lpr lupus mice were treated with intraperitoneal injection of saline. In positive control group, MRL/lpr lupus mice received intragastric administration of hydroxychloroquine sulfate tablets [Plaquenil, 150 mg/(kg·d)]. In BBM groups, MRL/lpr lupus mice received intragastric administration of different concentration of BBM respectively [20 mg/(kg·d), 50 mg/(kg·d), 100 mg/(kg·d)]. After 8 weeks of treatment, blood was collected from the retro-orbital venous plexus, and ELISA was used to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, antinuclear antibodies (ANA), and anti-small nuclear ribonucleoprotein/Sm (snRNP/Sm) antibodies. Spleen tissues were collected for analysis of Th1/Th2 ratio by flow cytometry. The RNA and protein of spleen were extracted, and the levels of T-box transcription factor T-bet and GATA3 (GATA binding protein 3) mRNA and protein were detected by qRT-PCR and Western blot. The proliferation of white blood cells in the blood was tested by blood routine test. The histopathological changes of kidneys of each group were detected by HE staining. Compared with the model group, the levels of ANA, anti-dsDNA, and anti-snRNP/Sm antibodies were significantly reduced in the BBM-treated groups. The Th1/Th2 ratio was significantly decreased in the model group, but reversed by BBM. Compared with the control group, T-bet expression was significantly downregulated, while GATA3 expression was significantly upregulated in the model group. After BBM intervention, T-bet expression significantly increased, while GATA3 expression decreased compared with the model group. The number of white blood cells significantly decreased in the model group, and increased in the BBM-treated groups. In the model group, the glomerular mesangial and endothelial cells showed significant hyperplasia, clear thrombus was observed in the dilated capillaries, and inflammatory cells infiltrated in the renal interstitium. In medium and high BBM groups, the infiltration of inflammatory cells and capillary thrombosis were significantly decreased. In conclusion, BBM exhibits certain immunomodulatory effects on SLE and promotes the proliferation of white blood cells.
Animals ; Lupus Erythematosus, Systemic/immunology* ; Mice ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Female ; Benzylisoquinolines/pharmacology*

Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P＜0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P＜0.05).However,no significant changes were observed in absolute liver weight(P＞0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P＜0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P＜0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.