Development of highly potent non-covalent inhibitors of SARS-CoV-2 3CLpro

The SARS-CoV-2 virus is the causal agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19). There is an urgent need for potent, specific antiviral compounds against SARS-CoV-2. The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses, and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, non-covalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. One-Sentence SummaryA oral non-covalent inhibitor of 3C-like protease effectively inhibits SARS-CoV-2 replication.

Susceptibilities of human ACE2 genetic variants in coronavirus infection

The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in more than 1603 million cases worldwide and 3.4 million deaths (as of May 2021), with varying incidences and death rates among regions/ethnicities. Human genetic variation can affect disease progression and outcome, but little is known about genetic risk factors for SARS-CoV-2 infection. The coronaviruses SARS-CoV, SARS-CoV-2 and HCoV-NL63 all utilize the human protein angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells. We hypothesized that the genetic variability in ACE2 may contribute to the variable clinical outcomes of COVID-19. To test this hypothesis, we first conducted an in silico investigation of single-nucleotide polymorphisms (SNPs) in the coding region of ACE2 gene. We then applied an integrated approach of genetics, biochemistry and virology to explore the capacity of select ACE2 variants to bind coronavirus spike protein and mediate viral entry. We identified the ACE2 D355N variant that restricts the spike protein-ACE2 interaction and consequently limits infection both in vitro and in vivo. In conclusion, ACE2 polymorphisms could modulate susceptibility to SARS-CoV-2, which may lead to variable disease severity.

Transrectal ultrasound/multiparametric magnetic resonance imaging fusion targeted biopsy for the clinically significant prostate cancer detection / 中华超声影像学杂志

Objective:To explore the diagnostic value of transrectal ultrasound(TRUS)/multiparametric magnetic resonance imaging(mpMRI) fusion targeted biopsy(FTB) for clinically significant prostate cancer(PCa) detection by using both biopsy histopathology and radical prostatectomy histopathology as reference standards.Methods:A total of 303 consecutive patients with suspicious lesions detected by mpMBI and underwent prostate biopsy at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between November 2017 to January 2020 were retrospectively analyzed. All the suspicious lesions were sampled by TRUS/mpMRI FTB in addition with standard 12-core systematic biopsy(SB). The clinically significant PCa detection rates by TRUS/mpMRI FTB and SB were compared by using both biopsy histopathology and radical prostatectomy histopathology as reference standards.Results:The diagnosis of PCa was histologically confirmed in 189 of 303 patients, including 178 patients with clinically significant PCa and 11 patients with clinically insignificant PCa. With biopsy histopathology as reference standard, the clinically significant PCa detection rate of TRUS/mpMRI FTB was statistically higher than SB (57.1% vs 45.9%, P<0.001). Among 189 patients with biopsy proven PCa, 80 patients underwent radical prostatectomy, and the radical prostatectomy histopathology confirmed 79 patients with clinically significant PCa.With radical prostatectomy as reference standard, the clinically significant PCa detection rate of TRUS/mpMRI FTB was statistically higher than SB (91.1% vs 74.7%, P<0.001). Conclusions:Compared with SB, MRI/US FTB can offer more accurate sampling of suspicious lesions on mpMRI, and consequently improve the clinically significant PCa detection rate.

A novel cell culture system modeling the SARS-CoV-2 life cycle

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the global pandemic of COVID-19, and no effective antiviral agents and vaccines are available. SARS-CoV-2 is classified as a biosafety level-3 (BLS-3) agent, impeding the basic research into its biology and the development of effective antivirals. Here, we developed a biosafety level-2 (BSL-2) cell culture system for production of transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). This trVLP expresses a reporter gene (GFP) replacing viral nucleocapsid gene (N), which is required for viral genome packaging and virion assembly (SARS-CoV-2-GFP/{Delta}N trVLP). The complete viral life cycle can be achieved and exclusively confined in the cells ectopically expressing SARS-CoV or SARS-CoV-2 N proteins, but not MERS-CoV N. Genetic recombination of N supplied in trans into viral genome was not detected, as evidenced by sequence analysis after one-month serial passages in the N-expressing cells. Moreover, intein-mediated protein trans-splicing approach was utilized to split the viral N gene into two independent vectors, and the ligated viral N protein could function in trans to recapitulate entire viral life cycle, further securing the biosafety of this cell culture model. Based on this BSL-2 SARS-CoV-2 cell culture model, we developed a 96-well format high throughput screening for antivirals discovery. We identified salinomycin, tubeimoside I, monensin sodium, lycorine chloride and nigericin sodium as potent antivirals against SARS-CoV-2 infection. Collectively, we developed a convenient and efficient SARS-CoV-2 reverse genetics tool to dissect the virus life cycle under a BSL-2 condition. This powerful tool should accelerate our understanding of SARS-CoV-2 biology and its antiviral development.

ORF3a mediated-incomplete autophagy facilitates SARS-CoV-2 replication

SARS-CoV-2 is the causative agent for the COVID-19 pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin-1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 28 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate Beclin-1-Vps34-Atg14 complex but selectively inhibit Beclin-1-Vps34-UVRAG complex. Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raises the possibility of targeting the autophagic pathway for the treatment of COVID-19.

Comparative analysis reveals the species-specific genetic determinants of ACE2 required for SARS-CoV-2 entry

Coronavirus interaction with its viral receptor is a primary genetic determinant of host range and tissue tropism. SARS-CoV-2 utilizes ACE2 as the receptor to enter host cell in a species-specific manner. We and others have previously shown that ACE2 orthologs from New World monkey, koala and mouse cannot interact with SARS-CoV-2 to mediate viral entry, and this defect can be restored by humanization of the restrictive residues in New World monkey ACE2. To better understand the genetic determinants behind the ability of ACE2 orthologs to support viral entry, we compared koala and mouse ACE2 sequences with that of human and identified the key residues in koala and mouse ACE2 that restrict viral receptor activity. Humanization of these critical residues rendered both koala and mouse ACE2 capable of binding the spike protein and facilitating viral entry. The single mutation that allowed for mouse ACE2 to serve as a viral receptor provides a potential avenue for the development of SARS-CoV-2 mouse model.

The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission

The global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission.

Contrast-enhanced ultrasound targeted biopsy for the clinically significant prostate cancer detection / 中华超声影像学杂志

Objective:To assess the utility of contrast-enhanced ultrasound (CEUS) targeted biopsy (TB) for clinically significant prostate cancer (PCa) detection.Methods:A total of 983 consecutive patients scheduled for prostate biopsy from October 2015 to March 2019 in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were enrolled in this retrospective study. All patients had suspicious lesions on CEUS, defined as increased focal contrast enhancement, rapid contrast enhancement and low enhancement lesions with ill-defined borders. Suspicious lesions on CEUS were sampled in addition with standard 12-core systematic biopsy(SB). Clinically significant PCa was defined using Epstein criteria. The clinically significant PCa detection rate by CEUS-TB and combined biopsy was evaluated in comparison with SB.Results:In 502 of the 983 patients, the diagnosis of PCa was histologically confirmed, including 445 patients with clinically significant PCa and 57 patients with clinically insignificant PCa. The clinically significant PCa by CEUS-TB and combined biopsy were 41.9% (412/983) and 45.3% (445/983) respectively, which was significantly higher than SB (36.8%, 362/983)(all P<0.001). CEUS-TB resulted in additional 83 cases of clinically significant PCa, including 61 patients missed by SB and 22 patients under-graded by SB. Conclusions:CEUS is helpful in the detection of PCa lesions. Combined CEUS-TB and SB can improve the clinically significant PCa detection rate.

Comparison of contrast-enhanced ultrasound targeted biopsy versus standard systematic biopsy for clinically significant prostate cancer detection: results of a prospective cohort study with 1024 patients.

PURPOSE: To assess contrast-enhanced ultrasound (CEUS) targeted biopsy (TB) for clinically significant prostate cancer (PCa) detection compared with systematic biopsy (SB). METHODS: A total of 1024 consecutive patients scheduled for prostate biopsy were enrolled in this prospective study. CEUS was performed by an experienced radiologist blinded to all clinical data. Suspicious lesions on postcontrast images were sampled in addition to standard 12-core SB. The clinically significant PCa detection rate by CEUS-TB was evaluated in comparison with SB in the total cohort and in different subgroups. RESULTS: In 378 of 1024 patients (36.9%), the diagnosis of PCa was histologically confirmed. PCa was detected by CEUS-TB in 306 patients (29.9%, 306/1024) and SB in 317 patients (31.0%, 317/1024, P = 0.340). Among 378 PCa patients, 326 (86.2%, 326/378) were diagnosed with significant PCa using Epstein criteria. The significant PCa detection rate of CEUS-TB was 28.7% (294/1024), which was higher than that of SB (25.3%, 259/1024, P = 0.000). CEUS-TB resulted in 67 additional cases of clinically significant PCa, including 51 patients missed by SB and 16 patients under-graded by SB. Conversely, SB detected 32 additional significant PCa missed by TB. In the subgroup analysis, CEUS-TB yielded a higher significant cancer detection rate than SB in patients with a PSA level ≤ 10.0 ng/ml or prostate volume from 30 to 60 ml. CONCLUSION: The clinically significant PCa detection rate could be improved by the extra sampling of abnormalities on postcontrast images, especially in patients with a PSA level ≤ 10.0 ng/ml or prostate volume from 30 to 60 ml.

The value of contrast enhanced ultrasound in breast cancer biopsy / 中华超声影像学杂志

Objective@#To retrospectively investigate the value of contrast enhanced ultrasound (CEUS) in breast cancer biopsy.@*Methods@#A total of 49 consecutive patients with biopsy confirmed breast cancer were retrospectively analyzed. All patients underwent CEUS and biopsies were thus performed targeting both the high perfusion and low/non-perfusion regions on CEUS. The diagnostic performance and core cancer involvement of the biopsy cores taken from the high perfusion regions were compared with those from the low/non-perfusion.@*Results@#A total of 53 breast cancer lesions were biopsy confirmed in 49 patients.CEUS revealed homogeneous enhancement in 8 lesions (15.1%), and heterogeneous enhancement in 45 lesions (84.9%). The diagnostic accuracy rate for biopsy cores taken from the high perfusion regions was significantly higher than that from the low/non-perfusion regions (98.5% vs 72.9%, P<0.01). The core cancer involvement was also higher in high perfusion lesions (55% vs 30%, P<0.01).@*Conclusions@#CEUS can differentiate the active area and necrotic fibrosis area of breast tumors by displaying the microvessels, thus contributing to the selection of biopsy sites.

The value of contrast enhanced ultrasound in breast cancer biopsy / 中华超声影像学杂志

Objective To retrospectively investigate the value of contrast enhanced ultrasound ( CEUS) in breast cancer biopsy . Methods A total of 49 consecutive patients with biopsy confirmed breast cancer were retrospectively analyzed . All patients underwent CEUS and biopsies were thus performed targeting both the high perfusion and low/non‐perfusion regions on CEUS . T he diagnostic performance and core cancer involvement of the biopsy cores taken from the high perfusion regions were compared with those from the low/non‐perfusion . Results A total of 53 breast cancer lesions were biopsy confirmed in 49 patients .CEUS revealed homogeneous enhancement in 8 lesions ( 15 .1% ) ,and heterogeneous enhancement in 45 lesions ( 84 .9% ) . T he diagnostic accuracy rate for biopsy cores taken from the high perfusion regions was significantly higher than that from the low/non‐perfusion regions ( 98 .5% vs 72 .9% , P ＜0 .01) . T he core cancer involvement was also higher in high perfusion lesions ( 55% vs 30% , P ＜0 .01) . Conclusions CEUS can differentiate the active area and necrotic fibrosis area of breast tumors by displaying the microvessels ,thus contributing to the selection of biopsy sites .

The value of color Doppler ultrasonography in the differential diagnosis of benign and malignant testicular tumors in children / 中华超声影像学杂志

Objective To investigate the value of color Doppler ultrasonography in the differential diagnosis of benign and malignant testicular tumors in children. Methods The sonographic findings of 63 children pathologically confirmed testicular tumors were retrospectively analyzed.All children were divided into benign group and malignant group according to pathologic diagnosis. The tumor size,shape,border, echo texture,calcification and color blood flow were compared between two groups. Logistic regression analysis was employed to predict sonographic features of benign and malignant testicular tumors.Receiver operating curve (ROC) was employed to assess the diagnostic performance of sonographic features. Results Among the 63 cases of pediatric testicular tumors,42 cases were histologically confirmed as benign testicular tumors (66.7% ),and the rest 21 cases were malignant testicular tumors (33.3% ). The maximum diameter of tumor in benign tumors was significantly smaller than that in malignant tumors[(1.75 ± 0.75) cm vs (2.90 ± 1.22)cm,P =0.000].In the sonographic features,malignant testicular tumors were more likely to present with solid masses,and benign testicular tumors were more likely to be cystic or cystic-solid ( P =0.024).Calcification was more common in benign tumors than that in malignant tumors ( P =0.000).Compared with benign tumors,malignant tumors had increased blood flow on color Doppler images ( P =0.000).Logistic regression analysis indicated that flow grade was the independent prognostic factors for malignant tumor. By using Alder grade of 2 or above as threshold,the sensitivity,specificity and accuracy were 95.2%,78.6% and 84.1%,respectively. Conclusions The sonographic features vary between benign and malignant testicular tumors. Blood flow is the independent factors for predicting malignant tumor. Color Doppler ultrasonography is an important method for differential diagnosis of testicular tumors in children.

The influence of prostate volume on prostate cancer detection using real-time elastography targeted biopsy / 中华超声影像学杂志

Objective To retrospectively evaluate the influence of prostate volume on prostate cancer detection using elastography targeted transperineal biopsy. Methods A total of 573 consecutive patients suspicious for prostate cancer were enrolled in this study. Patients underwent combined elastography-targeted biopsy and 10 core-systematic transperineal biopsy.In correlation with prostate biopsy pathology, the sensitivity of elastography-targeted biopsy and systematic biopsy were compared among four subgroups with different prostate volume.Results The overall prostate cancer detection rate was 42.9% (246/573). The increase in cancer detection rate by elastography-targeted biopsies was 9.1% (52/573).In patients with prostate volume of ≤30 ml,30-50 ml,50 -80 ml and >80 ml,the sensitivity of elastography targeted biopsy were 91.1% (72/79),81.3% (87/107),70.5% (31/44) and 50.0% (8/16),respectively ( P =0.000).The sensitivity of systematic biopsy were 77.2% (61/79),77.6% (83/107),86.4% (38/44) and 75.0% (12/16),respectively,in comparison among these four groups ( P = 0.601). For patients with prostate volume ≤30 ml,the sensitivity of elastography targeted biopsy was significantly higher than that of systematic biopsy (P= 0.028). Conclusions Prostate cancer detection rate can be improved by elastography targeted biopsy. Prostate volume is correlated with the accuracy of elastography. The sensitivity of elastography targeted biopsy is higher in patients with a smaller prostate gland.

Predictive value of postoperative ultrasonographic parameters regarding the outcome after TURP for patients with symptomatic BPH / 中华泌尿外科杂志

Objective To evaluate the value of preoperative ultrasonographic parameters in predicting the outcome of TURP.Methods A total of 202 patients with symptomatic benign prostatic hyperplasia (sBPH) entering our department for surgical therapy were prospectively recruited,with mean age of (65.5 ± 8.1) years,international prostate symptom score (IPSS) of 16.6 ± 8.1 and quality of life (QOL) score of 5 (3,6).Preoperative combined test of ultrasonography and urodynamics has found total prostate volume (TPV),transitional zone volume (TZV),transitional zone index (TZI),intravesical prostatic protrusion (IPP),resistive index (RI),postvoiding residue (PVR),detrusor wall index (DWT),ultrasonic estimation of bladder weight (UEBW) and maximum flow rate (Qmax) to be (75.0 ±38.5) ml,(49.9 ± 32.4) ml,0.59 ±0.14,(17.2 ±5.0) mm,0.63 ±0.12,(132.7 ±97.8)ml,(16.3 ±7.9)mm,(44.8 ± 7.1)g and (6.1 ± 6.0)ml/s respectively.A 6-monthsfollow-up after standard TURP were applied including re-measurement of IPSS,QOL score and Qmax.The patients were classified into 2 groups of effective and ineffective after the recovery being stratified into 4 levels of none,fair,good and excellent.The influence of preoperative ultrasonographic parameters on surgical outcome was analyzed by logistic regression and receiver operating characteristic (ROC) curve.Results The group of effective has 149 patients,with the preoperative TZI,IPP,RI,DWT and UEBW of 0.65 ± 0.27,(18.3 ± 3.1) mm,0.77 ± 0.18,(19.0 ± 5.0) mm and (46.6 ± 7.1) g,which were significantly higher than that of the group of ineffective (P ＜ 0.05) Lower RI,DWT and UEBW were found to be risk factors of unfavorable surgical efficacy (P ＜ 0.05) from multivariable analysis.The area under curve (AUC) of RI,DWT and UEBW in outcome prediction was 0.816,0.732 and 0.723 respectively from ROC curve,indicating the good predictive value of the 3 parameters with combined positive predictive value (PPV) of 96.3％.Conclusion RI,DWT and UEBW have favorable value in predicting TURP outcome.Measuring these parameters by preoperative ultrasonography might aid in determining the need for surgical intervention in sBPH patients.

Transrectal contrast enhanced ultrasound targeted biopsy for detection prostate cancer:comparison with systematic biopsy / 中华超声影像学杂志

Objective To assess transrectal contrast enhanced ultrasound (CEUS ) targeted biopsy (TB) for detection prostate cancer (PCa) by comparing with systematic biopsy (SB) .Methods 151 consecutive patients scheduled for prostate biopsy were enrolled in this prospective study with a mean age of 68 8.± 8 0. (47-86) and prostate specific antigen (11 5.± 6 9.)μg/L (0 3.-39 8.μg/L) .CEUS was performed by a single experienced radiologist who was blinded to all clinical data with the Sequoia 512 ultrasonography system equipped with EV8C4 endfire probe .Hypoperfusion lesions ,hyperperfusion lesions and lesions with rapid wash‐in or wash‐out were suspicious for malignant ,and these lesions were sampled with 2-4 cores in addition with 10‐core SB .Results The overall PCa detection rate was 40 4.% (61/151) .Of 61 PCa patients , 11 (18 0.% ) had positive cores in TB ,18 (23 0.% ) had positive cores in SB and 36 (59 0.% ) had positive cores in both biopsy protocols .The PCa detection rate of TB and SB was 33 1.% and 31 1.% respectively (P=0 7.12) .A total of 1 755 cores were sampled including 1 510 SB cores and 245 TB cores .The positive rate for TB was significantly higher than SB (52 2.% vs 11 5.% ,P =0.000) .Of 61 PCa patients ,18 had low‐grade cancer (Gleason score<7) and 43 had high‐grade cancer (Gleason score≥7) .The sensitivity for high‐grade PCa was 86 0.% with TB ,which was significantly higher than low‐grade cancer (55 6.% ,P =0.018) . Conclusions The PCa detection rate of CEUS‐TB was equal with SB ,whereas the positive rate by core of CEUS‐TB was significant higher than SB .Furthermore ,CEUS‐TB was more sensitive in detection of high grade prostate cancer .

Value of real-time elastography guided transperineal prostate biopsies in improving prostate cancer detection rate / 中华超声影像学杂志

Objective To determine the utility of elastography guided biopsies in men undergoing transrectal ultrasound-guided transperineal prostate biopsies.Methods A total of 108 consecutive patients suspicious for prostate cancer due to elevated serum prostate specific antigen level or abnormal digital rectal examination were enrolled in this prospective study.All patients underwent combined elastography-targeted and 10 core-systematic transperineal biopsy.The impact of elastography-targeted biopsies on the prostate cancer detection rate was analyzed in comparison with prostate biopsy pathology.Results The overall prostate cancer detection rate was 49.1％ (53/108).The prostate cancer detection rate of systematic biopsy was 35.2％(38/108).The increase in cancer detection rate by elastography-targeted biopsies was 13.9％(15/108,P =0.039).A total of 1296 cores were sampled among 108 patients,including 1080 systematic biopsy cores and 216 targeted biopsy cores.The positive rate of targeted biopsy was significantly higher than systematic biopsy (50.9％ vs 14.1％,P ＜0.0001).Conclusions Prostate cancer detection rate could be significantly improved by elastography targeted transperineal biopsy.

Value of contrast-enhanced ultrasonography in assessing peripheral zone prostate cancer aggressiveness / 中华超声影像学杂志

Objective To determine whether cadence contrast pulse sequencing (CPS) harmonic ultrasonography can be used to predict aggressiveness of peripheral zone prostate cancer.Methods CPS harmonic ultrasonography was performed in 62 biopsy-proved prostate cancer patients.Time intensity curves were reconstructed for biopsy-proved or radical prostatectomy histopathology proved prostate cancer lesions.The characteristics of the curves were described using hemodynamic parameters including arrival time (AT),time-to peak (TTP) and peak intensity (PI).The differences of hemodynamic parameters between different Gleason score and pathologic stage were analyzed.Results Prostate biopsy revealed 156 peripheral zone prostate cancer lesions among 62 patients,including 40 low grade lesions and 116 high grade lesions.In comparison with low-grade lesions,the contrast agents arrived and distributed earlier in highgrade lesions (P =0.005,0.023).In addition to lower AT and TTP,high-grade tumors had higher PI than low-grade tumors (P =0.008).Among 21 patients underwent radical prostatectomy,histopathology documented 14 low grade tumors and 17 high grade tumors,significant differences of hemodynamic parameters were found between these two groups (P ＜0.05).Furthermore,prostate cancer lesions with extra capsular extension also had high PI than those confined in the gland (P =0.000).Conclusions Contrast-enhanced ultrasound and hemodynamic parameters might be helpful in predicting aggressiveness of prostate cancer.

Efficacy of combination therapy with 5 alpha-reductase inhibitor and alpha-receptor blocker for the treatment of intravesical prostatic profusion in patients with benign prostatic hyperplasia / 中华老年医学杂志

Objective To evaluate the efficacy of combination therapy with finasteride and doxazosin in benign prostatic hyperplasia/ lower urinary tract symptoms (BPH/LUTS) patients with intravesical prostatic profusion (IPP).Methods A total of 322 BPH/LUTS patients who accepted combination therapy with finasteride and doxazosin were enrolled in this study.Patients were divided into 4 groups according to the degree of IPP:group Ⅰ(IPP＞10 mm),group 2 (IPP between 5 mm and 10 mm),group 3 (IPP＜5 mm),control group (without IPP).All patients were received inasteride 5 mg once per day and doxazosin 4 mg once per day for 6 months.International prostate symptom score (IPSS),prostatic specific antigen(PSA),ultrasonographic and urcdynamic evaluation were compared before and after treatment.The correlations between the above factors and IPP were estimated by Logistic regression analysis.Results After 6 month of treament,the changes of IPP degree and the maximal urinary flow rate (Qmax) had no significant differences in group 1,group 2 and group 3 as compared with before treatment (all P＞0.05).The IPSS in group 1 was not significantly different before and after treatment (P＞0.05).There were significant differences in the PSA level,IPSS,total prostate volume (TPV),transition zone volume (TZV),residual urine volume (PVR) in the 4 groups before and after treatment (all P＜0.05).Logistic regression analysis showed that PVR and Qmax had positive and negative correlations with IPP (P＜0.001 and P=0.024),respectively.Conclusions Combination therapy with finasteride and doxazosin can significantly improve the symptoms of LUST and reduce the total prostate volume in patients with BPH/LUTS,but for BPH patients with IPP,the combination therapy can not effectively alleviate the degree of IPP.The increase of residual urine volume and decrease of Qmax may enhance the risk of bladder outlet obstruction in BPH patients with IPP.

Quantitative evaluation of enhancement degree of prostate cancer with different location on contrast-enhanced transrectal ultrasonography / 中华超声影像学杂志

Objective To analyze the enhancement degree of prostate cancer on contrast-enhanced transrectal ultrasonography (CETRUS) in relation to tumor location.Methods 150 patients suspected of prostate cancer were evaluated with CETRUS.The degree of enhancement of the lesions was objectively measured using peak intensity (PI) with time-intensity curve analysis software.The peak intensity of the lesions located in the medial peripheral zone,the lateral peripheral zone and the transition zone was compared and analyzed.Results Prostate cancer was detected in 96 of 150 patients.The mean PI value of the prostate cancer was significantly higher than that of the benign prostate hyperplasia lesions [(9.88 ± 3.76)dB vs (8.74±4.52)dB,P ＜0.01].The PI value of the cancer foci located in the medial peripheral zone,the lateral peripheral zone and the transition zone increased gradually [(6.55 ± 2.90)dB vs (10.57±2.52)dB vs (13.64±2.38)dB,P ＜0.001].The Spearman correlation coefficient between the tumor location and the PI value was 0.718 (P ＜0.001).The partial correlation coefficient was 0.720 when the Gleason score was used as a covariate (P ＜0.001).Conclusions There was significant difference in enhancement degree between prostate cancer lesions with different location.Being aware of this might be valuable for improving the sensitivity and specificity of CEUS in diagnosis of the prostate cancer.

Transitional Zone Index and Intravesical Prostatic Protrusion in Benign Prostatic Hyperplasia Patients: Correlations according to Treatment Received and Other Clinical Data

PURPOSE: The aim of this research was to assess the value of the transitional zone index (TZI) and intravesical prostatic protrusion (IPP) from transrectal ultrasonography in evaluating the severity and progression of disease by analyzing the relationship between the 2 parameters and symptoms, clinical history, and urodynamics in benign prostatic hyperplasia (BPH) patients undergoing different treatment. MATERIALS AND METHODS: A total of 203 patients receiving medication and 162 patients who underwent transurethral resection of the prostate because of BPH were enrolled in this retrospective analysis. The clinical history and subjective and objective examination results of all patients were recorded and compared after being classified by TZI and IPP level. Linear regression was used to find correlations between IPP, TZI, and urodynamics. RESULTS: The 2 parameters were found to differ significantly between patients receiving medication and patients undergoing surgical therapy (p<0.05). PSA, maximum flow rate (Qmax), detrusor pressure at Qmax (PdetQmax), and the bladder outlet obstruction index (BOOI) differed according to various TZI levels (p<0.05). In addition, the voiding symptom score, Qmax, and BOOI of subgroups with various IPP levels were also significantly different (p<0.05). Both TZI and IPP had significant effects on Qmax, BOOI, and PdetQmax (p<0.05) and the incidence of acute urinary retention (p=0.000). CONCLUSIONS: The results demonstrated that both TZI and IPP had favorable value for assessing severity and progression in patients with BPH. Further studies are needed to confirm whether the two parameters have predictive value in the efficacy of BPH treatment and could be considered as factors in the selection of therapy.