1.Mechanism of Shaoyaotang in Modulating MDSCs-related Immunosuppressive Microenvironment in Prevention and Treatment of Colitis-associated Carcinogenesis
Xue CHEN ; Chenglei WANG ; Bingwei YANG ; Haoyu ZHAI ; Ying WU ; Weidong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):10-19
ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis (CAC) based on myeloid-derived suppressor cells (MDSCs)-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups: Blank group, Shaoyaotang without model group (7.12 g·kg-1), model group, sulfasalazine group (0.52 g·kg-1), Shaoyaotang low-dose group (3.56 g·kg-1), Shaoyaotang medium-dose group (7.12 g·kg-1) and Shaoyaotang high-dose group (14.24 g·kg-1), with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline (10 mg·kg-1), while the other five groups were given a single intraperitoneal injection of azoxymethane (AOM) (10 mg·kg-1). After 1 week, the mice were given drinking water containing 2% dextran sulfate sodium (DSS) for 1 week, followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14th day of the experiment, followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28th and 98th days of the experiment. After dissection, the colon length, colon weight, spleen weight, tumor size, and tumor number were measured. Hematoxylin and eosin (HE) staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs, regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated nuclear factor-κB (p-NF-κB), and hypoxia-inducible factor 1α (HIF-1α) in the colon tissue. ResultsOn day 14, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01), reaching its lowest point on day 28 (23.39 ± 0.95 ) g. On days 28 and 98, compared with the blank group, the colon length in the model group was significantly shortened (P<0.01), the colon index significantly increased (P<0.01), the spleen index significantly increased (P<0.01), and the tumor load significantly increased (P<0.01). HE staining showed that in the model group, tumor cells, a large number of inflammatory cell infiltrates, goblet cell disappearance, and crypt loss were observed. In each dose group of Shaoyaotang, the damage to the colonic mucosa, inflammatory cell infiltration, and crypt structure destruction were alleviated. Compared with the model group, the body weight of mice in each dose group of Shaoyaotang increased. On day 98, the colon length was significantly increased (P<0.01), the colon index significantly decreased (P<0.01), the spleen index significantly decreased (P<0.01), and the tumor burden significantly decreased (P<0.01) in each Shaoyaotang dose group. On days 28 and 98, MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced (P<0.01), while CD4+ T cells and the CD4+/CD8+ T cell ratio were significantly increased (P<0.01). The proportion of CD8+ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees (P<0.05, P<0.01). On days 28 and 98, the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased (P<0.01), while the expression of p-NF-κB and HIF-1α was significantly reduced (P<0.01). ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.
2.Clinical Study on Treatment of Melasma Using Angelica and Safflower Spot Removal Essence Based on State-target Medicine
Bailin CHEN ; Haoyu YANG ; Rui CAI ; Yanping BAI ; Yuanyuan CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):111-119
ObjectiveTo investigate the clinical efficacy and safety of state-target formula Angelica and Safflower spot removal essence in the treatment of melasma. MethodsA randomized,double-blind,placebo-controlled parallel-group trial was conducted,selecting patients with Qi stagnation and blood stasis type of melasma who visited the dermatology outpatient department of Beijing Hospital of Integrated Traditional Chinese and Western Medicine from September 2022 to February 2023. In accordance with the double-blind principle,a random number table was generated to randomly divide the patients into an experimental group (50 cases) and a control group (50 cases). The experimental group applied the Angelica and Safflower spot removal essence topically,while the control group applied a placebo topically,with continuous treatment for 8 weeks and a follow-up of 1 month. Melasma Area and Severity Index (MASI),Physician Global Assessment (PGA),patient self-assessment scoring,VISIA detection and scoring were performed before medication and on the first day after stopping medication,and all adverse events were recorded. ResultsIn a study involving 100 patients,87 cases were included in the analysis. The experimental group consisted of 45 cases,with 5 dropouts,and the control group had 42 cases,with 8 dropouts. The baseline data of the patients in both groups were consistent,with no statistically significant differences. After treatment,the total effective rate of the experimental group was 75.56% (34/45),significantly higher than the control group's 2.38% (1/42),and the difference was statistically significant (χ2=48.38,P<0.01). Compared with before treatment,after treatment,the MASI score,VISIA image spot,brown spot,and red area score of the experimental group patients were significantly reduced (P<0.05,P<0.01),while there was no statistically significant difference in the control group patients. Compared with the control group after treatment,the experimental group showed more significant improvement (P<0.05,P<0.01). VISIA image analysis showed that after 8 weeks of treatment,the experimental group showed significant improvement in surface spots,deep spots,and red areas,while the control group remained unchanged or showed an increasing trend. 42.22% (19/45) of the experimental group had a PGA score of 3 or below,while 88.89% (40/45) had a PGA score of 4 or below. 80.95% (34/42) of the control group had a PGA score of 5 or above,and the difference between the two groups was statistically significant (χ2=38.26,P<0.01). There was no statistically significant difference in the recurrence rate and adverse reaction rate within one month between the experimental group and the control group. ConclusionThe state-target formula Angelica and Safflower spot removal essence is clinically effective and safe in the treatment of melasma.
3.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
4.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
5.Overview of the amendments and revisions to the General Technical Requirements adopted by the Volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition
ZHANG Jun ; NING Baoming ; WEI Shifeng ; SHEN Haoyu ; SHANG Yue ; ZHU Ran ; XU Xinyi ; CHEN Lei ; LIU Tingting ; MA Shuangcheng
Drug Standards of China 2025;26(1):034-044
To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines; further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly; replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.
6.Overview of the amendments and revisions to the General Technical Requirements adopted by the Volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition
Jun ZHANG ; Baoming NING ; Shifeng WEI ; Haoyu SHEN ; Yue SHANG ; Ran ZHU ; Xinyi XU ; Lei CHEN ; Tingting LIU ; Shuangcheng MA
Drug Standards of China 2025;26(1):34-44
To introduce the general thinking,guidelines,work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition,and to summarize and figure out the main characteristics on dosage forms,physico-chemical testing,microbial and biological testing,ref-erence standards and guidelines.The newly revised general chapters of pharmacopoeia give full play to the norma-tive and guiding role of the Chinese Pharmacopoeia standard,track the frontier dynamics of international drug regu-latory science and the elaboration of monographs,expand the application of state-of-the-art technologies,and stead-ily promote the harmonization and unification with the ICH guidelines;further enhance the overall capacity of TCM quality control,actively implement the 3 R principles on animal experiments,and practice the concept of environ-mental-friendly;replace and/orreduce the use of toxic and hazardousreagents,strengthen the requirementsofdrug safety control.This paper aims to provide a full-view perspective for the comprehensive,correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.
7.Development and validation of the Online Fraud Susceptibility Scale
Haoyu WANG ; Dan WANG ; Chen YANG
Chinese Mental Health Journal 2025;39(11):981-987
Objective:To develop and validate the Online Fraud Susceptibility Scale(OFSS).Methods:The construct of online fraud susceptibility was defined through qualitative interviews(n=14)and expert evaluations(n=6).Based on prior literature,an initial item pool was generated.A sample of 805 adults completed the preliminary scale for item analysis and exploratory factor analysis(EFA).Another sample of 491 adults completed the formal scale for confirmatory factor analysis(CFA),criterion validity,and internal consistency analysis.Of these,233 par-ticipants were retested after four months.The Vulnerability to Fraud Questionnaire(VFQ)and the Susceptibility to Persuasion-Ⅱ Scale(StP-Ⅱ)were used as criterion measures.Results:The 25-item OFSS consisted of 5 factors,na-rely monetary motivation,heuristic processing,financial risk-seeking,anti-fraud knowledge,and susceptibility to so-cial influence,explaining 51.94%of the total variance.The factor loadings ranged from 0.52 to 0.80.The 5-factor model showed an acceptable structural fit(x2/df=2.39,CFI=0.86,TLI=0.84,CFI=0.86,RMSEA=0.05).The OFSS scores were positively correlated with the scores of VFQ and StP-Ⅱ(r=0.51,0.47,Ps<0.001).The inter-nal consistency reliabilities of the total score and 5 factors ranged from 0.64 to 0.80,and the retest reliabilities(ICC)of the total score and 5 factors ranged from 0.53 to 0.78.Conclusion:The Online Fraud Susceptibility Scale demonstrates satisfactory psychometric properties providing a practical tool to assess the vulnerability to online fraud.
8.Smad3 signaling pathway promotes silica-induced epithelial-mesenchymal transition
Shiyu YANG ; Yingdie ZHANG ; Yujia XIE ; Haoyu YIN ; Pei GU ; Dongming WANG ; Weihong CHEN ; Jixuan MA
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(4):241-246
Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.
9.Relationship between membranous urethra length and early continence rate after robotic-assisted radical prostatectomy
Jinpeng SHAO ; Zhoujie YE ; Ziyan AN ; Jian ZHAO ; Haoyu ZOU ; Zongyu FU ; Kun ZHAO ; Xiaoxia CHEN ; Weijun FU
Chinese Journal of Urology 2025;46(2):104-109
Objective:To investigate the correlation between membranous urethral length (MUL) and early urinary continence recovery after robot-assisted radical prostatectomy (RARP).Methods:A retrospective analysis was conducted on 71 prostate cancer patients who underwent RARP by a single surgeon at the PLA General Hospital between January 2020 and December 2023. Patient characteristics included: age of (65.32±6.04) years, BMI (25.21 ± 2.59) kg/m 2, prostate volume 32.41 (24.75, 44.40) ml, PSA 11.67 (8.22, 22.66) ng/ml. Gleason score [6/7/8/9-10: 15 (21.2%)/29 (40.8%)/16 (22.5%)/11 (15.5%)], Clinical stage [cT 1/cT 2/cT 3: 4 (5.6%)/61 (85.9%)/6 (8.5%)]. Measured MUL using multiparametric prostate MRI, median MUL was 13.25 (10.41-14.99) mm. Neurovascular bundle (NVB) preservation in 13 (18.3%) cases. Patients were grouped based on continence recovery at 1 and 3 months post-catheter removal. Age, BMI, prostate volume, PSA, Gleason score, clinical stage, NVB preservation, pathological stage, catheter indwelling time, and MUL were compared between groups. Multivariate analysis identified independent predictors of continence recovery. Results:All 71 surgeries were successful, pathological stage [pT 2/pT 3-4: 47 (66.2%)/24 (33.8%)], and catheter indwelling time 2.7 (2.0, 3.0) weeks. Follow-up data at 2 months were available for 71 patients, at 1 month, 42 patients achieved continence (continence group) and 29 had incontinence (incontinence group).No significant differences were observed between continence and incontinence groups in age [(64.93±6.48)years vs. (65.79±5.89) years], BMI [(26.26±2.52)kg/m 2 vs. (24.52±2.42) kg/m 2], prostate volume [32.00 (24.12, 41.11)ml vs. 33.00 (25.27, 47.97) ml], PSA [12.55 (8.31, 24.00) ng/ml vs. 11.30 (7.92, 20.65) ng/ml], Gleason score [6/7/8/9-10: 6 (14.2%)/18 (42.9%)/12 (28.6%)/6 (14.3%) vs. 9 (31.0%)/11 (37.9%)/4 (13.8%)/5 (17.3%)], clinical stage [cT 1/cT 2/cT 3: 2 (4.8%)/35 (83.3%)/5 (11.9%) vs. 2 (6.9%)/26 (89.7%)/1 (3.4%)], NVB preservation [7 (16.7%) vs. 6 (20.7%)], pathological stage [pT 2/pT 3-4: 27 (64.3%)/15 (35.7%) vs. 20 (69.0%)/9 (31.0%)], or catheter indwelling time [2.6(2.0, 3.0) weeks vs. 2.9 (2.0, 3.4) weeks]. However, MUL was significantly longer in the continence group [13.77 (11.70, 15.32) mm vs. 10.32 (9.65, 13.57) mm, P<0.01]. Follow-up data at 3 months were available for 69 patients, At 3 months, 61 patients achieved continence (continence group) and 8 remained incontinent (incontinence group). No significant differences were observed in age [(64.89±6.25)years vs. (68.13±4.09) years], BMI [(25.34±2.64)kg/m 2 vs. (24.36±2.49) kg/m 2], prostate volume [32.41 (24.44, 44.16)ml vs. 36.13 (27.48, 48.26) ml], PSA [12.50 (8.28, 22.76)ng/ml vs. 13.34 (5.88, 23.39) ng/ml], Gleason score [6/7/8/9-10: 12 (19.7%)/25 (41.0%)/14 (23.0%)/10 (16.3%) vs. 3 (37.5%)/3 (37.5%)/2 (25.0%)/0], clinical stage [cT 1/cT 2/cT 3: 3 (4.9%)/52 (85.2%)/6 (9.8%) vs. 1 (12.5%)/7 (87.5%)/0], NVB preservation [9 (14.8%) vs. 3 (37.5%)], pathological stage [pT 2/pT 3-4: 41 (67.2%)/20 (32.8%) vs. 5 (62.5%)/9 (31.0%)], or catheter indwelling time [2.7(2.0, 3.0)weeks vs. 3.0 (2.3, 3.7) weeks]. MUL remained significantly longer in the continence group [13.57 (10.57, 15.10)mm vs. 10.12 (9.36, 10.42) mm, P=0.002]. Multivariate logistic regression incorporating age, BMI, prostate volume, MUL, NVB preservation, and catheter indwelling time identified MUL as an independent protective factor for continence recovery at both 1 month [ OR=0.62, 95 CI 0.49-0.79, P<0.01] and 3 months [ OR=0.61, 95 CI 0.41-0.92, P=0.017]. Conclusions:MUL is independently associated with early urinary continence recovery after RARP, serving as a protective predictor at both 1 and 3 months after catheter removal.
10.Predictive value of the percentage of Gleason pattern 4 in biopsy for adverse pathological features and biochemical recurrence after radical prostatectomy in ISUP grade group 2-3 non-metastatic prostate cancer
Haoyu WU ; Tianyu XIONG ; Yanning ZHANG ; Yunpeng FAN ; Tianyu ZHANG ; Zhanliang LIU ; Song JIN ; Guangyong CHEN ; Ping XIE ; Yinong NIU
Chinese Journal of Urology 2025;46(4):267-274
Objective:To assess the predictive value of the percentage of Gleason pattern 4 (G4%) in prostate biopsy for adverse pathology and biochemical recurrence.Methods:We retrospectively analyzed consecutive patients who underwent radical prostatectomy in our institution between January 2019 and December 2023, and included those who were diagnosed with ISUP 2-3 cancer at biopsy. A total of 109 patients were included in this study. The average age of patients was (67.40±6.11) years, and the average BMI of patients was (25.36±2.97) kg/m 2. 49 Cases (45.0%) had a PI-RADS score of 5, and the median prostate volume was 32.60 (24.57, 45.63) ml. The median of most recent tPSA before biopsy was 9.76 (6.89, 12.95) ng/ml, the median PSAD was 0.28 (0.17, 0.44) ng/ml 2, and the median f/tPSA was 0.11 (0.08, 0.16). Clinical T 2b or higher stage was found in 84 cases (77.1%). The total biopsy core length was (22.91±5.18) cm, with a median of 24 (20, 24) biopsy cores and a median of 6 (4, 9) positive cores. Gleason score 3+ 4 was found in 52 cases (47.7%), and Gleason score 4+ 3 in 57 cases (52.3%). Cribriform was present in 30 cases (27.5%). G4% was calculated based on the proportion of Gleason grade 4 tumor relative to total tumor, tumor proportion relative to total tissue, and tissue length. Patients were divided into high-G4% (≥2.45%) and low-G4% (<2.45%) groups based on the median G4% value, with 55 and 54 cases, respectively. No significant differences were observed in baseline characteristics between the two groups ( P>0.05). The main risk factor of adverse pathology was analyzed by logistic regression, and receiver operating characteristic (ROC) curve and area under curve (AUC) were performed. Patients were further stratified by the G4% cutoff value from ROC, and Kaplan-Meier survival curves were plotted to compare biochemical recurrence free survival (BCRFS) between groups. The main risk factor affecting BCRFS was analyzed by Cox regression. Adverse pathology was defined as postoperative Gleason score ≥4+ 3 or pathological stage ≥T 3a. Results:Adverse pathology occurred in 44 (80.0%) high-G4% and 16 (29.6%) low-G4% patients ( P<0.01). Multivariate analysis identified G4% as an independent risk factor for adverse pathology ( OR=1.23, 95% CI 1.02-1.50, P=0.033). The highest ROC AUC value was seen for G4% (0.799), significantly outperforming Gleason score (0.799 vs. 0.641, P=0.003), tPSA (0.799 vs. 0.615, P=0.003), PSAD (0.799 vs. 0.679, P=0.038), positive cores (0.799 vs. 0.677, P=0.009), clinical T stage (0.799 vs. 0.607, P=0.001) and cribriform (0.799 vs. 0.639, P=0.001). The G4% cutoff value for predicting biochemical recurrence was 10.97%. The median BCRFS was significantly higher in the low G4% (<10.97%) group than that in the high G4% (≥10.97%) group (55 vs. 28 months, P=0.002). Cumulative recurrence free survival rates at 1 and 3 years were 94.6% vs. 74.1% and 78.0% vs. 47.6%, respectively. Multivariate Cox regression analysis indicates that G4% was an independent risk factor affecting BCRFS ( HR=1.11, 95% CI 1.00-1.23, P=0.041). Conclusions:For patients with ISUP 2-3 nmPCa, a higher G4% in biopsy specimens demonstrates strong predictive ability for adverse pathology and biochemical recurrence, outperforming traditional clinical indicators such as Gleason score and PSA.

Result Analysis
Print
Save
E-mail