1.Influence of curative-intent resection with textbook outcomes on long-term prognosis of gall-bladder carcinoma: a national multicenter study
Zhipeng LIU ; Zimu LI ; Yule LUO ; Xiaolin ZHAO ; Jie BAI ; Yan JIANG ; Yunfeng LI ; Chao YU ; Fan HUANG ; Zhaoping WU ; Jinxue ZHOU ; Dalong YIN ; Rui DING ; Wei GUO ; Yi ZHU ; Wei CHEN ; Kecan LIN ; Ping YUE ; Yao CHENG ; Haisu DAI ; Dong ZHANG ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2024;23(7):926-933
Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.
2.Applications and recent advances in transdermal drug delivery systems for the treatment of rheumatoid arthritis.
Yuyi XU ; Ming ZHAO ; Jinxue CAO ; Ting FANG ; Jian ZHANG ; Yanli ZHEN ; Fangling WU ; Xiaohui YU ; Yaming LIU ; Ji LI ; Dongkai WANG
Acta Pharmaceutica Sinica B 2023;13(11):4417-4441
Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.
3.Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study
Zhipeng LIU ; Xuelei LI ; Haisu DAI ; Weiyue CHEN ; Yuhan XIA ; Wei WANG ; Xianghao YE ; Zhihua LONG ; Yi ZHU ; Fan HUANG ; Chao YU ; Zhaoping WU ; Jinxue ZHOU ; Dong ZHANG ; Rui DING ; Wei CHEN ; Kecan LIN ; Yao CHENG ; Ping YUE ; Yunfeng LI ; Tian YANG ; Jie BAI ; Yan JIANG ; Wei GUO ; Dalong YIN ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2023;22(7):866-872
Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.
4.A modified Blumgart procedure in laparoscopic pancreaticoduodenectomy
Minghao GOU ; Zhengzheng WANG ; Binyang JIA ; Nanmu YANG ; Qingjun LI ; Haitao ZHAO ; Jinxue ZHOU
Chinese Journal of General Surgery 2023;38(1):12-16
Objective:To evaluate A modified Blumgart pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 81 patients undergoing laparoscopic pancreaticoduodenectomy in Zhengzhou University Affiliated Cancer Hospital from Jan 2019 to Jan 2022 were retrospectively analyzed. Among them, 26 patients underwent modified Blumgart anastomosis and 55 underwent conventional Blumgart anastomosis.The data of demographics, liver function, pancreatic texture, operational result and complications were compared between the two groups.Results:The preoperative data (body mass index, preoperative albumin, prealbumin, transaminase, total bilirubin) between two groups were comparable ( P>0.05). There was no significant difference in pancreatic texture, pancreatic duct diameter and intraoperative blood loss between the two groups ( P>0.05). The modified group had shorter total operation time ( P<0.05), shorter pancreaticojejunostomy time ( P<0.05), shorter postoperative hospital stay ( P<0.05). The incidence of total pancreatic fistula and biochemical fistula in the modified group were lower than those in the conventional group ( P<0.05). There was no significant difference in the incidence of B/C grade pancreatic fistula and bile leakage, postoperative bleeding, infection and delayed gastric emptying between the two groups ( P>0.05). Conlusions:The modified Blumgart pancreaticojejunostomy during laparoscopic pancreaticoduodenectomy is safe, easy to do and time saving. While the incidence of postoperative pancreatic fistula with clinical significance and other major complications were similar to traditional Blumgart procedure.
5.A retrospective comparative study on a new cold-circulation bipolar radiofrequency assisted versus Habib-4x bipolar radiofrequency assisted open hemihepatectomy
Zhengzheng WANG ; Jingzhong OUYANG ; Minghao GOU ; Yanzhao ZHOU ; Qingjun LI ; Nanmu YANG ; Jinxue ZHOU
Chinese Journal of Hepatobiliary Surgery 2021;27(11):806-809
Objective:To compare the clinical outcomes between the new cold-circulation bipolar radiofrequency assisted versus Habib-4X bipolar radiofrequency assisted open hemihepatectomy.Methods:A retrospective study was conducted on 45 patients who underwent bipolar radiofrequency assisted open hemihepatectomy at the Affiliated Tumor Hospital of Zhengzhou University from October 2016 to January 2020. There were 28 males and 17 females, with an average age of 52.2 years. These patients were divided into the experimental group ( n=20) who underwent the new cold-circulation bipolar radiofrequency assisted open liver resection, and the control group ( n=25) who underwent the Habib 4X bipolar radiofrequency assisted open liver resection. The postoperative alanine aminotransferase (ALT), postoperative aspartate aminotransferase (AST), liver coagulative necrosis plane width, speed of liver parenchymal transection, electrode needle carbonization rate, and postoperative complications were compared between groups. Results:In the experimental group, the speed of liver parenchymal transection was (5.0±2.0) cm 2/min, the width of the coagulative necrosis plane was (1.36±0.21) cm, the AST on the first postoperative day was (177.0±79.3) U/L, the ALT on the first postoperative day was (200.2±78.5) U/L, and the electrode needle tip carbonization rate was 20.0% (4/20). These figures were significantly better than the control group with (3.6±1.7) cm 2/min, (1.93±0.16) cm, (233.2±66.6) U/L, (249.2±62.9) U/L, and 56.0% (14/25), respectively (all P<0.05). The postoperative complication rate was 15.0% (3/20) in the experimental group and 24.0% (6/25) in the control group ( P>0.05). Conclusion:Cold-circulation bipolar radiofrequency assisted hemihepatectomy was safe and feasible. It had the advantages of rapid transection of liver parenchyma, a low electrode tip carbonization rate, and a more accurate coagulation range.
6.Clinical application on laparoscopic liver tumor resection in children
Qingjun LI ; Xun CHEN ; Nanmu YANG ; Zhengzheng WANG ; Xiangyu ZHAN ; Ruili ZHU ; Yanzhao ZHOU ; Feng HAN ; Jinxue ZHOU
Chinese Journal of Applied Clinical Pediatrics 2021;36(7):537-539
Objective:To investigate the feasibility and safety of laparoscopic liver tumor resection in children.Methods:The clinical data of 6 children undergoing laparoscopic liver tumor resection from June 2018 to March 2020 in the Affiliated Tumor Hospital, Zhengzhou University were retrospectively analyzed.Results:There were 4 males and 2 females among the 6 cases, with the average age of (7±2)years.All the children were admitted to the hospital with a liver occupying examination due to physical discomfort.Preoperative diagnosis: 3 cases of hepatoblastoma, 1 case of primary liver cancer, 1 case of hepatic adenoma and 1 case of hepatic nodular hyperplasia.All the children successfully completed laparoscopic liver tumor resection without conversion to open surgery.Among them, 3 children obtained left hemihepatectomy, 1 child underwent hepatic left lobectomy, 1 child was given VI hepatectomy, and 1 child accepted hepatic caudate lobectomy.The operation time was(90±9)min, and the average intraoperative blood loss was (83±26) mL.All children had no blood transfusion during or after operation.There were no bleeding, bile leakage, infection and liver failure after operation.All children had no gastric tube before surgery and the fluid diet was given on the first day after operation, and the postoperative median hospital stay was 4(3-5) days.The pathology were consis-tent with the preoperative diagnosis, and the resections were all radical operation resections.The follow-up period was from 2 to 23 months, and all the children recovered well and no recurrence was observed.Conclusions:Laparoscopic liver tumor resection in children is safe and feasible, which can minimize trauma, reduce intraoperative bleeding and shorten the hospital stay without increasing the incidence of postoperative complications.Laparoscopic liver tumor resection in children has certain advantages.
7.Application of combined therapy with molecular-targeted drugs and immune checkpoint inhibitors and other combined therapies in hepatocellular carcinoma
Jingzhong OUYANG ; Yanzhao ZHOU ; Ruili ZHU ; Zhengzheng WANG ; Xun CHEN ; Jinxue ZHOU ; Qingjun LI
Journal of Clinical Hepatology 2021;37(4):925-930
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its features of insidious onset, rapid development, and high recurrence bring great challenges to the long-term survival of HCC patients. Molecular-targeted drugs and immune checkpoint inhibitors have become the research hotspots in the treatment of HCC, and a large number of clinical trials have found that combined therapy has achieved a good clinical effect. This article mainly introduces the application of combined therapy with molecular-targeted drugs and immune checkpoint inhibitors and other combined therapies in HCC and points out that combined therapy related to systemic therapy or local therapy has become the latest research hotspot in HCC treatment.
8.Application value of a new internal cold circulation bipolar radio frequency device in open hepatectomy
Yanzhao ZHOU ; Zhengzheng WANG ; Xun CHEN ; Ruili ZHU ; Jingzhong OUYANG ; Qingjun LI ; Hao ZHUANG ; Jinxue ZHOU
Chinese Journal of Digestive Surgery 2021;20(8):898-905
Objective:To investigate the application value of a new internal cold circula-tion bipolar radio frequency device in open hepatectomy.Methods:The retrospective cohort study was conducted. The clinical data of 85 patients with hepatocellular carcinoma who underwent open hepatectomy at the Affiliated Tumor Hospital of Zhengzhou University from February 2017 to January 2020 were collected. There were 48 males and 37 females, aged from 32 to 74 years, with a median age of 52 years. Of 85 patients, 45 cases undergoing hepatectomy assisted by the new internal cold circulation bipolar radio frequency device were allocated into new internal cold circulation bipolar radio frequency device group, and 40 cases undergoing hepatectomy assisted by Habib-4X bipolar radio frequency device were allocated into Habib-4X group, respectively. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient, inpatient reexamination and telephone interview to detect the postoperative complications and death of patient within postoperative 30 days up to May 2020. Measurement data with normal distribution were represented as Mean± SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and nonparametric Mann-Whitney U test was used for comparison between groups. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Repeated measurement data were anlyzed by the repeated ANOVA. Results:(1) Intraoperative situations: the time of crosscutting process for liver parenchyma, average area transection speed, coagulation tissue width, cases with needle bleeding rate and electrode needle charring were (55±16)minutes, (4.8±1.2)cm 2/minute, (1.4±0.2)cm, 6, 10 for the new internal cold circulation bipolar radio frequency device group, versus (64±15)minutes, (3.6±1.0)cm 2/minute, (1.8±0.2)cm, 14, 25 for the Habib-4X group, respectively, showing significant differences in the above indicators between the two groups ( t=2.665, 4.973, 9.204, χ2=5.525, 14.184, P<0.05). (2) Postoperative situations: for the new internal cold circulation bipolar radio frequency device group, the total bilirubin (TBil) was (20±12)μmol/L, (25±12)μmol/L, (20±14)μmol/L at postoperative 1, 3, 7 days, the prothrombin time (PT) was (15.4±2.2)seconds, (14.2±2.1)seconds, (12.7±0.8)seconds, the alanine aminotransferase (ALT) was (288±248)IU/L, (132±61)IU/L, (67±32)IU/L, the aspartate aminotransferase (AST) was (279±114)IU/L, (50±22)IU/L, (30±13)IU/L. For the Habib-4X group, the TBil was 1(22±15)μmol/L, (23±10)μmol/L, (19±8)μmol/L at postoperative 1, 3, 7 days, PT was (15.8±2.8)seconds, (14.3±2.0)seconds, (13.6±1.3)seconds, the ALT was (369±269)IU/L, (133±99)IU/L, (54±30)IU/L, the AST was (345±125)IU/L, (60±36)IU/L, (32±11)IU/L. There were significant differences in the time effect of PT, ALT, AST between the two groups ( F=18.364, 23.020, 93.786, P<0.05). There was no significant difference in the time effect, between-group effect, interaction effect of TBil or between-group effect, interaction effect of PT, ALT, AST between the two groups ( F=2.421, 1.424, 0.522, 1.593, 0.312, 0.121, 0.267, 1.027, 0.600, P>0.05). (3) Follow-up: 85 patients were followed up for 4 to 39 months, with a median follow-up time of 16 months. There were 5 patients in the new internal cooling circulation bipolar radiofrequency device group and 8 patients in the Habib-4X group with complications, respectively, showing no significant difference in overall complications between the two groups ( χ2=1.292, P>0.05). The number of deaths in the new internal cooling circulation bipolar radio frequency device group and Habib-4X group was 0 and 1, respectively, showing no significant difference between the two groups ( P>0.05). Conclusion:The new internal cold-circulating bipolar radio frequency device for open hepatectomy is safe and effective, which cuts the liver parenchyma faster, has lower carbonization rate at the tip of electrode needle, and has more accurate coagulation range.
9.Curative effect analysis of ultrasound-guided percutaneous radiofrequency ablation for caudate lobe hepatocellular carcinoma
Yanzhao ZHOU ; Ruili ZHU ; Zhengzheng WANG ; Keli YU ; Qingjun LI ; Jinxue ZHOU
Chinese Journal of Hepatology 2021;29(7):690-695
Objective:To investigate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) for caudate lobe hepatocellular carcinoma (HCC) and the failure factors of incomplete tumor ablation.Methods:Twenty-four cases with caudate lobe hepatocellular carcinoma who underwent ultrasound-guided percutaneous RFA in the Affiliated Tumor Hospital of Zhengzhou University from January 2017 to October 2019 were enrolled. The ablation effect and complications conditions were recorded, and the primary technical effectiveness and local tumor progression (LTP) were evaluated.Results:Among 24 cases, 20 cases had complete ablation at one session, 4 cases had incomplete ablation, and after supplementary radiofrequency ablation all cases had achieved complete ablation. There was no evidence of local tumor progression in 24 cases after one-month postoperative evaluation. The primary technical effectiveness rate was 100%. The postoperative follow-up was 2 to 29 months (median follow-up time was 18 months). Of the 24 cases after ablation, LTP were detected in 11 cases, of which only 3 cases had distant intrahepatic recurrence, 1 case had distant intrahepatic recurrence and distant metastasis, and 5 cases had only distant metastasis, 2 cases died, and 4 cases had SIR grade B complications related to ablation.Conclusion:Ultrasound-guided percutaneous radiofrequency ablation was safe and effective for caudate lobe hepatocellular carcinoma. In addition, the distance between the tumor and the inferior vena cava < 0.5cm is a suspected risk factor for incomplete ablation of caudate lobe hepatocellular carcinoma ( P < 0.05).
10.Effect of 1 470nm laser anterograde enucleation on BPH and its influence on stress response and quality of life
Chinese Journal of Primary Medicine and Pharmacy 2020;27(14):1720-1724
Objective:To observe the effect of 1 470nm laser anterograde enucleation on benign prostatic hypertrophy (BPH), and its influence on stress response and quality of life.Methods:From July 2018 to May 2019, 90 patients with BPH diagnosed and treated by urology department in Rizhao Central Hospital were selected in the study.According to the different treatment methods, they were divided into two groups, with 45 cases in each group.In the observation group, 1 470nm laser anterograde enucleation of prostate was used.The control group was treated with transurethral plasma resection.The operation time, bladder flushing time, indwelling catheter time and hospitalization time of the two groups were compared.The stress responses of the two groups were compared, including CK, CRP, cortisol and adrenaline levels.The differences of IPSS score, QOL score, maximum urine flow rate (Qmax) and residual urine test (PVR) between the two groups were compared after 6 months of follow-up.The incidence of complications of the two groups was compared.Results:The operation time of the observation group was significantly longer than that of the control group[(80.2±23.5)min vs.(69.5±19.2)min], and the bladder washing time[(1.4±0.3)d vs.(1.7±0.4)d], indwelling catheter time[(5.2±0.9)d vs.(6.2±1.1)d] and hospitalization time[(6.7±1.1)d vs.(8.3±1.6)d] were significantly shorter than those of the control group ( t=4.576, 4.025, 4.719, 5.528, all P<0.05). After operation, the levels of CK[(100.5±11.5)U/L vs.(86.5±9.2)U/L, (103.5±15.4)U/L vs.(87.3±9.9)U/L], CRP[(14.5±2.9)mg/L vs.(12.5±2.5)mg/L, (16.3±3.1)mg/L vs.(12.6±1.9)mg/L], cortisol[(285.2±45.6)ng/mL vs.(235.6±36.5)ng/mL, (310.2±55.6)ng/L vs.(241.6±43.2)ng/L] and adrenaline[(57.8±8.7)pg/mL vs.(51.5±7.8)pg/mL, (62.5±9.9)pg/L vs.(50.9±8.9)pg/L] in the two groups were significantly higher than those before operation ( t=6.377, 6.478, 3.504, 5.125, 5.696, 6.752, 3.617, 4.992, all P<0.05). The levels of CRP, cortisol and adrenaline in the observation group were significantly lower than those in the control group (all P<0.05). After operation, the IPSS score[(7.5±1.6)points vs.(24.2±6.8)points, (7.7±1.9)points vs.(23.8±7.6)points] and QOL score[(1.4±0.5)points vs.(5.0±0.6)points, (1.6±0.6)points vs.(4.9±0.7)points] of the two groups were significantly reduced, Qmax[(21.7±3.5)mL/s vs.(7.5±2.1)mL/s, (22.1±4.3)mL/s vs.(7.8±2.5)mL/s] were significantly increased, PVR[(28.6±7.2)mL vs.(111.2±26.5)mL, (29.3±8.1)mL vs.(114.5±32.5)mL] were significantly increased, the differences were statistically significant ( t=16.037, 14.251, 30.920, 27.528, 23.338, 22.527, 20.178, 21.852, all P<0.05), but there were no statistically significant differences between the two groups (all P>0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:1 470nm laser anterograde enucleation of prostate is a reliable method for the treatment of BPH.

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