NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective:To evaluate the safety and effectiveness of rubber band-assisted endoscopic submucosal excavation (RB-ESE) for gastric submucosal tumors (SMT).Methods:A retrospective study was conducted on data of gastric SMT patients who underwent ESE in Affiliated Hospital of Yangzhou University from January 2017 to August 2022. A total of 48 patients were selected and divided into two groups: RB-ESE group ( n=20) and the conventional ESE (C-ESE) group ( n=28). The operation time, bleeding rate and perforation rate during operation, the retention rate of the mucosal cap, the number of clips, postoperative complications, and the hospitalization time were analyzed. Additionally, correlations between complications and tumor size/location and between bleeding and perforation were evaluated. Results:No significant difference was found in the general conditions between the two groups ( P>0.05). The operation time of RB-ESE group (14.82±2.31 min) was significantly shorter than that of C-ESE group (23.70±3.67 min) ( t=-9.539, P<0.001). The intraoperative bleeding rates were 20.0% (4/20) and 42.9% (12/28) in the RB-ESE group and C-ESE group respectively ( χ2=2.743, P=0.098), while the intraoperative perforation rates were 25.0% (5/20) and 46.4% (13/28) respectively ( χ2=2.286, P=0.131). Furthermore, the mucosal cap preservation rate was notably higher in the RB-ESE group at 60.0% (12/20) compared with 7.1% (2/28) in the C-ESE group ( χ2=15.777, P<0.001). The number of clips applied to close the wound was 8.05±1.40 and 10.43±1.96 in the RB-ESE group and C-ESE group respectively ( t=4.925, P<0.001). The postoperative hospital stays were 4.35±0.75 days and 5.00±0.86 days respectively in two groups ( t=2.724, P=0.009). No postoperative bleeding or perforation occurred in either group. The results showed that the occurrence of perforation and bleeding were associated with tumor diameter. Patients with tumor size ≥2 cm showed increased proportions of intraoperative bleeding [68.4% (13/19), P<0.001] and perforation [78.9% (15/19), P<0.001]. There was a correlation between intraoperative bleeding and perforation ( P<0.001). Conclusion:RB-ESE proves to be an effective and safe approach for managing gastric SMT, offering advantages such as reduced operation time and hospital stays, improved retention of the mucosal cap post-operation, and less clips use. The results suggest that RB-ESE could be widely adopted for treating SMT.

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 risk factors for lower extremity deep vein thrombosis (DVT) in patients with a spinal cord injury (SCI).Methods:The medical records of 276 hospitalized SCI patients were analyzed retrospectively. They were divided into a DVT group ( n=63) and a no-DVT group ( n=213). Gender, age, blood type, smoking history, surgical history, the time from SCI to admission, cause of SCI, fracture, SCI segments, American Spinal Cord Injury Association grade and complications were compared between the two groups. Binomial logistic regression was used to isolate the risk factors for lower extremity DVT among such patients. Results:Among 84% of the 63 with a lower extremity DVT, it was a calf muscle venous thrombosis. Anemia, hyponatremia and time from SCI to admission (which ranged from 74 to 195 days) were the most serious DVT risk factors.Conclusions:SCI patients are of high risk for DVT, with anemia and hyponatremia being independent risk factors.

Objective:To explore the risk factors for urinary tract infection (UTI) after a spinal cord injury (SCI).Methods:The medical records of 403 SCI patients were analyzed retrospectively. They were divided into UTI group and no-UTI group according to whether they had a UTI at admission. Gender, age, cause of injury, injury level of the spinal cord, voluntary anal contraction, time from injury to admission, American Spinal Injury Association (ASIA) grade, axillary temperature at admission, complications at admission (diabetes, hypertension, fracture of the pelvis, pressure sores or anemia), white blood cell count and urinary bacteria were compared between the two groups. Binary logistic regression was used to highlight the risk factors for a UTI after an SCI.Results:Of the 354 patients included in the final analysis, 62 (17.51%) had a UTI at admission. The regression showed that UTI after an SCI was closely related to an inability to voluntarily contract the anus, anemia, elevated white blood cell count and a high level of bacteria in the urine.Conclusions:Inability to contract the anus, fever, anemia and an elevated white blood cell count are independent indicators of a UTI after an SCI. A temperature ≥37.3°C is a simple indicator of a concentration of bacteria in the urine ≥1266/μL.