Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To observe the efficacy and safety of different doses of remifentanil combined with sevoflurane in patients undergoing spinal surgery.Methods Patients undergoing spinal surgery were divided into low dose group,medium dose group and high dose group.Low dose group,medium dose group and high dose group were given 0.2,0.4 and 0.6 μg·kg-1·min-1 remifentanil by intravenous pump,respectively.Pain status[visual analogue score(VAS)],analgesic drug use,quality of recovery,hemodynamic indexes at different times[before surgery(T0),immediately after intubation(T1),intravenous pump injection of remifentanil 5 min(T2),10 min(T3),15 min(T4)]of the 3 groups were compared;and safety was evaluated.Results The low,medium and high dose groups were enrolled in 49,56 and 51 patients,respectively;the VAS scores at 6,12 and 24 h after operation in the low dose group were(2.48±0.51),(2.73±0.63)and(2.61±0.54)points,respectively;the VAS scores in the medium dose group were(2.36±0.54),(2.65±0.59)and(2.51±0.50)points,respectively;the VAS scores in the high dose group were(2.29±0.53),(2.53±0.57)and(2.44±0.52)points,respectively.There was no statistically significant difference between the groups(all P＞0.05).The number of patient-controlled analgesia pump compressions in the low,medium and high dose groups were(3.27±0.96),(3.02±0.90)and(2.89±0.71)times,respectively;the number of remedial analgesia cases was 2 cases(4.08％),2 cases(3.57％)and 0 cases(0.00％),respectively.There was no statistically significant difference(all P＞0.05).The recovery time of low,medium and high dose groups were(7.05±1.65),(8.24±2.17)and(9.03±2.48)min,respectively;the recovery time of consciousness were(11.26±2.73),(13.85±2.94)and(15.57±3.17)min,respectively;the extubation time were(16.34±3.05),(18.72±3.29)and(20.34±3.58)min,respectively.The differences were statistically significant(all P＜0.05).There was no significant difference in blood oxygen saturation(SpO2),mean arterial pressure and heart rate at time points of T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Adverse drug reactions in the 3 groups were mainly hypotension,nausea and vomiting,bradycardia,etc.The total incidence of adverse drug reactions in the high,medium and low dose groups was 11.76％(6 cases/51 cases),7.14％(4 cases/56 cases)and 8.16％(4 cases/49 cases),respectively.There were no statistically significant differences(P＞0.05).Conclusion 0.2 μg·kg-1·min-1 remifentanil combined sevoflurane has better recovery quality and high safety in spinal surgery patients.

The processing of traditional Chinese medicine(TCM) is a core theory within TCM, embodying deep philosophical, cultural, and natural scientific wisdom. Among the various techniques, the "synergistic processing of medicinal materials and excipients" has garnered significant attention due to its uniqueness. This study explored the impact of the adjuvant Glycyrrhizae Radix et Rhizoma on the dynamic process of component transformation during the processing of Aconiti Lateralis Radix Praeparata using techniques such as acidic dye colorimetry, UPLC-Q-TOF-MS/MS, density functional theory(DFT), and molecular dynamics simulations(MDS). The research revealed that during processing, various alkaloid components in Aconiti Lateralis Radix Praeparata exhibited different weak interactions with glycyrrhizic acid in Glycyrrhizae Radix et Rhizoma, affecting the transformation and content changes of alkaloid components such as aconitine, hypaconitine, and other diester-type alkaloids. This study, based on the dynamic process of "interactions between excipients and herbal medicine and component transformation", elucidated the intrinsic mechanism of processing of Aconiti Lateralis Radix Praeparata with Glycyrrhizae Radix et Rhizoma and provided a reference for understanding the scientific principles underlying the excipient processing of TCM.
Drugs, Chinese Herbal/chemistry* ; Aconitum/chemistry* ; Excipients/chemistry* ; Glycyrrhiza/chemistry* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Molecular Dynamics Simulation ; Alkaloids/chemistry* ; Glycyrrhizic Acid/chemistry*

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.

Animals ; Genomics ; Humans ; Serogroup ; Streptococcal Infections ; Streptococcus suis/isolation & purification* ; Swine ; Swine Diseases

Objective:This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) .Methods:The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information.Results:Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations ( HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations ( HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations ( HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis ( P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS ( P<0.001) and OS ( P=0.006) . Conclusion:Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.