1.Bioinformatics Analysis for Structure and Function of Common and Novel Cytochrome P4502C9 Variants
Qiuyue LAN ; Jianping CAI ; Dapeng DAI
Journal of Medical Research 2024;53(10):67-73
Objective Bioinformatics tools were used to conduct a prediction analysis of common CYP2C9 variants(*3)and new variants(*76-*85)in our population,aiming to illustrate the impact of amino acid variants on the multidimensional aspects of CYP2C9 protein structure,properties,and functions.Methods The physicochemical properties,glycosylation and phosphorylation mod-ification,important structural domains,spatial structure and functional changes,and docking mode with the probe drug,tolbutamide,were predicted for each variant by applying various analytical tools.Results Compared with CYP2C9*1,the variants showed different degrees and multiple levels of alterations in amino acid sequence,local structural domains,phosphorylation sites,physicochemical proper-ties,tertiary structure,and docking patterns with substrates.*76 and*84 showed local structure,overall spatial structure,and function disruptions,and they were also correlated with disease outbreaks.*78-*79 and*81-*82 variants showed significant heterogeneity in the predicted results at different levels;*85 had an early termination codon and deletion of most critical structural domains due to a code-shift mutation,and the results suggested that it might affect the protein translation and the assembly of the whole enzyme.The pre-dicted results of the physicochemical properties,local structural domains,and stability of*3 were all non-significantly altered in com-parison with*1;however,docking results showed that*3 protein and tolbutamide were significantly changed in the shape,three-di-mensional size,and contact pattern of the docking pocket.Conclusion This study analyzed the effects of amino acid variants on pheno-types from multiple perspectives and levels,including protein primary,secondary,and tertiary structures,holoenzyme-drug docking,physicochemical properties,and functions,which provides essential references and new interpretative perspectives for future structural elu-cidation,ex vivo and in vivo drug metabolism experiments,and individualized dosing of CYP2C9 variants.
2.Pretheranostic agents with extraordinaryNIRF/photoacoustic imaging performanceand photothermal oncotherapy efficacy.
Liu SHI ; Zhenzhou CHEN ; Jiaxin OU ; En LIANG ; Zhipeng CHEN ; Qiuyue FU ; Lan HUANG ; Kui CHENG
Acta Pharmaceutica Sinica B 2024;14(12):5370-5381
Cervical cancer, the most common gynecological malignancy, significantly and adversely affects women's physical health and well-being. Traditional surgical interventions and chemotherapy, while potentially effective, often entail serious side effects that have led to an urgent need for novel therapeutic methods. Photothermal therapy (PTT) has emerged as a promising approach due to its ability to minimize damage to healthy tissue. Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects. In this study, we developed a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe, S-NBD, which demonstrated robust PTT performance. This innovative probe is capable of activating NIRF/PA signals to enable the detection of biothiols with high emission wavelength (838 nm) and large Stokes shift (178 nm), allowing for in vivo monitoring of cancer cells. Additionally, the probe achieved an outstanding photothermal conversion efficiency of 67.1%. The application of laser irradiation (660 nm, 1.0 W/cm2, 5 min) was able to achieve complete tumor ablation without recurrence. In summary, this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging, incorporating features from PTT for the first time. This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.
3.Application of "disease-characteristics nursing quality improvement" program in the nursing of peritonitis-related peritoneal dialysis
Ying XU ; Qiuyue LIU ; Tianjiao LIU ; Suping LUO ; Yanming DING ; Lan WANG
Chinese Journal of Modern Nursing 2017;23(2):162-166
Objective To reduce the incidence rate of peritonitis by using "disease-characteristics nursing quality improvement" program(DNQIP)of peritonitis-related peritoneal dialysis.Methods A specialized administration group drew up a blueprint of DNQIP on peritonitis-related peritoneal dialysis in 2011. Continuing quality improvement was given to long-term followed-up patients from 2012 to 2015,and the incidence rate of peritonitis was calculated. Harmony degree,initiative,sense of responsibility,communication ability,emotion,team spirit,competence in dealing issues,and work load of specialized nurses before and after the implementation of project were evaluated.Results The incidence rates of peritonitis were 64.38,66.43, 73.13,and 84.97 patient/month in 2012,2013,2014,and 2015. Nurses self-evaluation results showed that the score of competence in dealing issues in 2012 was(3.75±0.50),the score had risen in 2015(4.75±0.50) (P=0.046). The difference in other aspects was not significant(P>0.05).Conclusions DNQIP in peritonitis-related peritoneal dialysis is effective in reducing general incidence rate of peritonitis,and improving the competence of dealing issues for nurses and promoting the regular update of clinical nursing.

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