1.Analysis of differential metabolites in different parts of Angelica dahurica( Fisch.ex Hoffm.) Benth. et Hook. f. ex Franch. et Savat. based on untargeted metabolomics
Xing WANG ; Zishan ZHOU ; Enwei TIAN
China Pharmacy 2026;37(9):1161-1166
OBJECTIVE To investigate the metabolic differences in roots, stems and leaves of Angelica dahurica (Fisch.ex Hoffm.) Benth. et Hook. f. ex Franch. et Savat. (shortened for A. dahurica ), and to provide a basis for the development and utilization of its medicinal resources. METHODS UPLC-MS/MS untargeted metabolomics technology was employed to detect metabolites in roots, stems and leaves of A. dahurica . Multivariate statistical analysis was used to screen differential metabolites and perform cluster analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted on these differential metabolites. RESULTS A total of 769 metabolites were identified in roots, stems and leaves of A. dahurica . Among t hem, lipids, alkaloids, amino acids and their derivatives accounted for the highest proportion, which accounted for 14.31%, 13.91% and 13.65%, respectively, and the coumarin compounds accounted for 3.25%. Results of principal component analysis, orthogonal partial least squares-discriminant analysis and cluster analysis indicated that there were certain differences in metabolites among the three tissues. A total of 205 differential metabolites were identified between stems and roots (82 up-regulated and 123 down-regulated), 326 differential metabolites between leaves and roots (247 up-regulated and 79 down-regulated), and 293 differential metabolites between the leaves and stems (263 up-regulated and 30 down-regulated). Further analysis of the differential coumarin metabolites in different plant parts revealed that several compounds, including ( R )-oxypeucedanin, 4-hydroxycoumarin, 4-methylumbelliferyl acetate, exhibited relatively high contents in the leaves. KEGG pathway enrichment analysis indicated that differential metabolites predominantly accumulated in the phenylpropanoid biosynthesis and ABC transporter pathways. CONCLUSIONS There are significant differences in metabolites among roots, stems and leaves of A. dahurica . Coumarin compounds are highly enriched in the leaves, and their synthesis and transport may be related to the synergistic effect of the phenylpropanoid biosynthesis pathway and the ABC transporter pathway.
2.Clinical value of 18F-PSMA-1007 PET/CT combined with serum total prostate specific antigen in predicting International Society of Urological Pathology pathological grading of prostate cancer
Yunfeng BO ; Rongrong TIAN ; Lanlan BAO ; Ming ZHAO ; Jie ZHOU ; He LI ; Hailong HAO ; Enwei XU
Chinese Journal of Oncology 2025;47(2):175-182
Objective:To discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P<0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P<0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P<0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P<0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P<0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P<0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.
3.Correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer
Yunfen BO ; Rongrong TIAN ; Ming ZHAO ; Enwei XU ; Yanfeng XI ; Jie ZHOU ; He LI ; Hailong HAO
Cancer Research and Clinic 2025;37(4):255-261
Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.
4.Correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer
Yunfen BO ; Rongrong TIAN ; Ming ZHAO ; Enwei XU ; Yanfeng XI ; Jie ZHOU ; He LI ; Hailong HAO
Cancer Research and Clinic 2025;37(4):255-261
Objective:To discuss the correlation of pathologic findings after radical prostatectomy and preoperative 18F-PSMA-1007 PET/CT parameters with the prognosis of patients with prostate cancer. Methods:A retrospective case series study was conducted. The clinicopathological data of 48 patients with prostate cancer who underwent radical prostatectomy in Shanxi Province Cancer Hospital between January 2019 and August 2023 were retrospectively analyzed. All patients underwent 18F-PSMA-1007 PET/CT imaging before surgery. The age, the preoperative serum total prostate-specific antigen (tPSA), prostate-specific antigen density (PSAD), prostate volume, tumor diameter, TNM staging, the pathologic data after radical prostatectomy [International Society of Urological Pathology (ISUP) grade, resection margin status, nerve invasion], and preoperative maximum standard uptake value (SUV max) were collected. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of PET/CT parameter SUV max in predicting tumor recurrence after prostate cancer surgery. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier method and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing RFS after radical prostatectomy. Results:All 48 patients were acinar adenocarcinoma. The median level of the patients' serum tPSA was 19.16 (10.50, 30.99) ng/ml; the median prostate volume was 36.20 (31.83, 45.48) ml; the median tumor diameter was 2.80 (1.60, 4.00) cm; the median PSAD was 0.48 (0.31,1.02) ng·ml -1·cm -3. The primary SUV max of prostate cancer was 13.61 (8.10, 20.20) . Of the 48 patients, 1 case died of heart disease and 1 case died of COVID-19 within 3 to 6 months after surgery, and the rest 46 patients were analyzed for prognosis. Among 46 cases, 26 were in the ISUP low-grade group and 20 were in the high-grade group; 17 were positive and 29 were negative for nerve invasion; 7 were positive and 39 were negative for margin status. The median follow-up time was 18.5 (8-64) months. There were 30 recurrence-free patients and 16 recurrent patients by the follow-up in April 2024. The median RFS time was 15 months; and there were statistically significant differences in RSF among the ISUP high-grade and low-grade groups, preoperative SUV max ≥ 16.77 and < 16.77 groups, positive and negative resection margin groups (all P < 0.01). SUV max was positively correlated with ISUP pathological grade and tPSA level ( r value was 0.634, 0.584, respectively; both P < 0.01). The differences in preoperative serum tPSA level, PSAD, tumor diameter, and SUV max were statistically significant between the ISUP low-grade group and the high-grade group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, and tumor diameter were statistically significant between the nerve invasion positive group and nerve invasion negative group (all P < 0.01); the differences in preoperative serum tPSA, PSAD, tumor diameter, and SUV max between patients with positive resection margins or not were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that the tumor resection margin status (negativity vs. positivity: HR = 7.82,95% CI: 1.97-31.07, P < 0.01), ISUP pathological grade (low grade vs. high grade: HR = 4.34,95% CI:1.21-15.62, P < 0.05), and the preoperative SUV max (<16.77 vs. ≥ 16.77: HR = 4.18, 95% CI:1.36-12.85 , P < 0.05) were independent influencing factors for RFS in patients with prostate cancer after radical prostatectomy. Conclusions:Pathological grading after radical prostatectomy and the preoperative 18F-PSMA-1007 PET/CT parameters are associated with the prognosis of patients with prostate cancer.
5.Clinical value of 18F-PSMA-1007 PET/CT combined with serum total prostate specific antigen in predicting International Society of Urological Pathology pathological grading of prostate cancer
Yunfeng BO ; Rongrong TIAN ; Lanlan BAO ; Ming ZHAO ; Jie ZHOU ; He LI ; Hailong HAO ; Enwei XU
Chinese Journal of Oncology 2025;47(2):175-182
Objective:To discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P<0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P<0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P<0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P<0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P<0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P<0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.
6.Differential analysis of coumarins in Angelica dahurica from different origins
Yingyu LIN ; Yingying YANG ; Enwei TIAN
China Pharmacy 2023;34(12):1422-1425
OBJECTIVE To screen the differential components of coumarins in Angelica dahurica from two origins (A. dahurica cv.‘ Hangbaizhi’; A. dahurica cv.‘ Qibaizhi’). METHODS Non-targeted metabolomics technique of UPLC-Q-Exactive- MS/MS was used to analyze the coumarins in 6 batches of A. dahurica cv. ‘Hangbaizhi’ and 12 batches of A. dahurica cv. ‘Qibaizhi’. The differential components were screened by principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. Cluster analysis was performed on differential components. RESULTS A total of 41 coumarins were identified in 18 batches of samples, in which 23 coumarins were differential components. Therein, 6 differential components were higher in content in A. dahurica cv.‘ Hangbaizhi’, while 17 differential components were higher in content in A. dahurica cv.‘ Qibaizhi’. The content of marmesin galactoside in A. dahurica cv.‘ Hangbaizhi’ was significantly higher than that in A. dahurica cv.‘ Qibaizhi’. Based on 23 differential components, A. dahurica cv.‘ Hangbaizhi’ and A. dahurica cv. ‘Qibaizhi’ could be grouped into one category, respectively. CONCLUSIONS The screened differential components of coumarins can be used to distinguish A. dahurica cv. ‘Hangbaizhi’ from A. dahurica cv. ‘Qibaizhi’, especially marmesin galactoside contributed the most, which can be used to identify A. dahurica cv.‘ Hangbaizhi’ and A. dahurica cv.‘ Qibaizhi’.
7.Establishment of the fingerprints for Danggui buxue pills and the method for the content determination of three indicative constituents
Jia’er FAN ; Yinrong LIU ; Zhi CHAO ; Enwei TIAN
China Pharmacy 2022;33(11):1343-1354
OBJECTIVE To establish the fingerprints of Danggui buxue pills a nd the method for the content determination of three indicative constituents (ferulic acid ,calycosin 7-O-β-D-glucoside and astragaloside Ⅳ). METHODS Fifteen batches of Danggui buxue pills from two manufacturers were analyzed by high performance liquid chromatography (HPLC). The determination was performed on a Hypersil ODS 2 C18 column with mobile phase consisted of acetonitrile- 0.2% formic acid (gradient elution )at the flow rate of 1.0 mL/min. The column temperature was set at 25 ℃,and the sample size was 20 μL. UV detector [detection wavelengths were 250 nm (calycosin 7-O-β-D-glucoside),323 nm (ferulic acid )] and evaporative light scattering detector (astragaloside Ⅳ)were selected as detectors. HPLC fingerprints of 15 batches of Danggui buxue pills were established with Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition). The chromatographic peaks were identified and assigned by comparing with the chromatogram of the reference substance and reference medicinal material ;the contents of ferulic acid ,calycosin 7-O-β-D-glucoside and astragaloside Ⅳ were also determined. RESULTS There were 33 common peaks in the fingerprints of 15 batches of samples with the similarities not lower than 0.893. Ferulic acid and calycosin 7-O-β-D-glucoside were identified as peak 13 and 15,respectively. Compared with the chromatogram of reference medicinal material,it could be found that peaks 1-3,7,8,10,12,13(ferulic acid ),17-19,27-29,32 and 33 belonged to Angelica sinensis,and peak 14,15(calycosin 7-O-β-D-glucoside),20-23,25 belonged to Astragalus membranaceus . The methodology of content determination met the requirements. The mean contents of ferulic acid ,calycosin 7-O-β-D-glucoside and astragaloside Ⅳ in 15 batches of samples were 0.050 1,0.402 6,0.913 4 mg/g. CONCLUSIONS In this study ,HPLC fingerprints of Danggui buxue pills and the method of HPLC quantitative analysis for three indicative constituents are established. Established methods are accurate,reliable and repeatable.
8.Correlation between RAS and BRAF V600E gene mutations and clinicopathological characteristics of colorectal cancer
Yunfeng BO ; Enwei XU ; Ning GAO ; Yanfeng XI ; Rongrong TIAN
Cancer Research and Clinic 2022;34(8):591-595
Objective:To investigate the correlation between KRAS, NRAS and BRAF V600E gene mutations and the clinicopathological characteristics of patients with colorectal cancer.Methods:Specimens from 217 patients with colorectal cancer who underwent surgical resection and were pathologically confirmed in Shanxi Province Cancer Hospital from January 2020 to December 2021 were selected, and the clinical data of the patients were retrospectively analyzed. The mutation status of KRAS, NRAS and BRAF V600E genes were detected in the paraffin specimens of surgically-resected tissues by direct sequencing. The mutation rates of KRAS, NRAS and BRAF V600E were compared among patients with different clinicopathological characteristics.Results:The mutation rates of KRAS, NRAS and BRAF V600E in 217 patients with colorectal cancer were 48.4% (105/217), 4.1% (9/217) and 3.7% (8/217), of which 1 patient (0.5%) had both KRAS and NRAS mutations. NRAS gene mutation was not correlated with gender, age, tumor size, tumor location, pathological type, degree of differentiation, depth of invasion, lymph node metastasis, distant metastasis, TNM stage, hemangioma thrombus/nerve invasion (all P>0.05); KRAS mutation rate in patients ≥ 60 year old was higher than that in patients < 60 year old [55.3% (63/114) vs. 40.8% (42/103), χ2 = 4.55, P = 0.033),and there was no correlation between KRAS gene mutation and other clinicopathological features (all P > 0.05); the mutation rate of BRAF V600E gene in colorectal cancerpatients with distant metastasis was higher than that in patients without distant metastasis [16.7% (4/24) vs. 2.1% (4/193), P = 0.006], and there was no correlation between BRAF V600E gene mutation and other clinicopathological features (all P > 0.05). Conclusions:Older colorectal cancer patients may be prone to KRAS gene mutation, and the BRAF V600E gene mutation rate is higher in patients with distant metastasis, and there is no correlation between NRAS gene mutation and clinicopathological characteristics.

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