1.Association between sleep characteristics, physical activity patterns with depressive and anxiety symptoms in college students
Chinese Journal of School Health 2025;46(4):552-557
Objective:
To explore the relationship between sleep characteristics, physical activity patterns, with depressive and anxiety symptoms in college students, so as to provide reference for student mental health promotion.
Methods:
From September to November 2023, a convenience sampling method was used to select 7 954 college students aged 18-22 years from 9 universities in Shanghai, Hubei, and Jiangxi. Assessments were conducted using the International Physical Activity Questionnaire Short-Form (IPAQ-SF), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI) to evaluate physical activity, depressive and anxiety symptoms, and sleep quality, respectively. Logistic regression analysis was employed to explore the impact of sleep characteristics and physical activity patterns on depressive and anxiety symptoms and their comorbidity among college students.
Results:
The detection rates for depressive symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms were 25.67%, 35.39%, and 23.15%, respectively. Factors such as gender, grade, household registration, parental education level, annual family income, family structure, and dietary habits were all associated with the detection rates of depressive and anxiety symptoms and their comorbidity (χ2=4.41-118.39, P<0.05). Physical activity patterns, sleep duration, sleep quality, and sleepwake characteristics were also associated with the occurrence of depressive and anxiety symptoms and their comorbidity (χ2=9.66-627.70, P<0.05). Logistic regression analysis showed that college students who stayed up late and slept less than 7 had the highest risk of depressive and anxiety symptoms and their comorbidity (OR=1.93, 1.85, 1.88, P<0.05). Compared to regular physical activity patterns, insufficient physical activity patterns were associated with an increased risk of depressive and anxiety symptoms (all OR=1.18, P<0.05). Further stratified analysis results showed that the risk of depression, anxiety and their comorbidity increased in college students who stayed up late and slept less than 7 h, went to bed before midnight and slept less than 7 h, or went to bed before midnight and slept more than 7 h but did not have sufficient physical activity (P<0.05).
Conclusions
Sleep characteristics and physical activity patterns significantly affect depressive and anxiety symptoms in college students. Universities should strengthen sleep management and implement flexible physical activity interventions to help students establish healthy lifestyles.
2.Mechanism of Qizhu Kang'ai Prescription for Inhibiting Proliferation of Hepatocellular Carcinoma by Regulating Tumor Metabolic Reprogramming via PCK1/Akt/p21 Signal Axis
Xin ZHONG ; Rui HU ; Jing LI ; Lanfen PENG ; Xingning LIU ; Qi HUANG ; Jialing SUN ; Xinfeng SUN ; Jianping CHEN ; Benqiang CAI ; Xiaozhou ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):26-36
ObjectiveTo study the effect of Qizhu Kang'ai prescription (QZAP) on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver of mouse model of liver cancer induced by diethylnitrosamine (DEN) combined with carbon tetrachloride (CCl4) and Huh7 cells of human liver cancer, so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group, a model group, and a QZAP group were set up, in which QZAP (3.51 g·kg-1) or an equal volume of normal saline was administered daily by gavage, respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and alpha-fetoprotein (AFP) in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin (HE) staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment, Huh7 cells were divided into blank group, QZAP low, medium, and high dose groups and/or PCK1 inhibitor (SKF-34288 hydrochloride) group, and Sorafenib group. The corresponding drug-containing serum and drug treatment were given, respectively. Cell counting kit-8 (CCK-8) method, colony formation experiment, Edu fluorescent labeling detection, intracellular adenosine triphosphate (ATP) content detection, and cell cycle flow cytometry detection were used to evaluate the proliferation ability, energy metabolism changes, and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1, serine/threonine kinase (Akt), phosphorylated Akt (p-Akt), and cell cycle-dependent protein kinase inhibitor 1A (p21). ResultCompared with the model group, the pathological changes such as cell atypia, necrosis, and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated, and the number of liver tumors was reduced (P<0.01). The serum ALT, AST, γ-GT, and AFP levels were reduced (P<0.01). At the cell level, compared with the blank group, low, medium, and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells (P<0.01) and the number of positive cells with Edu labeling (P<0.01) and inhibit clonal proliferation ability (P<0.01). The QZAP groups could also reduce the intracellular ATP content (P<0.05) and increase the distribution ratio of the G0/G1 phase of the cell cycle (P<0.05) in a dose-dependent manner. Compared with the model group and blank group, PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced (P<0.05,P<0.01), and the p-Akt protein level was significantly increased (P<0.01). Compared with the blank group, the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased (P<0.05), but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group, the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content, cell survival rate, and Edu-positive cell ratio of Huh7 cells (P<0.05) and significantly increased the G0/G1 phase distribution proportion (P<0.05). ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression, thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.
3.Construction of a BAC Vector and Its Application for Haplotype Analysis of CYP2A6
Fangling ZHAO ; Yuying QI ; Jianping CAI
Journal of Medical Research 2024;53(2):24-28,111
Objective To construct one high-copy BAC vector with cloning capacity for large DNA fragment insertion and use it for the haplotype analysis of CYP2A6 gene.Methods Oligos including multiple cloning sites were annealed and ligated into the Hind Ⅲ/BamH Ⅰ site of pGEM-3Z and pBeloBACll,separately.Then,the intermediate vectors were digested by Hind Ⅲ and ligated together,so as to get the head-to-tail oriented high-copy BAC vector pBAC-BJH after the blue-white spotting test.STI PCR method was used for the amplification of whole CYP2A6 gene,and purified amplicon was double digested by BstB Ⅰ/Mlu Ⅰ and ligated into the same site of newly constructed vector pBAC-BJH.Several clones were then picked up and sequenced for the haplotype analysis of carriers with newly discovered CYP2A6 variant 355A>T.Results One high-copy BAC vector pBAC-BJH with 7 newly added multiple cloning sites was successfully constructed.High copy number and multiple cloning sites were the advantages of this plasmid.With this vector,haplotype analysis result for 22C>T,51A>G,355A>T in carrier with newly detected CYP2A6mutation was CGT.Conclusion One vector pBAC-BJH convenient for cloning large DNA fragment was successfully developed,and it can be used for the haplotype analysis of cytochrome p450 gene and cloning or sequencing of other genes with large genomic DNA inserts.
4.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
5.Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy
Bolun ZHANG ; Xinyu BI ; Hong ZHAO ; Jianping CHANG ; Xiaoshi ZHANG ; Bowen XU ; Jianjun ZHAO ; Jianguo ZHOU ; Jianqiang CAI
Chinese Journal of Surgery 2024;62(1):49-56
Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.
6.Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy
Bolun ZHANG ; Xinyu BI ; Hong ZHAO ; Jianping CHANG ; Xiaoshi ZHANG ; Bowen XU ; Jianjun ZHAO ; Jianguo ZHOU ; Jianqiang CAI
Chinese Journal of Surgery 2024;62(1):49-56
Objectives:To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model.Methods:This is a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method, patients were randomly divided into a model group( n=166) and a validation group( n=41) according to an 4∶1 ratio. There were 118 males and 48 females in the modeling group,with an age ( M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (range: 25.0 to 81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the related factors of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,validated by internal and external validation of the model. Results:Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT, D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set, and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model( P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806, suggesting that the model had a good generalization prediction ability. Conclusions:The levels of ALT, D-dimer, and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.
7.Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City
Yan HE ; Fangfang XU ; Haijun ZUO ; Wei CHEN ; Zhibin LIU ; Zebang LIU ; Xuezhen CHEN ; Qingshen HUI ; Gengwen ZOU ; Zhenbin CAI ; Yang LIU ; Haoshun TAN ; Hongfeng ZHOU ; Jianping WANG
Chinese Journal of Preventive Medicine 2024;58(7):1020-1028
Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.
8.Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study
Yanchun LUO ; Manlin LANG ; Wenjia CAI ; Zhiyu HAN ; Fangyi LIU ; Zhigang CHENG ; Xiaoling YU ; Jianping DOU ; Xin LI ; Shuilian TAN ; Xuejuan DONG ; Ping LIANG ; Jie YU
Chinese Journal of Hepatology 2024;32(4):332-339
Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?0.001, especially for liver cancer 3.1~5.0 cm ( P ?0.001). Conclusion:Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.
9.Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia
Xiaolin YUAN ; Yibo WU ; Xiaolu SONG ; Yi CHEN ; Ying LU ; Xiaoyu LAI ; Jimin SHI ; Lizhen LIU ; Yanmin ZHAO ; Jian YU ; Luxin YANG ; Jianping LAN ; Zhen CAI ; He HUANG ; Yi LUO
Chinese Journal of Hematology 2024;45(1):41-47
Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.
10.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.


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