Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8(NEDD8)to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme(NAE)(E1),E2 NEDD8-conjugating enzyme(E2),and E3 NEDD8-ligase(E3).The most extensively studied substrates of neddylation are members of the cullin family,which act as scaffold components for cullin ring E3 ubiquitin ligases(CRLs).Since cullin neddylation activates CRLs,which are frequently overactive in tumors,inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies.This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions(PPIs)within the neddylation enzymatic cascade.

Objective To explore the experience of social isolation among caregivers of stroke patients,and to provide corresponding references for the development of targeted intervention strategies.Methods A descriptive qualitative study was used to select 14 caregivers of hospitalized stroke patients attending the Department of Neurology and Neurosurgery of a tertiary-level hospital in Kunming City from September to November 2023 through purposive sampling method,and the data were analyzed using traditional content analysis.Results A total of 3 themes and 10 sub-themes were extracted,including characterization of social alienation(accumulation of negative emotions,limited social contact,dissolution of self-identity),drivers of social alienation(limitations of disease perception,multiple role conflicts,lack of support resources,constraints of caregiving responsibilities),and coping needs for social alienation(craving for informational support,appeal for emotional support,and expectation of policy support).Conclusion Caregivers of stroke patients are socially alienated due to limited social contact,multiple role conflicts,and lack of support resources,etc.Healthcare professionals should conduct regular assessments,provide targeted education and training,and strengthen multidimensional support in order to help them reintegrate into society and improve the overall quality of life of stroke families.

Objective:To explore the clinical efficacy of the sixth generation CyberKnife (M6) in treating patients with brain metastases, and analyze clinical characteristics and dosimetric factors.Methods:Clinical data of patients with brain metastases who received CyberKnife treatment at Sichuan Cancer Hospital from April 2023 to March 2024 were retrospectively analyzed. All patients were treated with CyberKnife with 6 MV X-ray. According to the maximum diameter of brain metastases, the radiation prescription dose of brain metastases was adjusted. The tumor remission, recurrence, 6-month and 1-year overall survival (OS), local control (LC) of intracranial target lesions, progression-free survival (PFS), distant metastasis-free survival (DMFS) of intracranial brain metastases and adverse reactions were evaluated. According to the median biological dose, the survival difference between the groups was compared. Survival analysis was conducted by Kaplan-Meier method. Survival differences among different groups were analyzed by log-rank test.Results:A total of 63 eligible patients with brain metastases were enrolled, with a median age of 59 years (rang: 36-80 years). Among them, 47 patients were diagnosed with primary tumors originating from the lungs, 16 patients with primary tumors originating from other organs; 44 patients with single brain metastases, and 19 patients with 2-3 lesions, respectively. The median biological dose was 67.2 Gy (rang: 47.4-86.4 Gy), and the median single dose was 8 Gy/F (rang: 4-24 Gy/F). The follow-up was conducted until July 15, 2024. The median follow-up time for the entire group was 9 months (rang: 2-15 months). Among the 87 target lesions treated with CyberKnife, 11 patients corresponding to 14 target lesions experienced local recurrence. And the 6-month and 1-year LC rates were 92.5% and 70.9%, respectively. Ten patients corresponding to 16 target lesions died. And the 6-month and 1-year OS rates were 92.7% and 74.8%, respectively. Thirty-five patients corresponding to 50 target lesions experienced disease progression. And the 6-month and 1-year PFS rates were 64.3% and 25.5%, respectively. Thirty-three patients corresponding to 48 target lesions showed distant metastasis outside the target lesions, with a 6-month DMFS of 67.0% and a 1-year DMFS of 33.9%. Group comparison showed that 43 target lesions in the group receiving ≤67.2 Gy irradiation and 44 in the group receiving >67.2 Gy irradiation. The 6-month LC, OS, PFS, and DMFS rates between two groups were 89.8% vs. 97.7% ( P=0.127), 89.8% vs. 95.4% ( P=0.305), 65.4% vs. 68.5% ( P=0.514), 65.4% vs. 68.5% ( P=0.516), respectively. The 1-year LC, OS, PFS, and DMFS rates between two groups were 54.1% vs. 89.5% ( P=0.003), 67.3% vs. 82.9% ( P=0.219), 19.2% vs. 32.7% ( P=0.370) and 23.3% vs. 33.0% ( P=0.533). During the follow-up, only 2 patients (3.2%) were found to have grade 1-2 radiation-induced brain injury (asymptomatic brain injury) by MRI examination, and there were no other radiotherapy related adverse reactions. Conclusions:CyberKnife therapy is clinically effective for brain metastases, with mild adverse reactions. Increasing the tumor irradiation dose can improve local tumor control and is expected to further improve the OS of patients.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

The infection incidence rate of Candida albicans,an opportunistic pathogenic fungus,has increased each year.Currently,the increased number of patients with immunodeficiency,the limited number of antifungal drugs,and drug resistance are the main reasons for the high incidence and high mortality of C.albicans related diseases.Therefore alternative therapies for combating C.albicans infections are urgently needed.Many recent studies have suggested that probiotics might inhibit C.albicans infection both directly,through inhibiting adhesion,growth,and biofilm formation,and indirectly,through regulating the host immune response,without leading to drug resistance.Because of the multiple pathways involved in these effects,the mechanism of probiotics in combating C.albicans infection has not been fully elucidated,and systematic evaluations of this mechanism are lacking.This article provides an in-depth analysis of the mechanism of probiotics in combating C.albicans infection described in recent years,to contribute to the development of new methods to resist C.albicans infection and,more importantly,the clinical development of new therapies for the treatment of drug-resistant fungal infections.

Giant cell-rich osteosarcoma(GCRO)is a special subtype of osteosarcoma,and is rare.This paper reported the clinical and imaging data of the patient with GCRO who had special imaging manifestations,and to provide the reference for clinical diagnosis and treatment of GCRO.The patient,a 69-year-old female,was admitted to the hospital due to the discovery of a mass in the right lower leg for 1 month.The X-ray imaging manifestations showed that the cortical bones on the opposite edges of the tibia and fibula presented mild moth-eaten changes.The plain CT scan imaging manifestations showed that there was a mass within the muscle,and the cortical bones on the opposite edges of the tibia and fibula were destroyed.The tumor only involved the superficial cortical bones and did not invade the deep cortical bones and the medullary cavity.The MRI imaging manifestations showed that the local bones of the tibia and fibula adjacent to the tumor were destroyed,and the medullary cavity was not invaded.An extended resection of the mass was performed,and the postoperative pathological diagnosis was GCRO.The patient received chemotherapy after the operation.However,a tumor in the right lower leg recurred 15 months after the operation.The patient passed away 21 months after the operation.Giant cell-rich osteosarcoma often leads to misdiagnosis or missed diagnosis due to its non-specific clinical manifestations.This paper explored the clinical manifestations and imaging data of the patient with GCRO in order to improve the clinical understanding level and the level of diagnosis and treatment of the clinicians about this disease.

Objective:To investigate the feasibility of the combination of free breathing with the high-threshold, short-delay technique in reducing radiation dose and the volumes of iodinated contrast agent in coronary computed tomography angiography (CCTA) for obese patients.Methods:The data of 73 obese patients with weights > 85 kg and body mass indices (BMIs) > 30 kg/m 2 who received CCTA in the Radiology Department of the Peking University Third Hospital from February 2023 to May 2024 were prospectively collected. These patients were divided into a control group (31 patients) and an experimental group (42 patients). Data were collected from the control group and experimental groups under breath-holding and free-breathing conditions, respectively. The bolus tracking thresholds, delay times, and ICA injection durations were set at 100 HU, 7 s, and 12 s for the control group and at 250 HU, 2 s, and 8 s for the experimental group, respectively. Other scanning and reconstruction parameters of both groups were consistent. The CT values and their standard deviations ( SD) of both groups were assessed and compared, with the CT values involving the lumens of the aorta (AO) root, left anterior descending (LAD), left circumflex artery (LCX), and right coronary artery (RCA). The signal-to-noise ratios (SNR) and contrast-to-noise ratio (CNR) were also calculated. The subjective assessment of image quality was performed for the 18 coronary artery segments using a 4-point scale. The effective radiation doses ( E) and the volumes of iodinated contrast agent of both groups were recorded and compared. The statistical differences in the aforementioned parameters between the groups were tested and analyzed using the analysis of variance (ANOVA), the Mann-Whitney U test, or the χ 2 test. With the results of the ICA as the gold standard, the diagnostic performance of the combination of free-breathing with the high-threshold, short-delay technique in CCTA for obese patients was assessed. Results:There was no statistically significant difference ( P > 0.05) in coronary artery images between both groups, specifically regarding the CT, SNR, and CNR values of the lumens of the AO roots, LAD, LCX, and RCA, as well as the SD values of the AO roots. Both groups received subjective scores of ≥ 3 for coronary artery images, meeting the diagnostic criteria, with no statistically significant differences ( P > 0.05). Compared with the results of the ICA, the analyses of the coronary artery segments of 23 patients from the experimental group, revealed that the accuracy, sensitivity, and specificity of CCTA in the diagnosis of > 50% stenosis were 89%, 86%, and 97%, respectively. Compared to that (45 ml) of the control group, the volume (30 ml) of iodinated contrast agent of the experimental group decreased by 33.3%, with no statistically significant difference in the effective radiation dose ( E) between both groups ( P > 0.05). Conclusions:The combination of free breathing with the high-threshold, short-delay technique can further reduce the volume of the ICA for obese patients while maintaining high CCTA image quality and diagnostic performance.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective: This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery. Methods: This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression. Results: Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability. Conclusion Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.