BACKGROUND: Cluster of differentiation 8 positive (CD8 + ) T cells play a crucial role in the response against tumors, including hepatocellular carcinoma (HCC), where their dysfunction is commonly observed. While the association between elevated peroxisome proliferator-activated receptor alpha (PPARα) expression in HCC cells and exosomes and unfavorable prognosis in HCC patients is well-established, the underlying biological mechanisms by which PPARα induces CD8 + T cell exhaustion mediated by HCC exosomes remain poorly understood. METHODS: Bioinformatics analyses and dual-luciferase reporter assays were used to investigate the regulation of microRNA-27b-3p ( miR-27b-3p ) and thymocyte selection-associated high mobility group box ( Tox ) by Pparα . In vitro and in vivo experiments were conducted to validate the effects of HCC-derived exosomes, miR-27b-3p overexpression, and Pparα on T cell function. Exosome characterization was confirmed using transmission electron microscopy, Western blotting, and particle size analysis. Exosome tracing was performed using small animal in vivo imaging and confocal microscopy. The expression levels of miR-27b-3p , Pparα , and T cell exhaustion-related molecules ( Tox , Havcr2 , and Pdcd1 ) were detected using quantitative reverse transcription polymerase chain reaction analysis, Western blotting analysis, immunofluorescence staining, and flow cytometry analysis. RESULTS: Pparα expression was significantly increased in HCC and negatively correlated with prognosis. It showed a positive correlation with Tox and a negative correlation with miR-27b-3p . The overexpressed Pparα from HCC cells was delivered to CD8 + T cells via exosomes, which absorbed miR-27b-3p both in vitro and in vivo , acting as "miRNA sponges". Further experiments demonstrated that Pparα can inhibit the negative regulation of Tox mediated by miR-27b-3p through binding to its 3'untranslated regions. CONCLUSIONS HCC-derived exosomes deliver Pparα to T cells and promote CD8 + T cell exhaustion and malignant progression of HCC via the miR-27b-3p /TOX regulatory axis. The mechanisms underlying T-cell exhaustion in HCC can be utilized for the advancement of anticancer therapies.
MicroRNAs/metabolism* ; PPAR alpha/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; CD8-Positive T-Lymphocytes/immunology* ; Exosomes/metabolism* ; Animals ; Cell Line, Tumor ; Mice ; High Mobility Group Proteins/genetics* ; Male ; T-Cell Exhaustion

Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
Humans ; Silicosis/genetics* ; Macrophages/cytology* ; Epithelial Cells/pathology* ; GTP-Binding Proteins/physiology* ; Epithelial-Mesenchymal Transition ; Disease Progression ; Cell Line ; Male

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE To investigate the current status of self-medication behaviors and the demand preferences for pharmaceutical services among residents in Xining， providing a basis for developing pharmaceutical service intervention strategies tailored to regional characteristics. METHODS A self-designed questionnaire， developed based on literature review and revised after expert panel discussion and a pre-survey， was used to conduct anonymous surveys among residents purchasing medicines at 12 retail pharmacies in Xining area from April 2023 to April 2024. Descriptive analysis， Chi-square test， and Spearman correlation analysis were employed to analyze the characteristics and influencing factors of residents’ self-medication behaviors， and pharmaceutical service needs. RESULTS A total of 859 valid questionnaires were collected， with 605 respondents （70.43%） reporting self-medication behaviors. The primary reason for self-medication was mild symptoms （46.94%）. The main conditions treated were gastrointestinal discomfort （38.51%） and cold， fever， headache （35.37%）. Chinese patent medicines were the most commonly used （58.68%）. Drug selection relied mainly on recommendations by pharmacy staff （52.07%）， and retail pharmacies were the primary source of medicines （65.95%）. Dosage and administration were determined primarily by referring to the drug package insert （67.27%）， while a minority relied on personal experience （9.92%）. Notably， 20.33% of respondents never read the package insert before medication， with a higher tendency observed among ethnic minorities， farmers， and individuals with chronic diseases （P＜0.05）. While 65.29% of respondents reported partially understanding the insert content， those aged ≥60 years， ethnic minorities， and individuals with chronic diseases qhsrmyy-28） were more likely to report being completely unable to understand it （P＜0.05）. Self-medication was “often effective” for 52.73% of respondents， whereas 7.77%“ often experienced adverse drug reactions”； farmers were more prone to poor efficacy or adverse reactions （P＜0.05）. A majority （72.89%） of respondents residents believed it necessary to learn about self- medication knowledge， and 47.11% preferred to obtain pharmaceutical services through WeChat public accounts or mobile applications （APP）. CONCLUSIONS Self-medication is common among residents in Xining area. Issues such as neglecting to read package inserts and relying on personal experience are evident. It is essential to develop science popularization programs suitable for the characteristics of the local population and utilize digital platforms like WeChat public accounts and APP to disseminate self- medication knowledge， thereby enhancing residents’ awareness and capacity for rational medication use.

Objective To investigate the safety and feasibility of peripheral vascular intervention via the ipsilateral transulnar access(TUA)due to failure of transradial access(TRA)puncture.Methods The clinical data of 2546 peripheral vascular interventions via TRA,which were performed at authors'hospital between January 2019 and December 2021,were retrospectively analyzed.Among the 2546 interventions,TRA puncture failed in 37 procedures,and in 27 of these patients the ipsilateral TUA puncture had to be adopted.The puncture success rate,surgical success rate and puncture approach-related complications of TUA of the 27 patients receiving ipsilateral TUA puncture were analyzed.Results The success rate of ipsilateral TUA puncture after TRA puncture failed was 96.3％(26/27),and in one patient transfemoral access(TFA)puncture had to be substituted because of the ulnar artery spasm.The total success rate of interventional procedures was 96.3％(26/27).No serious complications occurred,and the incidence of minor complications was 19.2％(5/26).Conclusion Preliminary results indicate that for the experienced TRA operators,using ipsilateral TUA puncture due to failure of TRA puncture is a safe and feasible strategy choice.

【Objective】 To investigate the recurrence of patients with renal cell carcinoma (RCC) after robot-assisted partial nephrectomy (RAPN), and to explore the related factors of recurrence. 【Methods】 Clinical data of 367 RCC patients who underwent RAPN during 2015 and 2020 in our hospital were retrospectively collected. Patients were divided into recurrence group and non-recurrence group. The related factors of recurrence and 5-year cumulative recurrence rate of RCC and clear cell renal cell carcinoma (ccRCC) in the recurrence group were analyzed. 【Results】 The median follow-up was 48 (IQR:38-60) months. Recurrence occurred in 9 patients, with a 5-year cumulative recurrence rate of 97.5%. For RCC patients, univariate analysis showed that tumor size, T-stage, R. E. N. A. L. score, R value, N value, and operation time were significantly associated with postoperative recurrence (P<0.05), while multivariate analysis showed that N value (HR=15.75, 95%CI:2.00-124.17, P=0.009) was an independent related factor. For ccRCC patients, univariate analysis showed that hypertension, tumor size, T-stage, R. E. N. A. L. score, N value, operation time and WHO/ISUP grade were significantly associated with postoperative recurrence (P<0.05), while multivariate analysis showed that WHO/ISUP grade (HR=4.99, 95%CI:1.04-24.01, P=0.045) was an independent related factor. 【Conclusion】 The 5-year cumulative recurrence rate of RCC patients after RAPN is 2.5%. N value and WHO/ISUP grade are the independent related factor of recurrence of RCC and ccRCC, respectively.

【Objective】 To explore the influencing factors of planned robot-assisted partial nephrectomy (RAPN) converted to radical nephrectomy (RN). 【Methods】 Clinical data and operation records of 488 patients planned for RAPN in our hospital during 2015 and 2020 were retrospectively collected. The patients were divided into converted and unconverted groups, and relevant clinical data of the two groups were compared. The causes and influencing factors for conversion were analyzed. 【Results】 Among the 488 patients, 14 (2.9%) converted to RN. The causes included: ①complicated tumor anatomy and surgical difficulties; ②local advanced renal tumor suspected during operation; ③severe intraoperative hemorrhage. Univariate analysis showed that R. E. N. A. L score (P<0.001), E value (P<0.001), N value (P<0.001), L value (P<0.001), renal hilum position (P<0.001) and T stage (P=0.002) were influencing factors of conversion. 【Conclusion】 Causes for the conversion of RAPN to RN include complicated tumor anatomy, suspected local advanced renal tumor and severe intraoperative hemorrhage. The R. E. N. A. L score, E value, N value, L value, renal hilum position and T stage are influencing factors.

【Objective】 To compare the clinical efficacy of robot-assisted and open surgery in the treatment of renal carcinoma with inferior vena cava cancer thrombus, and to analyze the safety and feasibility of robot-assisted radical nephrectomy. 【Methods】 Clinical data of 55 patients surgically treated for renal carcinoma with Mayo Ⅰ-Ⅲ inferior vena cava tumor thrombus during Dec.2015 and Dec.2021 were retrospectively analyzed. Based on the operation methods, the patients were divided into the robotic surgery group (n=36) and open surgery group (n=19). The perioperative data, oncological results and survival of the two groups were compared. 【Results】 All operations were successful. The median operation time was 176 (IQR:137-234) min, and grade Ⅲ and above complications occurred in 9(16.4%) cases. The robotic surgery group had lower intraoperative blood loss [300 (IQR:200-625) mL vs.1 000 (IQR:600-1 184) mL] and blood transfusion ratio [(20/36) vs. (18/19)] than the open surgery group, but higher postoperative hemoglobin level[109(98-120) g/L vs. 90(84-100) g/L]. During a median follow-up of 26 (IQR:19-39) months, 19(34.5%) patients developed new metastases and 12(21.8%) patients died. The postoperative tumor-specific survival (HR=0.39, 95%CI:0.13-1.16, P=0.090) and overall survival (HR=0.71, 95%CI:0.22-2.23,P=0.554) were not significantly different between the two groups. 【Conclusion】 There are no significant differences in the incidence of postoperative complications, tumor-specific survival and overall survival between robot-assisted and open surgery for Mayo Ⅰ-Ⅲ inferior vena cava tumor thrombus, but the intraoperative blood loss in robotic group is lower than that in the open surgery group.

【Objective】 To compare the feasibility, safety, and efficacy of robot-assisted and open radical nephrectomy for complex kidney neoplasm >8 cm in diameter. 【Methods】 Clinical data of 24 patients with large kidney neoplasm undergoing robot-assisted radical nephrectomy (9 cases, 37.5%) and open radical nephrectomy (15 cases, 62.5%) during Nov.2015 and Aug.2019 were retrospectively analyzed. The surgical parameters, perioperative complications and follow-up outcomes were compared between the two groups. 【Results】 All operations were successful. Compared with the robot group, the open group had a higher incidence of clinical symptoms (93.3% vs.44.4%, P=0.015) and larger maximum tumor diameter (124 mm vs.95 mm, P=0.021). There were no significant differences in other preoperative characteristics between the two groups. The robot group had less intraoperative blood loss (100 mL vs.800 mL, P=0.006) and lower blood transfusion rate (0% vs. 60.0%, P=0.007) than the open group. During the median follow-up of 50 (range: 25-67) months, 4 patients in the open group and 1 in the robot group developed new metastases, and 4 patients in the open group died due to advanced tumor stage. 【Conclusion】 Robot-assisted radical nephrectomy is safe in the treatment of complex and large renal tumors, and causes less intraoperative blood loss than open surgery.

Objective: A prognostic risk model for lung adenocarcinoma patients was established based on the cancer genome atlas(TCGA) database to explore the prognostic performance of autophagy related gene risk model for lung adenocarcinoma patients and its correlation with immune microenvironment． Methods: Clinical information and transcriptome data of lung adenocarcinoma patients were downloaded and extracted from TCGA database，and 232 autophagy-related genes were screened from the human autophagy database．cox regression analysis was used to screen out four autophagy genes independently associated with prognosis．The prognostic prediction model of lung adenocarcinoma was constructed by risk score ，and the performance of prediction model was evaluated by ROC curve．The relationship between risk scores and tumor immune microenvironment was explored using ESTIMATE ( estimation of stromal and immune cells in malignant tumour tissues using expression data) and CIBERSORT algo- rithms. Results: Thirty differentially expressed autophagy-related genes were identified in lung adenocarcinoma， of which four autophagy genes (BIRC5，ERO1A，ITGB4，NLRC4 ) could predict the prognosis of the patients. Grouped by risk score，the Kaplan-Meier analysis demonstrated that the survival rate of high-risk group was signifi- cantly lower than that of low-risk group(P＜0. 000 1) ．The ROC curve proved the accuracy of the model in predic- ting the prognosis of lung adenocarcinoma ( AUC = 0. 757 ) ．The ESTIMATE and CIBERSORT analyses revealed that the risk scoring model was associated with multiple immune cells and immune infiltrates in the tumor microenvi- ronment． Conclusion Compared with clinical data，the autophagy gene prognostic risk model can better predict the prognosis of patients with lung adenocarcinoma．In the high-risk group，CD4 + memory quiescent cells can im- prove prognosis in lung adenocarcinoma patients.