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 investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective:To investigate the G/P genotypes of group A rotavirus（RVA）in the 2023 sentinel surveillance in Jiangsu Province，and to conduct a molecular characterization analysis of the whole-genome sequences of four G9P［4］genotype RVA strains identified during surveillance.Methods:A total of 212 RVA-positive specimens collected from the surveillance system in 2023 were subjected to G/P genotyping using multiplex nested RT-PCR. Whole-genome sequencing was performed on six G9P［4］strains. The resulting complete genome sequences were preliminarily genotyped using BLAST，followed by comprehensive molecular characterization analyses utilizing BioEdit 7.0.5，MAFFT，MEGA 7.0，and iTOL software.Results:The overall RVA positivity rate was 6.22%. The predominant G/P combination in both outpatient and inpatient settings was G8P［8］. Among the six G9P［4］strains，four were successfully sequenced. All four exhibited the genotype constellation G9-P［4］-I2-R2-C2-M2-A2-N1-T2-E2-H2. While the NSP2 gene belonged to the N1 genotype，all other genes corresponded to the DS-1-like genogroup. Phylogenetically，the four Jiangsu G9P［4］strains clustered within Lineage V of the VP7 gene and formed a distinct minor subclade within the N1 branch of the NSP2 gene. Unique amino acid substitutions were identified at multiple VP7 neutralization antigenic epitope sites when compared to vaccine strains.Conclusions:The predominant circulating RVA strain in Jiangsu province during 2023 was G8P［8］. Concurrently，the relatively uncommon G9P［4］-N1 strain was detected. This strain exhibited significant amino acid differences at key epitopes compared to vaccine strains. Enhancing the proportion of whole-genome sequencing in RVA surveillance is warranted to obtain more detailed genetic information，thereby providing crucial data to support future vaccine development and optimization strategies.

Objective:To investigate the G/P genotypes of group A rotavirus（RVA）in the 2023 sentinel surveillance in Jiangsu Province，and to conduct a molecular characterization analysis of the whole-genome sequences of four G9P［4］genotype RVA strains identified during surveillance.Methods:A total of 212 RVA-positive specimens collected from the surveillance system in 2023 were subjected to G/P genotyping using multiplex nested RT-PCR. Whole-genome sequencing was performed on six G9P［4］strains. The resulting complete genome sequences were preliminarily genotyped using BLAST，followed by comprehensive molecular characterization analyses utilizing BioEdit 7.0.5，MAFFT，MEGA 7.0，and iTOL software.Results:The overall RVA positivity rate was 6.22%. The predominant G/P combination in both outpatient and inpatient settings was G8P［8］. Among the six G9P［4］strains，four were successfully sequenced. All four exhibited the genotype constellation G9-P［4］-I2-R2-C2-M2-A2-N1-T2-E2-H2. While the NSP2 gene belonged to the N1 genotype，all other genes corresponded to the DS-1-like genogroup. Phylogenetically，the four Jiangsu G9P［4］strains clustered within Lineage V of the VP7 gene and formed a distinct minor subclade within the N1 branch of the NSP2 gene. Unique amino acid substitutions were identified at multiple VP7 neutralization antigenic epitope sites when compared to vaccine strains.Conclusions:The predominant circulating RVA strain in Jiangsu province during 2023 was G8P［8］. Concurrently，the relatively uncommon G9P［4］-N1 strain was detected. This strain exhibited significant amino acid differences at key epitopes compared to vaccine strains. Enhancing the proportion of whole-genome sequencing in RVA surveillance is warranted to obtain more detailed genetic information，thereby providing crucial data to support future vaccine development and optimization strategies.

Objective:To explore the expression of CD14 in peripheral blood monocytes to predict the prognosis of patients with severe COPD complicated with pulmonary infection.Methods:A total of 122 patients with severe COPD and pulmonary infection diagnosed and treated in East Lianyungang Hospital from January 2019 to February 2022 were selected as co-infection group,127 pa-tients with severe COPD were selected as COPD group,and 62 healthy subjects in physical examination during the same period were selected as control group.After 30 days of follow-up,patients in co-infected group were divided into death group(n=16)and survival group(n=106)according to prognosis during hospitalization.Membrane CD14(mCD14)related parameters of control group,COPD group and co-infected group were compared.Dynamic changes of mCD14 related parameters were compared between death group and survival group at day 1,3,5,7 and 14 after diagnosis.Cox proportional hazard regression was used to analyze the independent risk factors of death in patients with severe COPD complicated with pulmonary infection after 30 days.Predictive values of CD14%,CD14MFI and CD14IND on prognostic death were analyzed by ROC curve,and the area under the curve(AUC)was compared.Ka-plan-Meier method was used to draw survival curve to compare the survival of patients with different CD14IND levels.Results:Com-pared with control group,CD14%,CD14MFI and CD14IND in COPD group and co-infection group were significantly decreased;com-pared with COPD group,CD14%,CD14MFI and CD14IND in co-infection group were significantly decreased,the differences were statistically significant(P<0.05).Expression of mCD14 in survival group increased steadily during the whole monitoring process,while expression in death group fluctuated at a low level.COPD grade,forced expiratory volume in 1 second/forced vital capacity(FEV1/FVC),forced expiratory volume in 1 second as a percentage of predicted value(FEV1%pred),CD14%,CD14MFI,CD14IND were all risk factors for death in patients with severe COPD complicated with pulmonary infection(P<0.05).CD14%,CD14MFI and CD14IND were negatively correlated with mortality and COPD grade in patients with severe COPD complicated with pulmonary infec-tion,while were positively correlated with FEV1%pred and FEV1/FVC(P<0.001).With CD14IND≤74.36 as cut-off value,the sensi-tivity and specificity of predicting death reached 91.22%and 95.51%respectively.The 30-day survival rate of high-risk group was 68.42%(26/38),which was significantly lower than 95.24%(80/84)of low-risk group(log-rank χ2=10.067,P=0.002).Conclusion:mCD14-related parameters are expected to be the prognostic markers of death in patients with severe COPD complicated with pulmo-nary infection,and the sensitivity and specificity of CD14IND are better than those of CD14%and CD14MFI.

Objective:To investigate the mosquito-borne viruses carried by mosquito specimens collected from Huachuan county and Huanan county in Heilongjiang province.Methods:Mosquito samples were collected locally in 2023 and processed in the laboratory. Homogenates of the mosquitoes were inoculated into cells for virus isolation, followed by molecular and bioinformatics analyses of the viral isolates.Results:In 2023, ten viral isolates were obtained from Anopheles sinensis specimens collected in Heilongjiang province, China. Among these isolates, one was identified as Culex flavivirus (CxFV), one as Menghai rhabdovirus (MRV), and eight as Nam Dinh virus (NDiV). The phylogenetic analysis showed that CxFV belongs to genotype I and is clustered with the strains isolated from Liaoning province in 2011 and Ningxia Hui autonomous Region in 2019 in the same evolutionary branch, with amino acid similarity ranging from 98.2% to 99.2% and nucleotide similarity ranging from 98.8% to 99.2%. The MRV strain belongs to the same evolutionary subclade as the strain detected in Guangdong, with both nucleotide and amino acid similarity of 98.0%. Eight NDiV isolates clustered with the South Korean isolates on the same evolutionary branch, forming an independent evolutionary sub-branch. The nucleotide similarity among these eight isolates ranged from 98.5% to 99.7%, while the amino acid similarity ranged from 98.1% to 99.7%. In comparison, when matched with other NDiV isolates from China, the nucleotide similarity of these eight isolates ranged from 94.1% to 97.8%, and the amino acid similarity ranged from 93.5% to 97.7%.Conclusions:This study represents the first isolation of CxFV, MRV, and NDiV in Heilongjiang province, China, and the findings provide fundamental data for the prevention and control of mosquito-borne viral diseases in this region.

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction