Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events.Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population.Clinical data,adverse reactions,and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication.Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions.Furthermore,a prediction model for such adverse reactions was developed,and its predictive efficacy and calibration ability were evaluated using ROC analysis.Results Re-treatment(OR=2.540,P=0.028),coexistence of cavities(OR=4.092,P=0.021),anemia(OR=10.921,P=0.005),and Cmin≥0.7665 mg/L(OR=6.813,P<0.001)are independent risk factors for the occurrence of linezolid-related neurological adverse reactions.The prediction model,based on these four factors,exhibits an AUC of 0.851(95%CI:0.774～0.929),accompanied by a Youden index of 0.590,a sensi-tivity of 66.7%,and a specificity of 92.3%.Moreover,the prediction model demonstrates excellent calibration ability.(Hosmer-lemeshow χ2=8.719,P=0.273).Conclusion In MDR/RR-TB patients,the presence of cavita-tion,retreatment,and anemia may confer a heightened risk of linezolid-related neurological adverse reactions.A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events.

BACKGROUND:Closed reduction and internal fixation are mostly used to treat fracture dislocation of tarsometatarsal joint, but cannot obtain satisfactory repair effect. Redisplacement easily appeared after local sweling subsidence. Therefore, open reduction and internal fixation are actively used in the clinic to treat fracture dislocation of tarsometatarsal joint so as to restore foot function and to elevate quality of life. OBJECTIVE:To explore the clinical effect of open reduction and cannulated screw and Kirschner wire fixation for fracture dislocation of tarsometatarsal joint. METHODS:A total of 42 patients with fracture dislocation of tarsometatarsal joint in the 88 Hospital of Chinese PLA from September 2012 to September 2013 were selected and were given open reduction and cannulated screw and Kirschner wire fixation. After treatment, the recovery of patients was observed, and ankle hindfoot function was assessed with American Orthopaedic Foot and Ankle Society ankle hindfoot score. RESULTS AND CONCLUSION:A total of 42 patients were folowed up for 1-12 months. American Orthopaedic Foot and Ankle Society ankle hindfoot score results showed that there were excelent in 30 cases, good in 10 cases, and poor in 2 cases, and the 2 patients were subjected to high energy soft tissue injury. 37 patients in 4-6 months after operation started weight-bearing walking. Three patients had mild pain, a certain functional limitation, but could maintain normal walking gait. The remaining two patients complicated with traumatic arthritis, and were unable to do normal weight-bearing walking. These results show that open reduction and cannulated screw and Kirschner wire fixation can achieve good effect of anatomical reduction of fracture dislocation of tarsometatarsal joint, and improve patient’s ankle function.