Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective To observe the value of apparent diffusion coefficient(ADC)for quantitatively evaluating progressive muscle injury of rabbit limbs in early stage of high-voltage electrical burn.Methods Twenty healthy adult rabbits were selected to establish limb high-voltage electrical burn models,which were randomly divided into 0.5,24,48 and 72 h groups(each n=5).MR diffusion weighted imaging(DWI)was collected for each group at 0.5,24,48 and 72 h after modeling,and the injured core muscles of the right hind limb and the normal muscles of the contralateral limb were taken for HE staining.The muscle's ADC,muscle fiber density(MFD)and muscle fiber diameter(D)values at the injured core of current entry and exit were compared,and those of normal muscle were also analyzed.The correlations of ADC values in injured core muscle and MFD or D values were investigated.Results There were significant differences of ADC values of injured core muscle at both the entry and exit and normal muscle,also of ADC values of injured core muscle at the entry and exit within each group(all P＜0.05).ADC values of injured core muscle at the entry and exit decreased with time going(all P＜0.05),but ADC values of normal muscle were not significantly different among different time points(P＞0.05).MFD values of injured core muscle at the entry and exit decreased with time going(all P＜0.05),while MFD values of the normal muscle,D values of the injured core muscle at the entry and exit and normal muscle were not significantly different among time points(all P＞0.05).ADC value of the injured core muscle was positively correlated with MFD value and negatively correlated with D value(rs=0.846,r=-0.507,both P＜0.05).Conclusion ADC could quantitatively evaluate the progressive muscle injury of rabbit limbs in early stage of high-voltage electrical burn.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Objective:To explore the value of matrix metalloproteinase (MMP) in differential diagnosis of brucellosis spondylitis (BS) and tuberculous spondylitis (TS).Methods:Retrospective analysis was used to collect the data of patients with BS and TS diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to December 2018. Magnetic resonance imaging (MRI), laboratory data, and the expression levels of MMP-2 and MMP-9 were analyzed.Results:There existed significant differences in imaging findings like the infection levels, the number of infected vertebrae and the paravertebral soft tissue lesions between BS and TS patients ( n=26, 27, P < 0.05). Basophils in BS patients were significantly higher than those in TS patients [(0.022±0.019) × 10 9 number/L vs (0.017±0.007) × 10 9 number/L, t=2.19, P < 0.05]; but the C-reactive protein of BS patients was significantly lower than that of TS patients [(16.12±14.16) mg/L vs (33.78±24.05) mg/L, t=2.45, P < 0.05]. The expression of MMP-9 in BS patients was significantly lower than that in TS patients [76.92% (20/26) vs 96.30% (26/27), χ 2=4.34, P < 0.05], but there was no significant difference in the expression of MMP-2 ( P > 0.05). Conclusion:MMP-9 may be a new biomarker in differential diagnosis of BS and TS, which can be helpful for the differential diagnosis of BS and TS by combining MRI findings with laboratory findings.

Objective To construct and implement theSTARnurse training model, and discuss its application effect and the problems that should be paid attention to, and to provide operational cases and practical basis for nursing clinical education. Methods Through literature review and expert consultation, the framework and content of STAR nurse training model were set up and implemented. The questionnaire survey and semi structured in-depth interviews were conducted among the nurses in the hospital to evaluate the effect of improving the nurses′self-directed learning ability. Results After the implementation of the project, the scores of the three dimensions of self-management, desire for study and self-control were (3.67±0.57), (4.05±0.54), (3.99±0.50) points, which were higher than (3.55±0.49), (3.71± 0.52), (3.53±0.42) points before implementation. The difference was statistically significant (P<0.05 or 0.01). The semi structured in-depth interviews showed that all the nurses believed that STAR nurse training model could promote independent learning and stimulate interest in learning. 14 nurses thought it was beneficial for the nurses to find the problems. Conclusions STAR nurse training model can create a favorable learning environment for nurses, and stimulate the learning motivation. It plays a positive role in improving nurses′ability of self-directed learning.

Objective To observe the effects of atorvastatin on the microglia activation after traumatic brain injury (TBI). Methods Sixty adult male C57/BL6 mice were randomly divided into sham group, atorvastatin group and saline group, 20 mice for each group. The atorvastatin group and saline group were given hydraulic combat to establish TBI mouse model. The shame group underwent the same surgical procedure without being exposed to percussion injury. The atorvastatin group was treated with atorvastatin (orally, 1 mg/kg)1 h after TBI and for 7 consecutive days. The saline group was given sa?line orally. The expression of microglia (Iba-1+) at the 1st, 3rd, and 7th day after TBI and matrix metalloproteinase-9 (MMP-9) around the lesion at the 3rd day after TBI were detected by immunohistochemical staining. Tumor necrosis factor (TNF)-αwas detected by Western blot assay at the 3rd day after TBI. Results The positive expression of Iba-1+microglia was signifi?cantly decreased in atorvastatin group than that of saline group at the 1st, 3rd, and 7th day after TBI (80.00±7.44 vs. 118.40± 6.65,85.60±10.87 vs. 189.00±7.51,69.40±5.54 vs. 102.40±10.89, P<0.05). The positive expression of MMP-9 was signifi?cantly decreased in atorvastatin group compared with that of saline group at the 3rd day after TBI (86.80 ± 8.40 vs. 133.80 ± 8.46, P<0.05). Results of Western blot assay showed that the positive expression of TNF-αwas significantly decreased in astorvastatin group than that of saline group at the 3rd day after TBI (0.64±0.01 vs. 0.97±0.02,P<0.05). Conclusion Ator?vastatin can reduce inflammation factor by influencing the microglia activation after TBI in mice.

OBJECTIVETo explore the preoperative diagnostic value of ¹⁸F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (¹⁸F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis.

METHODSClinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent ¹⁸F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and ¹⁸F-FDG PET-ceCT were calculated.

RESULTSA total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign, of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT, ceCT and ¹⁸F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%, 100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Kappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Kappa value -0.005, 0.305, 0.848). The area under curve(AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651(95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for ¹⁸F-FDG PET-ceCT respectively. The AUC of ¹⁸F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05).

CONCLUSION(18)F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.

Objective To explore the preoperative diagnostic value of 18F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (18F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis. Methods Clinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent 18F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and 18F-FDG PET-ceCT were calculated. Results A total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign , of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT , ceCT and 18F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%,100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Κappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Κappa value -0.005, 0.305, 0.848). The area under curve (AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651 (95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for 18F-FDG PET-ceCT respectively. The AUC of 18F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05). Conclusion 18F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.

Objective To explore the preoperative diagnostic value of 18F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (18F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis. Methods Clinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent 18F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and 18F-FDG PET-ceCT were calculated. Results A total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign , of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT , ceCT and 18F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%,100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Κappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Κappa value -0.005, 0.305, 0.848). The area under curve (AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651 (95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for 18F-FDG PET-ceCT respectively. The AUC of 18F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05). Conclusion 18F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.