The sirtuin 1(SIRT1)is an important NAD+-dependent deacetylase that has attracted much attention in ophthalmic research in recent years. This is because the expression of SIRT1 in ocular tissues and its function are inextricably linked to the pathogenesis and progression of many ocular diseases, including dry eye, glaucoma, cataract and diabetic retinopathy. Through in-depth investigations, we have found that SIRT1, as a key regulatory protein, has a profound impact on the pathophysiological processes of ocular diseases through a variety of mechanisms, such as regulating apoptotic programs, modulating oxidative stress, mediating inflammatory responses and maintaining normal mitochondrial function. These findings indicate that SIRT1 plays an important protective role in ocular diseases. The aim of this article is to comprehensively review the latest research findings on SIRT1 in ophthalmic diseases in recent years, and hopes to provide new ideas and methods for the prevention and treatment of ophthalmic diseases by thoroughly analyzing the mechanism of action of SIRT1.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

C-C motif chemokine ligand 2 (CCL2) and its receptor CCR2 are closely related to tumorigenesis and tumor progression. The CCL2/CCR2 signaling axis promotes tumor progression through multiple mechanisms: CCL2 binds to CCR2 on the surface of tumor cells, and thus promotes tumor growth/survival and metastasis; more importantly, CCL2 recruits a variety of immunosuppressive cells to aggregate in the tumor microenvironment, and inhibits the function and activity of immune cells, promoting tumor progression. The article reviews the CCL2/CCR2 signaling axis and its role in tumors and tumor microenvironment, with particular focus on the advances in clinical research on drugs targeting CCL2/CCR2 signaling axis, in order to gain an in-depth and overall understanding of the mechanism of action of CCL2/CCR2 axis in tumor progression and develop more effective anti-tumor immunotherapeutic agents.

China has entered a stage of deep aging. The expanding aging population and subsequently an aging labor force pose significant challenges to China’s social and economic development. European Union (EU) countries have entered the aging phase earlier and to a greater extent. To address the labor shortage and the rising dependency ratio, the EU has implemented a series of policies and measures, including raising retirement age, promoting flexible retirement, enhancing work flexibility, improving welfare for elderly workers, creating age-friendly environments, focusing on occupational health, strengthening knowledge and skills training, and leveraging digital technologies in the workplace. These measures aim to prevent premature exit of elderly workers, better balance their work and life needs, improve occupational health and skills, and enhance overall work efficiency of companies. This review discussed the experience and lessons learned from the EU countries in addressing the aging workforce from the perspectives of occupational health and occupational skills development, aiming to provide rational suggestions to assist China in better adapting the challenges of aging workforce after steadily and orderly advancing the gradual reform of the statutory retirement age, thereby improving the efficiency of the overall workforce and the stability of the labor market, driving the talent dividend of highly educated and skilled middle-aged and elderly employees, and ultimately promoting sustained economic and social development.

Objective:To investigate the pharmacological basis and mechanism of Anti-cancer Essence Formula in the treatment of gastric cancer based on network pharmacology,and to provide bioinformatics basis for the clinical treatment of gastric cancer with traditional Chinese medicine.Methods:The active ingredients of Anti-cancer Essence Formula were searched in TCMSP database,and the targets of the active ingredients were further obtained using UniProt database.The targets of gastric cancer were obtained using GeneCards,OMIM and TTD databases.Cytoscape 3.9.1 software was used to build the"Disease-Component-Target"network.String database and Cytoscape 3.9.1 software were used to construct the PPI network.The transcript levels of the core genes were analyzed by UALCAN database,and the relationship between core gene expression and patient survival was analyzed by Kaplan-Meier plotter.GO function and KEGG pathway enrichment analyses were performed by DAVID database.Results:There were 236 active ingredients of Anti-Cancer Essence Formula,and 16 key targets were screened by PPI network.MAPK3,MAPK1,RELA,AKT1,TP53,FOS,MAPK14,RXRA,MAPK8 and EGFR were abnormally expressed in gastric cancer tissues(P＜0.05),and all of them showed correlation with the prognosis of gastric cancer patients(P＜0.05).GO analysis was mainly enriched in cell division,cell proliferation and apoptosis,and KEGG analysis was mainly enriched in cancer pathway,MAPK signaling pathway,Relaxin signaling pathway,TNF signaling pathway,T-cell receptor signaling pathway,Prolactin signaling pathway,and PI3K-Akt signaling pathway.Conclusion:Anti-cancer Essence Formula is characterized by the synergistic effect of multi-components,multi-targets,and multi-pathways.It mainly acts on the targets of MAPK3,MAPK1,RELA,AKT1,TP53,FOS,MAPK14,RXRA,MAPK8,and EGFR through the active ingredients such as quercetin,kaempferol,β-sitosterol,and racemic carvacrol.It also regulates the signaling pathways of MAPK,Relaxin,TNF,T-cell receptor,Prolactin,and PI3K-Akt.

Objective To investigate the impact of statistical uncertainty per control point(SUpCP)on dose calculation on volumetric modulated arc therapy(VMAT)for rectum cancer,and to analyze the accuracy and efficiency of calculation.Methods 19 patients with rectum cancer undergoing radiotherapy were selected.The initial VMAT plans were generated on Monaco TPS using SUpCP=3,then changed SUpCP in the dose calculation process as follow:10 SUpCPs(1～10)for each patient,and totally190 VMAT dose distributions were obtained.For plan evaluation,Dmax,Dmean,D95%,V50,homogeneity index(HI),conformity index(CI)of the planning target volume(PTV),dissymmetric variations of bladder,small intestine and femoral head,and time calculation(Time)were analyzed.Patient specific quality assurance(PSQA),dose deviation of isocenter(ΔDISO)and passing rate of three-dimensional dose distribution(γ33,γ32,γ22)between calculated and delivered radiation doses were measured.Results AsSUpC increased,Dmax and HI of PTV,Dmax of bladder were increased,but D95%and V50 of PTV,Time,γ32 and γ22 were decreased(P<0.05).Dmax and CI of PTV,Dmean of bladder,Dmax and Dmean of small intestine and femoral head,ΔDISO and γ33 showed no statistical significance(P>0.05).When ΔDISO<1%,gamma passing rate>90%for all VMAT plan.When SUpCP<6,Dmax of PTV<110%of the prescribed dose was obtained;while SUpCP>2,time for dose calculation was less than 5 min.Conclusion For VMAT plan of rectum cancer on Monaco TPS using XVMC algorithm,3%～5%of statistical uncertainty per control point for dose calculation,and 3%2 mm or 2%2 mm gamma criteria for three-dimensional dose verification is recommended.This study provides clinical application basis for precise dose calculation of VMAT plan of rectum cancer.

Objective:To improve the dosimetric accuracy of cell irradiation experiments by developing a method of accurately measuring the absorbed dose of ultra-thin solution in culture dishes under 200 kV medium-energy X-rays using EBT3 films.Methods:EBT3 film dose calibration was performed under Cyberknife 6 MV beam, and the beam quality (half-value layer) and effective energy of the 200 kV beam used in this study generated from Small Animal Radiation Research Platform through measurements and calculations were obtained to determine the EBT3 energy response correction factor. The 200 kV beam was utilized to irradiate three commonly used culture dishes filled with ultra-thin liquid placed on EBT3 films and the corrected EBT3 doses were taken as the liquid absorbed doses. The dose linearity of immersed films was also measured and analyzed. In addition, after modeling the irradiation environment, the independent Monte Carlo calculations of the liquid absorbed dose were performed by MCNP5 program. The calculation results were compared with the film measurement results to verify the accuracy of the measured doses.Results:The 200 kV beam had a half-value layer of 8.77 mm aluminum and effective energy of 57.4 keV, corresponding to an energy response correction factor of 0.889. The average liquid absorbed doses of large, medium and small culture dishes measured by EBT3 films under the specified parameters of 200 kV beam were (1.434±0.004) Gy, (1.467±0.011) Gy and (1.469±0.027) Gy after correction, respectively. The percentage errors from the corresponding Monte Carlo calculation doses were 0.07%, -0.70%, and 0.47%, respectively, where the relatively consistent results could be found. In addition, the dose linearity of immersed EBT3 films was also good, with coefficient of determination R2=0.9972. Conclusion:The method of measuring the dose of ultra-thin cell solution using EBT3 films proposed in this study is feasible, and the dose results obtained yield high accuracy under 200 kV beam.

Objective To construct a morphological brain network in patients with cerebral small vessel disease(CSVD)and predict it application for cognitive function.Methods A total of 64 eld-erly CSVD patients admitted in our hospital from January 2020 to February 2024 were retrospec-tively recruited.Cognitive function was assessed with Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Their clinical data,and results of cognitive function and multi-modal MRI scanning were collected and analyzed.3D T1-weighted imaging based on Kullback-Leibler divergence similarity was used to construct individual morphological brain net-work,and the connectome-based predictive model was employed to construct a cognitive predic-tion model.Results The network,which is significantly and positively correlated with the MMSE and MoCA scores,was mainly located in the default mode network,and could effectively predict individual MMSE and MoCA scores(r=0.795,P=4.436×10-15;r=0.794,P=4.974×10-15,P＜0.01).The connections,which were significantly negatively correlated with MMSE or MoCA scores,were mainly located between the salience/ventral attention network and other networks,and could also effectively predict individual MMSE and MoCA scores(r=0.766,P=1.679× 10-13;r=0.850,P=6.915×10-19,P＜0.01).Combined positive correlation and negative correla-tion networks,the model showed further improved predictive performance(r=0.849,P=7.603 × 10-19;r=0.888,P=1.445 × 10-22,P＜0.01).Conclusion Individual morphological brain network can effectively predict cognitive function in elderly CSVD patients,and can be used as a convenient tool for early warning of cognitive impairment related to CSVD.

Objective:To analyze changes in energy metabolism and oxylipin metabolism in macrophages after stimulation by Mycobacterium marinum ( M. marinum) using targeted metabolomics, and to provide insights into the mechanisms underlying the immune defense by macrophages against M. marinum infections. Methods:Mouse bone marrow-derived macrophages were obtained from the bilateral femurs of mice, and cultured cells were divided into two groups: the active M. marinum group and the inactivated M. marinum group. Bacterial suspensions were prepared using M. marinum clinical isolates; the active M. marinum group was treated with live M. marinum suspensions for 12 hours, while the inactivated M. marinum group with inactivated M. marinum suspensions for 12 hours. Cell morphology was observed through microscopy, and cell length was measured. Cell lysates collected from both groups were subjected to liquid chromatography-tandem mass spectrometry analysis to detect energy and oxylipin metabolites. A t-test was utilized to compare the lengths of macrophages between the two groups, while principal component analysis and orthogonal partial least squares-discriminant analysis were conducted to identify differential metabolites. Results:Under the microscope, macrophages in the active M. marinum group formed more granuloma-like cell aggregates compared with those in the inactivated M. marinum group; the macrophages were significantly thinner and longer in the inactivated M. marinum group (439.52 ± 91.67 μm) than in the active M. marinum group (289.96 ± 70.11 μm, P < 0.001). Principal component analysis and orthogonal partial least squares-discriminant analysis of energy metabolism and oxylipin metabolism in macrophages demonstrated good separation between the two groups. As for the energy metabolism, a total of 12 differential metabolites were identified, with the amino acid metabolism showing the most significant changes. Specifically, there was a significant increase in the content of L-citrulline, while the content of L-leucine and serine decreased. As for the oxylipin metabolism, 20 differential metabolites were identified, with the arachidonic acid metabolism showing the most significant changes. Conclusions:Macrophages stimulated by live M. marinum exhibited altered amino acid metabolism and arachidonic acid metabolism compared with those stimulated by inactivated M. marinum, characterized by an increase in L-citrulline content, a decrease in L-leucine and serine levels, and alterations in arachidonic acid content.

This experiment aims to screen and isolate bacteria for the domestication of macrophages and to identify their domestication effector molecules.Bacteria were isolated and purified from cow and sheep feces.The procedures included preparing fermentation supernatant and conducting ex-periments with a mouse peritoneal macrophage model.Nitric oxide(NO)levels were measured,tumor necrosis factor-alpha(TNF-α)was analyzed using ELISA,the domestication activity was e-valuated by mouse peritoneal macrophage model.The activated bacteria were subjected to 16S rRNA gene sequences identification,growth curves determination,and saturated ammonium sul-fate precipitation for NO assay and ELISA analysis of TNF-α to assess the phagocytic capability of domesticated macrophages against Staphylococcus aureus.One strain,ED-8,with immunomodula-tory polarizing properties was successfully isolated.Alignment of its 16S rRNA gene sequence showed 99.86％similarity with Streptococcus zooepidemicus,classifying it as such species.The fermentation supernatant significantly stimulated NO and TNF-a secretion in macrophages.The phagocytic capability against Staphylococcus aureus of macrophages polarized by ED-8 also en-hanced.This effect was retained after crude extraction,indicating the presence of immunomodula-tory activity.In this study,multiple animal chain streptococcus ED-8 was successfully isolated.Its secreted products were shown to induce the trained immunity of macrophages,enhancing their phagocytic activity.