1.Study on the Rule of Berberine Hydrochloride Through Carboxymethyl Chitosan-sodium Alginate Polyelectrolyte Hydrogel
Yujian WU ; Fanghao ZHENG ; Dongwen LIU ; Huaiguo LI ; Kaijun LEI ; Shiyu WANG
Chinese Journal of Modern Applied Pharmacy 2024;41(5):664-671
OBJECTIVE
To investigate the transfer and diffusion of berberine hydrochloride(BBH), the main active component of Coptis and Phellodenticum in the system of carboxymethyl chitosan(CMCS)-sodium alginate(SA).
METHODS
CMCS and SA were stirred in a certain proportion, and D-gluconolactone(GDL) was added to form polyelectrolyte hydrogel. Rheometer was used to study the rheological properties of CMCS-SA hydrogel, including the elastic modulus G′ and the viscous modulus G′′. A BBH diffusion model for CMCS-SA hydrogel was designed, and the relevant rules of BBH permeation through CMCS-SA polyelectrolyte hydrogel were observed by UV-VIS.
RESULTS
The elastic modulus G′ of the hydrogel was measured when the ratio of CMCS to SA was 3∶1, 2∶1, 1∶1, 1∶2, and 1∶3. When the ratio of CMCS to SA was 1∶1, G′ was the highest, and the crosslinking strength of the hydrogel was the highest. The cumulative amount of BBH transfer was measured by the BBH transfer model, and the diffusion of BBH in CMCS-SA hydrogel was fitted as the skeleton dissolution by Peppas equation, indicating that BBH dissociation and the transfer efficiency increased as the amino group of CMCS decreased or the carboxyl group of SA increased. The elastic modulus G′ of CMCS-SA hydrogel increased with the increase of GDL content. The reason was that the binding force between CMCS and SA molecules gradually increased with the decrease of pH, and the crosslinking degree of the hydrogel was enhanced. When ratio of fixed CMCS to SA was 1∶1 and the GDL content was 0.15 g·mL−1, the formability of CMCS-SA hydrogel was good. In addition, when BBH was transferred in hydrogel with different concentrations of GDL, the transfer efficiency increased with the increase of GDL content. When BBH was delivered in different thickness hydrogel, the delivery efficiency of CMCS-SA hydrogel increased with the decrease of thickness.
CONCLUSION
The CMCS-SA hydrogel system, as a potential drug carrier for traditional Chinese medicine extracts such as BBH, is expected to serve as a gel carrier for transdermal drug delivery.
2.Identification and study of regulatory axis that miRNA-224-5p targets NEDD4L gene in clear cell renal cell carcinoma
Yongquan CHEN ; Bo WU ; Yuan SHAO ; Weijing HU ; Lin ZHANG ; Dongwen WANG
Cancer Research and Clinic 2023;35(2):104-110
Objective:To screen key genes of renal clear cell carcinoma based on bioinformatics methods, identify possible microRNA (miRNA)-mRNA action axis, and explore the expression of related genes in clear cell renal cell carcinoma tissues and cells.Methods:Gene expression profiles of GSE40435 and GSE71302 datasets were obtained from the Gene Expression Omnibus (GEO) database. TCGA-KIRC datasets were obtained from The Cancer Genome Atlas (TCGA) database. R software was used to identify the differentially expressed mRNA and miRNA, and the functional enrichment analysis was performed. STRING database and Cytoscape software were used to perform the protein interaction analysis. The prognosis-related differentially expressed miRNA was evaluated by the Oncomir database. The potential targeted genes regulated by miRNA were determined by using TargetScan and miRDB targeted gene prediction tools. The tissue samples and clinicopathological features of 34 patients with clear cell renal cell carcinoma in the First Hospital of Shanxi Medical University from June to December 2021 were collected, and normal renal cell line 293T and clear cell renal cell carcinoma cell line 786O were selected. The real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), was used to detect the relative expression of genes; Western blotting and immunohistochemical staining were used to detect the expression levels of the targeted proteins. The dual luciferase reporter gene assay was carried out to verify the targeting relationship between genes.Results:A total of 1 351 differentially expressed mRNA and 50 differentially expressed miRNA were screened and identified. The result of functional enrichment analysis suggested that the fatty acid metabolism pathway and xenobiotic metabolism pathway were suppressed in clear cell renal cell carcinoma, while the apoptosis and immune response pathways were activated. Protein interaction analysis suggested that the signal transduction and protein ubiquitination pathways might play a key role in clear cell renal cell carcinoma. The screening results showed that miRNA-224-5p (miR-224-5p) was most closely associated with clear cell renal cell carcinoma progression and was highly expressed in tumor tissues, and its prognosis-related target gene was NEDD4L. The relative expression of NEDD4L mRNA in clear cell renal cell carcinoma tissues and paraneoplastic tissues were 0.138±0.103 and 1.000±0.026 ( t = 46.23, P < 0.05), and the relative expression of miR-224-5p was 1.000±0.043 and 0.129±0.108 ( t = 45.28, P < 0.05). The differences of NEDD4L mRNA and miR-224-5p expressions in different grades and stages of clear cell renal cell carcinoma tissues were statistically significant (all P < 0.05). The expression of NEDD4L protein was decreased in clear cell renal cell carcinoma. The relative expression of NEDD4L gene in 293T and 786O cells were 1.000±0.125 and 0.210±0.044 ( t = 17.52, P < 0.05); the relative expressions of miR-224-5p gene were 0.209±0.049 and 1.000±0.234 ( t = 10.61, P < 0.05). The relative expressions of NEDD4L mRNA in miRNA mimic group and negative control group were 0.236±0.062 and 1.000±0.024, and the difference was statistically significant ( t = 43.56, P < 0.05). NEDD4L protein expression was reduced in the miRNA mimic group. Dual luciferase reporter gene assay suggested that NEDD4L was a direct target gene of miR-224-5p. Conclusions:In clear cell renal cell carcinoma, miR-224-5p targets and regulates NEDD4L expression, and this mechanism may be related to carcinogenesis and progression of clear cell renal cell carcinoma.
3.Progress of cellular metabolism in renal cell carcinoma and its tumor microenvironment
Weijing HU ; Bo WU ; Dongwen WANG
Cancer Research and Clinic 2023;35(6):469-472
Renal cell carcinoma is one of the common tumors in the urinary system. Despite the high incidence of renal cell carcinoma worldwide, progress has been made in cancer control and patients' survival profits from advances in laparoscopic technology and the application of targeted drugs. Recent studies have confirmed that the progression of renal cell carcinoma is related to cellular metabolism in the tumor microenvironment. Therefore, based on the existing surgical treatment and immunotherapy, exploring new metabolic therapies that target the metabolic pathway of tumor cells and interfere with the microenvironment of tumor cells will provide a unique treatment for renal cell carcinoma.
4.Clinical value of a cuproptosis-related differential long non-coding RNA scoring formula in clear cell renal cell carcinoma
Yongquan CHEN ; Bo WU ; Weijing HU ; Xin WEI ; Lin ZHANG ; Dongwen WANG
Cancer Research and Clinic 2023;35(8):584-591
Objective:To investigate the value of a cuproptosis-related differential long non-coding RNA (lncRNA) scoring formula related to the prognosis of clear cell renal cell carcinoma (ccRCC) patients in the clinical diagnosis, prognosis prediction and treatment options based on bioinformatics.Methods:Gene matrix and clinical data of ccRCC patients were obtained from the Cancer Genome Atlas (TCGA) database (update to 29 March, 2022). The expression data of 539 ccRCC tissues and 72 paracancerous normal tissues were collected from gene matrix; the data of 530 ccRCC were collected from clinical data. Pearson correlation analysis, Wilcoxon signed rank test and univariate Cox proportional risk model were used to analyze the screened cuproptosis-related differential lncRNA related to the prognosis. R software was used to randomly divide 530 ccRCC patients with survival data into training set (266 cases) and validation set (264 cases) according to approximate 1∶1 ratio. LASSO regression analysis was used to construct a cuproptosis-related differential lncRNA scoring formula and cross-validation was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the specificity and sensitivity of cuproptosis-related differential lncRNA scoring formula, and the area of the curve (AUC) was calculated. According to the median risk value, all patients were divided into the low-risk group and high-risk group; Kaplan-Meier method was used to analyze the difference in the overall survival (OS) of patients in the low-risk group and high-risk group. T test was used to detect the differences in the risk value of patients with different clinicopathological characteristics. R package rms was used to construct the nomogram for predicting 1-year, 3-year, 5-year OS rates of ccRCC patients, R package pRRophetic was used to predict the half-inhibitory concentration ( IC50) of common targeted drugs such as sorafenib and sunitinib in clinical treatment of ccRCC patients, and IC50 value of patients in low-risk group and high-risk group was compared by using Wilcoxon signed rank test. Tissue samples of 20 ccRCC patients who underwent radical nephrectomy and were diagnosed with pathology and the matched paracancerous normal tissues were collected from the First Hospital of Shanxi Medical University between June 2021 and December 2021. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of key lncRNA in ccRCC tissues. Results:Based on the expression matrix of 10 cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, CDKN2A) of ccRCC patients in TCGA database, 153 cuproptosis-related differential lncRNA related to the prognosis were identified. According to LASSO regression analysis, a scoring formula of 4 cuproptosis-related differential lncRNA related to the prognosis was obtained, risk value was calculated as 0.020×AC015912.3+0.011×AC026401.3+0.063×AC103706.1+(-0.076)×EPB41L4A-DT. All patients were divided into high-risk group (≥0.76) and low-risk group (<0.76) based on the median value (0.76). ROC curve analysis showed that the scoring formula had good prediction accuracy in 1-year, 3-year, 5-year OS rates. In training set, validation set, the total cohort, the OS of patients in the high-risk group was worse than that in the low-risk group (all P < 0.001). The age, pathological degree, tumor staging, risk value calculated by cuproptosis-related differential lncRNA were independent influencing factors of OS (all P < 0.001). There were statistically significant differences in the risk value calculated by cuproptosis-related differential lncRNA scoring formula among patients with different pathological degree, tumor staging, T staging, N staging, M staging (all P < 0.01), while there were no statistically significant differences among patients with different gender and age (all P > 0.05). The established nomogram had good prediction accuracy in the 1-year, 3-year, 5-year OS rates. Sunitinib and sirolimus showed higher sensitivity in the high-risk group; axitinib, sorafenib and pazopanib showed higher sensitivity in the low-risk group. qRT-PCR results showed that relative expression level of AC015912.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.68±0.24, t = 6.37, P < 0.01); the relative expression level of AC026401.3 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.05 vs. 0.64±0.22, t = 7.29, P < 0.01); the relative expression level of AC103706.1 in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.04 vs. 0.64±0.21, t = 7.49, P < 0.01); the relative expression level of EPB41L4A-DT in ccRCC tissues was up-regulated compared with paracancerous tissues (1.00±0.06 vs. 0.73±0.10, t = 10.68, P < 0.01). Conclusions:Cuproptosis-related differential lncRNA scoring formula based on TCGA database can be used as a new marker for clinical diagnosis and prognosis prediction of ccRCC patients, which can help guide the clinical drug treatment of patients and facilitate accurate diagnosis and treatment.
5.Research advances on exosome miRNA in diabetic cystopathy
Bo XUE ; Libin SUN ; Bo WU ; Jinming TIAN ; Dongwen WANG
Chinese Journal of Geriatrics 2022;41(10):1254-1258
The pathogenesis of diabetic cystopathy(DCP)is complex and early diagnosis is hindered by a lack of specific and sensitive criteria and more research is needed to establish guidelines for its clinical diagnosis and treatment.Exosomes are membrane vesicles carrying various biological information such as proteins and nucleic acids, which are critical for communication between different tissues and organs.This review discusses the potential role of exosome miRNA in the pathogenesis of DCP and its application in therapy, aiming to provide new insight into the diagnosis and treatment of DCP.
6.Computational fluid dynamics study on the effects of morphology of prostatic urethra in mid-voiding after minimally invasive surgery with BPH
Bin ZHANG ; Shuang LIU ; Xuhui ZHANG ; Xuezhi LIANG ; Bo WU ; Rong LIU ; Xiaoming CAO ; Dongwen WANG
Chinese Journal of Urology 2021;42(3):226-228
It is important to investigate the mechanical effects of morphology of prostatic urethra (PU) for benign prostatic hyperplasia (BPH). PU and bladder neck transverse diameter ratio (RPU-1), which related to vortex, and their influence on urine flow were observed by CFD. The results showed that vortexes appeared and expanded with increasing RPU on both sides of PU when RPU-1>0.79, and velocity of external urethral orifice decreased gradually. CFD is an available method for urodynamics research. The quantitative simulation of the relationship between RPU-1 and vortex was proposed for the first time, providing a new idea for advancing theory of PU lumen repair in BPH.
7.Efficacy and safety study of Chinese botulinum toxin A 100U in patients with overactive bladder: a prospective, multicenter, double-blind and randomized controlled trial
Limin LIAO ; Huiling CONG ; Zhihui XU ; Enhui LI ; Zhiliang WENG ; Haihong JIANG ; Ben LIU ; Xiao HUANG ; Shujie XIA ; Wei WEN ; Juan WU ; Guowei SHI ; Yang WANG ; Peijun LI ; Yang YU ; Zujun FANG ; Jie ZHENG ; Ye TIAN ; Haodong SHANG ; Hanzhong LI ; Zhongming HUANG ; Liqun ZHOU ; Yunxiang XIAO ; Yaoguang ZHANG ; Jianlong WANG ; Xiaodong ZHANG ; Peng ZHANG ; Dongwen WANG ; Xuhui ZHANG ; Keji XIE ; Bin WANG ; Lulin MA ; Xiaojun TIAN ; Lijun CHEN ; Jinkai DONG
Chinese Journal of Urology 2021;42(6):414-422
Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.
8.The efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation: a randomized, controlled, multi-center clinical trial with 2 years’ follow-up
Hao YU ; Kaiwen LI ; Hailong HU ; Xiang LI ; Nan LIU ; Jian ZHANG ; Xudong YAO ; Xiaodong ZHANG ; Wei LI ; Liqun ZHOU ; Xiangbo KONG ; Jinjian YANG ; Youhan CAO ; Junli WEI ; Jiacun CHEN ; Zhaoyang WU ; Dongwen WANG ; Xuhui ZHANG ; Jinkai SHAO ; Qingwen LI ; Huiqing ZHANG ; Xiaolin WANG ; Shaozhong WEI ; Ye TIAN ; Tie ZHONG ; Hongshun MA ; Kun LI ; Benkang SHI ; Jin YANG ; Yuhua QIAO ; Hongxing HUANG ; Liming LI ; Zhimin WANG ; Jianhua TIAN ; Tianxin LIN ; Jian HUANG
Chinese Journal of Urology 2020;41(10):724-730
Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.
9.Single-center study of the abnormal concentration of bone imaging agent and prostate cancer bone metastasis prediction model
Yan CHENG ; Liping LUO ; Shan HU ; Lina LI ; Chen WU ; Bo WU ; Dongwen WANG
Chinese Journal of Oncology 2020;42(10):876-881
Objective:To investigate the relationship between total prostate specific antigen (TPSA), free prostate specific antigen/total prostate specific antigen [RAT (F/T)], Gleason score, other factors and the whole-body bone plane imaging which was used to evaluate the bone metastasis of prostate cancer (PCa), and the diagnostic value of the abnormal concentration of bone imaging agent for single lesion.Methods:A retrospective analysis of 99Tc m-methylene diphosphonate ( 99Tc m-MDP) whole-body bone imaging data of 93 patients with confirmed PCa in The First Hospital of Shanxi Medical University from Jan 2018 to Jan 2019 was conducted. The bone metastasis was diagnosed by whole-body bone imaging. The factors related to PCa bone metastasis, including age, TPSA, RAT (F/T), Gleason score were analyzed by Chi-square test and logistic two-class regression. The optimal cut-off point of TPSA was defined by receiver operating characteristic (ROC) curve. The region of interest (ROI) technique was used to repeatedly delineate the lesion (T) and the background area (NT) outside the bone and calculate the abnormal concentration value of bone imaging agent (T-NT)/NT, and the ROC curve was used to determine its diagnostic value. Results:The result of Chi-square analysis showed that Gleason score, TPSA and RAT (F/T) were associated with bone metastasis ( P<0.05). Logistic regression analysis showed that TPSA and RAT (F/T) were associated with bone metastasis ( P<0.01). TPSA >92.82 ng/ml was the best diagnosis for bone metastasis, and the sensitivity and specificity were 77.1% and 81.0%, respectively. There were 320 sites of high concentration of imaging agents in the whole-body bone imaging of PCa patients (194 in the metastatic group and 126 in the non-metastasis group). The (T-NT)/NT in the bone metastasis group was 7.11±0.29, the non-bone metastasis group was 2.69±0.20. (T-NT)/NT >3.52 was the best diagnosis for bone metastasis of single lesion, and the sensitivity and specificity were 86.1% and 80.2%, respectively. Conclusions:Gleason score, RAT (F/T) and TPSA are important risk factors of PCa bone metastasis. TPSA >92.82 ng/ml is the most supportive diagnosis for PCa bone metastasis. The abnormal concentration of bone imaging agent >3.52 owns the best diagnosis effect for the single lesion of PCa.
10.Single-center study of the abnormal concentration of bone imaging agent and prostate cancer bone metastasis prediction model
Yan CHENG ; Liping LUO ; Shan HU ; Lina LI ; Chen WU ; Bo WU ; Dongwen WANG
Chinese Journal of Oncology 2020;42(10):876-881
Objective:To investigate the relationship between total prostate specific antigen (TPSA), free prostate specific antigen/total prostate specific antigen [RAT (F/T)], Gleason score, other factors and the whole-body bone plane imaging which was used to evaluate the bone metastasis of prostate cancer (PCa), and the diagnostic value of the abnormal concentration of bone imaging agent for single lesion.Methods:A retrospective analysis of 99Tc m-methylene diphosphonate ( 99Tc m-MDP) whole-body bone imaging data of 93 patients with confirmed PCa in The First Hospital of Shanxi Medical University from Jan 2018 to Jan 2019 was conducted. The bone metastasis was diagnosed by whole-body bone imaging. The factors related to PCa bone metastasis, including age, TPSA, RAT (F/T), Gleason score were analyzed by Chi-square test and logistic two-class regression. The optimal cut-off point of TPSA was defined by receiver operating characteristic (ROC) curve. The region of interest (ROI) technique was used to repeatedly delineate the lesion (T) and the background area (NT) outside the bone and calculate the abnormal concentration value of bone imaging agent (T-NT)/NT, and the ROC curve was used to determine its diagnostic value. Results:The result of Chi-square analysis showed that Gleason score, TPSA and RAT (F/T) were associated with bone metastasis ( P<0.05). Logistic regression analysis showed that TPSA and RAT (F/T) were associated with bone metastasis ( P<0.01). TPSA >92.82 ng/ml was the best diagnosis for bone metastasis, and the sensitivity and specificity were 77.1% and 81.0%, respectively. There were 320 sites of high concentration of imaging agents in the whole-body bone imaging of PCa patients (194 in the metastatic group and 126 in the non-metastasis group). The (T-NT)/NT in the bone metastasis group was 7.11±0.29, the non-bone metastasis group was 2.69±0.20. (T-NT)/NT >3.52 was the best diagnosis for bone metastasis of single lesion, and the sensitivity and specificity were 86.1% and 80.2%, respectively. Conclusions:Gleason score, RAT (F/T) and TPSA are important risk factors of PCa bone metastasis. TPSA >92.82 ng/ml is the most supportive diagnosis for PCa bone metastasis. The abnormal concentration of bone imaging agent >3.52 owns the best diagnosis effect for the single lesion of PCa.


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