Research Progress of the Roles of Ubiquitination/Deubiquitination in Androgen Receptor Abnormalities and Prostate Cancer / 中国医学科学院学报

Ubiquitin is a small molecule protein consisting of 76 amino acids,widely found in eukaryotic cells. The process by which ubiquitin binding to a specific protein is called ubiquitination. Deubiquitination is the reversed process of ubiquitination. Ubiquitination stimulates downstream signal,including complex assembly,protein conformation and activity changes,proteolysis,autophagy,guilt,chromatin remodeling,and DNA repair. More than 80% of eukaryotic protein degradation is mediated by the ubiquitination system,and ubiquitin-dependent proteolysis is an extremely complex process involving many biomolecular processes. By regulating protein homeostasis,ubiquitination can also regulate a variety of biological processes including cell cycle,cell proliferation,and apoptosis,which are closely related to tumorigenesis and progression. Many abnormalities of androgen receptor (AR) including AR gene amplification,mutation,shear mutation,and AR activity enhancement are closely related to prostate cancer progression. In particular,prostate cancer progression is regulated by the ubiquitination/deubiquitination processes. This article summarizes the recent research advances in the roles of ubiquitination/deubiquitination in AR abnormalities and prostate cancer.

Primary development of visual uroflow scale / 北京大学学报(医学版)

OBJECTIVE@#To develop the visual uroflow scale (VUS), analyze the relationship of VUS score and index of free uroflowmetry, assess urination function preliminarily and improve the work efficiency in the clinic.@*METHODS@#Male lower urinary tract symptoms (LUTS) patients, who attended the Department of Urology in Peking University People's Hospital from March 2016 to March 2017, were assessed for their urination function according to the Visual Uroflow Scale without help from clinicians before undertaking a free uroflowmetry test. And afterwards, a free uroflowmetry was undertaken, and variables including maximal flow rate (Qmax), the average flow rate (Qave) and voiding volume (VV) was obtained. During the study, 124 cases were collected and 53 cases met the inclusion and exclusion criteria and were included in the study cohort. The Spearman correlation analysis was used for analyzing the correlation of VUS scores with free uroflowmetry variables and age. The validity of VUS was evaluated.@*RESULTS@#Most of the patients could choose the very figure matched with self-condition by first instinct without any help from the clinician. The data were analyzed by Spearman correlation analysis. In the present study, voiding time was positively correlated with the VUS score (correlation coefficient, 0.62, P < 0.05). In the present cohort, the patients chose the third and fourth figures to take longer time to urinate, implying worse LUTS situation. Flow time and VUS scores were positively correlated (correlation coefficient, 0.61, P < 0.05). The patients with higher VUS scores would spend more time on urinate, no matter how long urinary hesitation was. Both Qmax and Qave were negatively correlated with the VUS score (correlation coefficient －0.54, －0.62, P < 0.05). The study illustrated that the VUS score suggested that the Qmax basically and further reflected the urination function. And its relationship to age revealed the decreased urination function of aging male, which had reached a consensus.@*CONCLUSION@#Development of VUS has helped the clinician assess the urination function preliminarily at the first time. Patients are assessed for a VUS score before getting surgery or receiving the drug for treatment, and can be re-assessed after. The VUS score can provide an objective quantitative basis to evaluate the treatment efficacy. In addition, considering that it is convenient, timesaving and easy to understand, the VUS is available for follow-up.

Urodynamic classification of male patients with symptoms of overactive bladder and the outcome classification / 北京大学学报(医学版)

OBJECTIVE@#To introduce a urodynamic classification of male patients with symptoms of overactive bladder (OAB) and discuss its clinical significance in practice.@*METHODS@#From January 2015 to January 2017, there were 181 male patients from Peking University People's Hospital who were diagnosed clinically with OAB and underwent preoperative urodynamic test. Finally 126 male patients were enrolled in the research. Male OAB patients could be stratified into four groups based on the chief complaints (whether or not presenting urgency) and the results of urodynamic test (whether or not presenting detrusor overactivity and the ability to stop the involuntary contraction). The contents of this follow-up study included the basic information, the preoperative and postoperative scores of the OAB symptom score (OABSS), the preoperative and postoperative scores of the international prostate symptom score (IPSS), and the amount of the concomitant diseases.@*RESULTS@#According to the classification, the amounts of the four types of OAB patients were 32 (25.40%) for type I, 27 (21.43%) for type II, 59 (46.83%) for type III, and 8 (6.35%) for type IV, respectively. The data of their heights showed no statistical significance (P>0.05). The ages, weights and the amount of the concomitant diseases of type IV were obviously higher than those of the other three types (P<0.05). And the ages, weights and the amount of the concomitant diseases of the other three types had shown no statistical significance (P>0.05). The improvement of the OABSS and IPSS scores of the type IV were obviously inferior to the other three types (P<0.05). The improvements of the OABSS and IPSS scores of type III were obviously higher than those of the other three (P<0.05). The discrepancy of the OABSS and IPSS scores of type I and type II had shown no statistical significance (P>0.05).@*CONCLUSION@#Type IV has the worst outcome and type III has the best among the four types of OAB. And this classification system will certainly have a profound significance in guiding and directing our clinical diagnosis and treatments, and evaluating the prognosis of the patients with OAB.

A case of gastric duplication presenting as a retroperitoneal cystic lesion / 北京大学学报(医学版)

Gastric duplication is a rare congenital anomaly accounting to 4% of all gastrointestinal tract duplications. It is usually diagnosed pre-natally or during infancy. Retroperitoneal gastric duplication is very rare in adult patients. It is generally asymptomatic or presents with non-specific symptoms. The sensitivity of classical imaging modalities for retroperitoneal gastric duplication is weak. Retroperitoneal gastric duplication could be misdiagnosed as other retroperitoneal cystic lesions and it could be definitely diagnosed by typical findings of abdominal enhanced computed tomography (CT) and endoscopic ultrasonography (EUS) plus EUS:guided fine needle aspiration biopsy in gastric duplicated cyst. A female adult patient was diagnosed by an exceptional hospital CT as retroperitoneal cystic lesion and was admitted in our hospital in March 2019. The abdominal enhanced CT in our hospital preoperatively indicated a cystic lesion above the left kidney and the maximum cross section was 9.0 cm×5.2 cm. Lymphocysts and others should be identified and the lesion might be from the stomach. The retroperitoneal gastric duplication was not diagnosed before operation. In the operation laparoscopy revealed the cystic lesion in the retroperitoneum. The pancreas, left adrenal gland, and left kidney were compressed by the cystic lesion. The top of the lesion was connected with the small curvature of the stomach, but it was not communicated with the stomach. The retroperitoneal cystic lesion was completely excised and the surrounding organs were not damaged. The retroperitoneal gastric duplication was clearly diagnosed by the findings in the operation and the pathology of the lesion. The patient was discharged a week after surgery without gastrointestinal and pancreatic injuries. Therefore, the differential diagnosis of retroperitoneal cysts should consider the possibility of retroperitoneal gastric duplication. For patients with typical CT findings or unclear boundaries between the tumor and the stomach wall, gastric duplication could be diagnosed by EUS plus EUS:guided fine needle aspiration biopsy in the cyst. Retroperitoneal gastric duplication cyst could be completely excised by laparoscopy through abdominal cavity and the stomach wall could be completely repaired.

Clinical Features and Diagnosis of Encrusted Bladder Cancer / 中国医学科学院学报

Bladder cancer is a urological malignant tumor with high morbidity and mortality. Masses protruding into the bladder cavity is an important feature for clinical diagnosis of bladder cancer. However,patients with encrusted bladder cancer(EBC)do not present with masses protruding into the bladder cavity and thus this malignancy is often misdiagnosed. Four patients were admitted in Peking University People's Hospital from July 2015 to February 2017. All of them were males aged 40 to 77 years(mean:58 years). Patients were mainly manifested as frequent urination,urgency,nocturia,and decreased bladder capacity,with or without difficulty of voiding.Although the bladder walls were markedly thickened,there was no obvious mass on imaging scans. Three patients received urodynamic test,which showed the maximum capacity of the bladder was 41 to 128 ml(mean:91 ml). One patient presented with gross hematuria,two patients presented with microscopic hematuria,and the remaining one patient had no hematuria. No mass was observed by cystoscopy. All of the patients were diagnosed with bladder cancer by repeated biopsy or intraoperative frozen section analysis.

Clinical application of partial cystectomy with augmentation cystoplasty for invasive bladder cancer in elderly patients / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical effect and safety of biological patch applied in elderly patients with invasive bladder cancer who underwent massive partial cystectomy with augmentation cystoplasty.@*METHODS@#The clinical data of 2 patients with invasive bladder cancer from October 2016 to March 2017, who underwent the massive partial cystectomy with augmentation cystoplasty were retrospectively reviewed. Case one was an 87-year-old man, with tumor located on the bladder anterior wall, ranging from 5.5 cm×2.5 cm, and the grade of American Society of Anesthesiologists (ASA) being III. Case two was a 77-year-old female, whose lesion was located on the right anterior wall, ranging from 5.2 cm×4.0 cm, and the grade of ASA being II. Both of the patients received a massive partial cystectomy with augmentation cystoplasty. The operative time, estimated blood loss, perioperative and postoperative data and follow-up data, including cystoscopy and urodynamics were recorded and compared. When the P value was less than 0.05, it was statistically significant.@*RESULTS@#All the operations were successfully performed. The average operative time was (155.0+35.4) min, mean estimated intraoperative blood loss was 20 to 100 mL, and the mean postoperatively hospital stay was eight days. During the 10 to 14 months' follow-up periods, no local recurrence or distant metastasis occurred. Urodynamic data: the maximum urinary flow rate was 16.5 mL/s, and the maximum bladder capacity was 303 mL. The two patients urinated 3-4 times in the day time, 0 to 3 times in the night, 200-300 mL each time, on average. The American Urological Association symptom score was 3 to 5. Partial cystectomy, applied to aged patients with multiple complications and high risk of surgical anesthesia, was able to reduce surgery related complications. For patients with tumor of small size, the normal bladder wall would be enough to recover functional capacity for urine storing after partial cystectomy. For patients with large lesions range and small normal bladder tissues, augmentation cystoplasty would help recover bladder capacity on the condition of negative margin.@*CONCLUSION@#Massive partial cystectomy with augmentation cystoplasty is safe and effective. It could decrease perioperative morbidity and keep the quality-of-life benefits of bladder preservation, which is worthy of further application for some selected invasive bladder cancer in elderly patients.

Cytotoxic effects of γδT cells on bladder cancer cells and expression of MICA/B in bladder cancer / 北京大学学报(医学版)

OBJECTIVE@#To explore the role of γδT cells against bladder cancer and to detect the expression of stress proteins MICA/B recognized by γδT cells in bladder cancer.@*METHODS@#γδT cells from peripheral blood drawn from 6 bladder cancer patients with pamidronate stimulating were expanded. Flow cytometry was used to detect the purity and expansion folds of γδT cells, and the expression of CD107a on γδT cells after PMA/ionomycin stimulated. The cytotoxicity assay was carried out to test the cytotoxicity of γδT cells against human bladder cancer cell lines. The expression of MICA/B on bladder cancer cell lines and in bladder cancer tissues were detected through flow cytometry and immunohistochemistry respectively.@*RESULTS@#γδT cells from peripheral blood drawn from 6 bladder cancer patients were successfully expanded. The purity was 75%-94% and the expansion folds were 109-371 times. After being stimulated by PMA/ionomycin, the proportion of CD107a+ γδT cells increased significantly, reaching 40%-82%. γδT cells from the 6 bladder cancer patients showed obvious cytotoxic effects on 3 human bladder cancer cell lines which was enhanced as the effector: the target ratio increased. MICA/B were detected both in 3 bladder cancer cell lines and in 26 bladder cancer tissues. The staining score of MICA/B in invasive bladder cancer was slightly higher than that in non-invasive bladder cancer, and in advanced bladder cancer was higher than that in low grade bladder cancer, but the statistical analysis showed that the staining score of MICA/B was no significant correlation between the tissue and the tumor stages and grades.@*CONCLUSION@#γδT cells from the peripheral blood of the bladder cancer patients could be successfully expanded in vitro, and showed significant anti-bladder cancer effect. MICA/B were detected both in bladder cancer cell lines and in bladder cancer tissues. The statistical analysis showed that there was no significant correlation between the staining scores of MICA/B in the tissue and the tumor stages and grades.

Research Advances in Chemokine-like Factor Super Family Member 8 / 中国医学科学院学报

Chemokine-like factor super family member (CMTM) is a novel generic family firstly reported by Peking University Center for Human Disease Genomics. CMTM8 is one member of this family and has exhibited tumor-inhibiting activities. It can encode proteins approaching to the transmembrane 4 superfamily. CMTM8 is down-regulated in most carcinoma cell lines and tissues. Over-expression of CMTM8 may inhibit the proliferation,migration,and invasion of carcinoma cells. However,the exact mechanism of its anti-tumor activity remains unclear. CMTM8 may be involved in various signaling pathways governing the occurrence and development of tumors. CMTM8 may be a new target in the gene therapies for tumors,while further studies on CMTM8 and its anti-tumor mechanisms are warranted.