1.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
2.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
3.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
4.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
5.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
6.Impact of the number of microsatellite markers on the analysis of population genetic diversity of Schistosoma japonicum
Juan LONG ; Lang MA ; Hongying ZONG ; Zhipeng ZHOU ; Hao YAN ; Qinping ZHAO
Chinese Journal of Schistosomiasis Control 2025;37(3):239-246
Objective To examine the impact of different numbers of microsatellite markers on the analysis of population genetic diversity of Schistosoma japonicum, so as to provide insights into studies on the population genetic diversity of S. japonicum. Methods Oncomelania hupensis snails were collected from a wasteland in Gong’an County, Hubei Province, and 37 S. japonicum-infected O. hupensis snails were identified using the cercarial shedding method. A single cercaria released from each S. japonicum-infected O. hupensis snail was collected, and 10 cercariae were randomly collected from DNA extraction. Nine previously validated microsatellite loci and 15 additional microsatellite loci screened from literature review and the GenBank database and confirmed with stable amplification efficiency were selected as molecular markers. Genomic DNA from cercariae was subjected to three multiplex PCR amplifications of microsatellite markers with the Type-it Microsatellite PCR kit, and genotyped using capillary electrophoresis. The population genetic diversity of S. japonicum cercariae DNA was analyzed with observed number of alleles (Na), effective number of alleles (Ae), observed heterozygosity (Ho), expected heterozygosity (He), and polymorphism information content (PIC), and tested for Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD). To further investigate the impact of the number of microsatellite loci on the population genetic diversity of S. japonicum, the number of microsatellite markers was sequentially assigned from 1 to 24, and the mean and standard deviation of Na were calculated for S. japonicum populations at different locus numbers. In addition, the coefficient of variation (CV) of allelic number (defined as the ratio of the standard deviation to the mean) was determined, and the variation in Na with increasing microsatellite locus numbers was analyzed. Results Genomic DNA from 345 S. japonicum cercariae was selected for genotyping of 24 microsatellite markers, and all 24 microsatellite loci met linkage equilibrium (standardized linkage disequilibrium coefficient D′ < 0.7, r2 < 0.3) and deviated from Hardy-Weinberg equilibrium (P < 0.001). The mean Na, Ae, Ho and He were 27.46 ± 2.18, 12.46 ± 0.95, 0.46 ± 0.03, and 0.91 ± 0.01 for 24 microsatellite loci in S. japonicum cercarial populations, respectively, and PIC ranged from 0.85 to 0.96, indicating high genome-wide representativeness of 24 microsatellite loci. The mean value of Na-Ae was higher in genotyping with 9 previously validated microsatellite loci (19.88 ± 8.43) than with all 24 loci (14.99 ± 8.09). As the number of microsatellite loci increased, the mean Na showed no significant variation; however, the standard deviation gradually decreased. Notably, if the locus number reached 18 or more, the variation in the standard deviation of Na remarkably reduced. In addition, the standard deviation of Na at 18 loci was less than 5% of the mean Na at 24 loci, with a CV of 4.6%. Conclusions The number of microsatellite loci significantly affects the population genetic diversity analysis of S. japonicum. Eighteen or more microsatellite loci are recommended for analysis of the population genetic diversity of S. japonicum under the current conditions of low-prevalence infection and unbalanced genetic distribution of S. japonicum.
7.Effect of Longmu Piyan Prescription on Oxidative Stress in Atopic Dermatitis Mice
Mengxi MA ; Siqi WU ; Qingying WANG ; Yaqin LI ; Jinhe WANG ; Na LANG ; Jianxun REN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):88-95
ObjectiveThis study observes the intervention effect of Longmu Piyan prescription on oxidative stress in BALB/c mice with atopic dermatitis (AD) induced by 2,4-dinitrochlorobenzene (DNCB) and explores its mechanism. MethodThe AD model was established using the method of DNCB sensitization on the back skin of BALB/c mice. Forty male BALB/c mice were randomly divided into a blank group, a model group, a vitamin C control group (0.5×10-3 mg·kg-1), and a Longmu Piyan prescription group (26 g·kg-1). Except for the blank group, other groups were sensitized with different concentrations of DNCB on the back to induce AD, and the blank group was treated with matrix coating. The gastric administration was started on the seventh day after sensitization with 2% DNCB and on the 24th day after sensitization with 0.2% DNCB continuously for 21 days. The changes in skin lesions of each group were directly observed after the experiment. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)-4, tumor necrosis factor (TNF)-α, immunoglobulin E (IgE), and reactive oxygen species (ROS) in the serum of each group. The total antioxidant capacity determination kit-trace method (ABTS method) was used to measure the level of total antioxidant capacity (TAOC) in serum. The Hematoxylin eosin (HE) staining method was used to observe the pathological and morphological changes of the skin lesion site. The immunohistochemical method was used to detect the expression of thymic stromal lymphopoietin (TSLP) in the skin lesion site. Western blot was used to detect the expression of filaggrin (FLG) in the dorsal skin lesions. ResultThe results showed that compared with the blank group, the skin lesion score of the model group mice was significantly increased (P<0.01), and HE staining showed characteristic pathological changes of AD in the skin lesion site. At the same time, the expression of TSLP in the skin lesion was significantly increased, and that of FLG was reduced (P<0.05). The levels of TNF-α, IL-4, IgE, and ROS in serum increased, while the activity of TAOC decreased (P<0.01). Compared with the model group, the Longmu Piyan prescription group showed a significant decrease in skin lesion scores and a significant improvement in skin lesion pathology. At the same time, the expression of TSLP decreased, and the expression of FLG increased in the skin lesions (P<0.05). In addition, compared with the model group, the serum levels of TNF-α, IL-4, IgE, and ROS also decreased to varying degrees (P<0.05,P<0.01), and TAOC activity increased in the Longmu Piyan prescription group (P<0.01). ConclusionThere is a significant correlation among the degree of oxidative stress, the severity of skin lesions in AD, and the levels of inflammatory cytokines. Longmu Piyandu prescription can improve AD-like skin lesions in BALB/c mice by promoting ROS clearance, enhancing TAOC, and inhibiting oxidative stress, thus protecting the skin barrier and reducing inflammation.
8.The hemostatic effect and its mechanism of modified Sijunzi Decoction on the zebrafish intestinal bleeding model through 5-hydroxytryptamine and its receptors
Jun WANG ; Haiyan LANG ; Jiali ZHOU ; Xueying ZHANG ; Yanhong KANG ; Yun ZHANG ; Xinyi CHEN ; Wei MA
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):516-522
Objective We aimed to investigate the hemostatic effect and mechanism of modified Sijunzi Decoction(MSJZT),consisting of tangshen,India bread,largehead atractylodes rhizome,liquorice root,milkvetch root,ass hide glue,and India madder root,on the zebrafish intestinal bleeding model through 5-hydroxytryptamine(5-HT)and its receptors(5-HT2aR,5-HT2bR).Methods Zebrafish at 4 days post fertilization were used as the research object.An intestinal bleeding model was established by induction with 6 μmol/L simvastatin for 24 hours.The zebrafish were divided into normal group,model group,MSJZT low-,mid-and high-concentration groups(55.6,167,500 mg/L),and after modeling,the corresponding concentration of MSJZT was administered.The samples were collected after 24 hours.Platelet count(PLT)and bleeding status were observed.The content of 5-HT and Caspase 3/7 activity were detected by colorimetry.The gene expressions of 5-HT2aR,5-HT2bR and serotonin transporter(SERT)were detected by real-time PCR.The protein expressions of protein kinase B(AKT),phosphorylated AKT(p-AKT),extracellular signal-regulated protein kinase(ERK),and phosphorylated ERK(p-ERK)were detected by Western blotting.Results The intestinal bleeding rate in the model group was 70.0%,and that in the MSJZT low-,mid-and high-concentration groups was 36.7%,40.0%,and 80.0%,respectively;the intestinal hemostatic effect was 54%,52%,and 7%,respectively.Compared with the model group,the PLT in the MSJZT low-and mid-concentration groups decreased;the content of 5-HT in all MSJZT groups increased,and the gene expressions of 5-HT2aR and 5-HT2bR were up-regulated.The gene expression of SERT was up-regulated in the low-and mid-concentration groups;the Caspase 3/7 activity in the mid-and high-concentration groups was reduced;the expressions of p-AKT and p-ERK proteins were up-regulated in the low-and mid-concentration groups(all P<0.05).Conclusion MSJZT can reduce the incidence and severity of intestinal bleeding in zebrafish intestinal bleeding models.The mechanism may be achieved by activating AKT and ERK signaling pathways through 5-HT and its receptors.
9.Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway
Chaodi SUN ; Mengmeng ZHAO ; Xiaomeng LANG ; Jie REN ; Xin KANG ; Jiancong CUI ; Sujie JIA ; Yujing MA ; Yue LIU ; Qiang CHUAI ; Wenjing ZHAI ; Jianping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):174-182
ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA). ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.
10.Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride
Lang ZHOU ; Ke LIU ; Min LU ; Hai BI ; Xiao HUO ; Lulin MA ; Cheng LIU
Journal of Modern Urology 2024;29(2):101-107
【Objective】 To explore the effects of finasteride on the gene expression in patients with benign prostatic hyperplasia (BPH) through transcriptome analysis. 【Methods】 Postoperative prostate tissues from patients who underwent prostatectomy at Peking University Third Hospital during Oct.2020 and Oct.2021 were collected.The patients were divided into medication group and non-medication group based on whether they had taken finasteride for a long time before surgery, with 8 patients in either groups.Transcriptome sequencing analysis was performed and the results were validated with qPCR and immunohistochemistry analysis. 【Results】 Compared with the non-medication group, 857 up-regulated and 806 down-regulated genes were screened in the medication group.Pathway enrichment analysis showed that finasteride induced down-regulation of vascular endothelial growth factor D (VEGFD) expression in the focal adhesion pathway.Inter group network analysis suggested that the calcium signaling pathway was key in the entire process.GSEA enrichment analysis further revealed the up regulation of CD38 gene expression in the calcium signaling pathway.The qPCR and immunohistochemistry analysis supported the transcriptome results mentioned above, and found that androgen receptor (AR) expression was also increased. 【Conclusion】 Finasteride reduces prostate microvascular formation by downregulating the expression of VEGFD in the focal adhesion pathway, thereby reducing the risk of bleeding during prostate hyperplasia surgery. Long-term use of finasteride leads to the up regulation of CD38 expression in the calcium signaling pathway, which may lead to the development of finasteride resistance.

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