Objective To explore the differences in therapeutic efficacy and possible mechanism of different routes of administration of fullerene nanoparticles in the treatment of radiation retinopathy.Methods Eight-week-old adult male SD rats were randomly divided into blank group(Control),irradiation group(X-Ray),irradiation+vitreous cavity administration group[X+F(IVT)],irradiation+ocular surface administration group[X+F(OS)],and irradiation+intravenous administration group[X+F(IV)],with 5 rats in each group.The blank group was not treated,the irradiation groups exposed to X-ray irradiation to establish the model,and fullerenol nanoparticles were given to the treatment groups through different routes after irradiation.At 7,14,and 28 d after modeling,body weight and fundus changes were measured to evaluate drug safety,retinal optical coherence tomography(OCT)was used to observe the change in retinal tissue structure,and electroretinography(ERG)was applied for oscillatory potentials(OPs)to evaluate visual function.CD31 immunofluorescence staining was carried out to evaluate retinal endothelial vascular status,and in vivo imaging was utilized to evaluate the accumulation of fullerenol nanoparticles in the eyes.Results The growth curves of body weight demonstrated that fullerenol nanoparticles did not affect the growth and development of rats,with no statistical difference between the treatment groups and the control group.Irradiation resulted in a significant reduction in visual function,decreased amplitudes of a-wave and b-wave,and declined OPs(P<0.01),and significantly increased thicknesses of the ganglion cell layer(GCL)and the inner nuclear layer(INL)in the retinas,as evidenced by OCT(P<0.01),along with a notably absent presence of CD31-positive cells(P<0.01).Notably,the X+F(IVT)group obtained significantly improved visual function after intravitreal administration,effectively maintained thickness of the GCL and INL,and prevention against the loss of CD31-positive cells(P<0.01).However,no such effective results were observed in the irradiated groups receiving intravenous either ocular surface administration.In vivo imaging revealed that intravitreal administration maintained high ocular accumulation of fullerene for 96 h,while ocular surface administration sustained these concentrations for only 12 h.Intravenous administration,in contrast,only led to a predominant drug distribution in vascular-rich areas,but reduced ocular accumulation.Conclusion Fullerene nanoparticles possess a therapeutic effect on radiation retinopathy,and the intravitreal administration route demonstrates better efficacy than ocular surface and intravenous administration.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

The integration of medical treatment and disease prevention(hereinafter referred to as"med-prevent integra-tion")constitutes a vital strategy for achieving universal health objectives.Party-building initiatives in university-affiliated hospi-tals present a novel approach to enhance this integration at the primary care level.This study identifies three major challenges in current practice,including insufficient conceptual integration between medical and preventive services,inadequate cross-depart-mental coordination and resource allocation,and imperfect accountability mechanisms within Party-building frameworks.From the perspective of integrated governance,we propose a comprehensive pathway where party-building facilitates the systematic conver-gence of ideological orientation,organizational structure,cultural values,and institutional mechanisms.These findings provide both theoretical framework and practical guidance for university-affiliated hospitals to deepen primary-level med-prevent integration through Party-building initiatives.

Objective:To investigate human factors underlying radiotherapy planning safety incidents and quantitatively explore their interrelationships.Methods:A total of 1 619 safety incidents recorded in the automated plan checking system developed by West China Hospital of Sichuan University were utilized. Human factors were identified and statistically analyzed using the Human Factors Analysis and Classification System (HFACS). A Bayesian network model was developed and combined with sensitivity analysis for quantitative assessment.Results:Key contributing factors included organizational processes (12.89%), inadequate supervision (11.85%), and personnel factors (13.50%). Utilizing the established HFACS Bayesian network hybrid model in conjunction with sensitivity analysis, it has been found that the most significant influences on skill‐based errors and decision errors were condition of operators and environmental factors, with corresponding indices of 0.96 and 0.76. Additionally, personnel factors had the greatest impact on routine, with an index of 3.51.Conclusions:Key contributing factors span all HFACS levels, with organizational processes, supervision, personnel, and condition of operators each playing a significant role. Upstream factors — such as organizational climate, environment factors, and personnel factors — strongly influence downstream risks. These offer actionable insights for developing targeted safety protocols.

The integrated network image printing system can realize rapid transmission and printing for image data,and significantly enhance printing efficiency,which has been a main trend in future development of printing system.In addition,the integrated network image printing system can provide more precise and efficient solution for printing tasks that need process medical imaging,professional photographs or other high-quality images.This study strengthened the process technique on the basis of image denoising and contrast with wavelet transform,which improved the existing integrated network image printing system and tested the improved system.The result indicated that this system can effectively improve image quality.This study summarized the cases of maintaining failure in the application of this system,which target was to provide references for the application of the integrated network image printing systems.

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

Objective To investigate the association between gut microbiota metabolite,trimethy-lamine-N-oxide(TMAO),and total imaging burden in diabetic patients with cerebral small vessel disease(CSVD).Methods A prospective study was conducted on 112 elderly diabetic patients with CSVD admitted in our hospital from June 2022 to May 2024.According to the total imaging burden score,they were divided into a high burden group(burden score≥2,57 cases)and a low burden group(burden score＜2,55 cases).High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry was applied to detect the plasma level of TMAO.Then based on the tertile of plasma TMAO level,the patients were also assigned into low(＜2.44 μmol/L,38 cases),median(2.44 μmol/L≤TMAO＜5.18 μmol/L,37 cases)and high TMAO(≥5.18 μmol/L,37 cases)groups.ROC curve analysis was used to assess the predictive value of plasma TMAO level for high imaging burden in diabetic patients with CSVD.Binary logistic regression analysis was employed to analyze the correlation between plasma TMAO level and high imaging burden.Results The high burden group exhibited significantly higher plasma TMAO level than the low burden group(P=0.002).The AUC value of plasma TMAO level in predicting high imaging burden was 0.669(95％CI:0.569-0.769,P=0.002).The percentage of high imaging burden was 34.2％,54.1％and 64.9％,respectively among the low,median and high TMAO groups,with significant differences among them(Chi-square=7.270,P=0.026).Binary logistic regression analysis indicated the correlation between TMAO and high imaging burden(OR=1.178,95％CI:1.019-1.364,P=0.027).Conclusion In elderly diabetic patients with CSVD,plasma TMAO level is closely associated with high imaging burden,with higher TMAO level,higher risk for high imaging burden.

The integration of medical treatment and disease prevention(hereinafter referred to as"med-prevent integra-tion")constitutes a vital strategy for achieving universal health objectives.Party-building initiatives in university-affiliated hospi-tals present a novel approach to enhance this integration at the primary care level.This study identifies three major challenges in current practice,including insufficient conceptual integration between medical and preventive services,inadequate cross-depart-mental coordination and resource allocation,and imperfect accountability mechanisms within Party-building frameworks.From the perspective of integrated governance,we propose a comprehensive pathway where party-building facilitates the systematic conver-gence of ideological orientation,organizational structure,cultural values,and institutional mechanisms.These findings provide both theoretical framework and practical guidance for university-affiliated hospitals to deepen primary-level med-prevent integration through Party-building initiatives.

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

Objective To investigate the association between gut microbiota metabolite,trimethy-lamine-N-oxide(TMAO),and total imaging burden in diabetic patients with cerebral small vessel disease(CSVD).Methods A prospective study was conducted on 112 elderly diabetic patients with CSVD admitted in our hospital from June 2022 to May 2024.According to the total imaging burden score,they were divided into a high burden group(burden score≥2,57 cases)and a low burden group(burden score＜2,55 cases).High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry was applied to detect the plasma level of TMAO.Then based on the tertile of plasma TMAO level,the patients were also assigned into low(＜2.44 μmol/L,38 cases),median(2.44 μmol/L≤TMAO＜5.18 μmol/L,37 cases)and high TMAO(≥5.18 μmol/L,37 cases)groups.ROC curve analysis was used to assess the predictive value of plasma TMAO level for high imaging burden in diabetic patients with CSVD.Binary logistic regression analysis was employed to analyze the correlation between plasma TMAO level and high imaging burden.Results The high burden group exhibited significantly higher plasma TMAO level than the low burden group(P=0.002).The AUC value of plasma TMAO level in predicting high imaging burden was 0.669(95％CI:0.569-0.769,P=0.002).The percentage of high imaging burden was 34.2％,54.1％and 64.9％,respectively among the low,median and high TMAO groups,with significant differences among them(Chi-square=7.270,P=0.026).Binary logistic regression analysis indicated the correlation between TMAO and high imaging burden(OR=1.178,95％CI:1.019-1.364,P=0.027).Conclusion In elderly diabetic patients with CSVD,plasma TMAO level is closely associated with high imaging burden,with higher TMAO level,higher risk for high imaging burden.