The Impact of Prostate Volume on Prostate Cancer Detection: Comparing Magnetic Resonance Imaging with Transrectal Ultrasound in Biopsy-naïve Men.

Background and objective: This study aimed to determine the difference in prostate volume (PV) derived from transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI), and to further investigate the role of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD in prostate cancer (PCa) detection in biopsy-naïve men. Methods: Patients who underwent an initial prostate biopsy within 3 mo after mpMRI between January 2016 and December 2021 were analyzed retrospectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both TRUS-PSAD and mpMRI-PSAD for PCa detection were calculated and compared. The Pearson correlation coefficient, Bland-Altman plot, and receiver operating characteristic curve were also utilized to explore the interests of this study. Key findings and limitations: The median prostate-specific antigen level of 875 patients was 9.79 (interquartile range [IQR]: 7.09-13.50) ng/ml. The median mpMRI-PV and TRUS-PV were 41.92 (IQR: 29.29-60.73) and 41.04 (IQR: 29.24-57.27) ml, respectively, demonstrating a strong linear correlation (r = 0.831, 95% confidence interval: 0.809, 0.850; p < 0.01) and sufficient agreement. No significant difference was observed in terms of the sensitivity, specificity, PPV, and NPV between TRUS-PSAD and mpMRI-PSAD for any PCa and clinically significant PCa (csPCa) detection. The overall discriminative ability of TRUS-PSAD for detecting PCa or non-PCa, as well as csPCa and non-csPCa, was comparable with that of mpMRI-PSAD, and similar results were also observed in the subsequent analysis stratified by mpMRI-PV quartiles, prostate-specific antigen level, and age. The limitations include the retrospective and single-center nature and a lack of follow-up information. Conclusions and clinical implications: TRUS-PV and MRI-PV exhibited a strong linear correlation and reached sufficient agreement. The efficiency of TRUS-PSAD and mpMRI-PSAD for PCa detection was comparable. TRUS could be used for PV estimation and dynamic monitoring of PSAD, and TRUS-PSAD could effectively guide clinical decision-making and optimize diagnostic strategies. Patient summary: In this work, prostate volume (PV) derived from transrectal ultrasound (TRUS) exhibited a strong linear correlation with the PV derived from multiparametric magnetic resonance imaging (mpMRI). The efficiency of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD for the detection of prostate cancer was comparable. TRUS could be used for PV estimation and TRUS-PSAD could help in clinical decision-making and optimizing diagnostic strategies.

Phase State Regulates Photochemical HONO Production from NaNO3/Dicarboxylic Acid Mixtures.

Field observations of daytime HONO source strengths have not been well explained by laboratory measurements and model predictions up until now. More efforts are urgently needed to fill the knowledge gaps concerning how environmental factors, especially relative humidity (RH), affect particulate nitrate photolysis. In this work, two critical attributes for atmospheric particles, i.e., phase state and bulk-phase acidity, both influenced by ambient RH, were focused to illuminate the key regulators for reactive nitrogen production from typical internally mixed systems, i.e., NaNO3 and dicarboxylic acid (DCA) mixtures. The dissolution of only few oxalic acid (OA) crystals resulted in a remarkable 50-fold increase in HONO production compared to pure nitrate photolysis at 85% RH. Furthermore, the HONO production rates (PHONO) increased by about 1 order of magnitude as RH rose from <5% to 95%, initially exhibiting an almost linear dependence on the amount of surface absorbed water and subsequently showing a substantial increase in PHONO once nitrate deliquescence occurred at approximately 75% RH. NaNO3/malonic acid (MA) and NaNO3/succinic acid (SA) mixtures exhibited similar phase state effects on the photochemical HONO production. These results offer a new perspective on how aerosol physicochemical properties influence particulate nitrate photolysis in the atmosphere.

Degradation behaviors of Nabumetone and its metabolite during UV/monochloramine process: Experimental and theoretical study.

This study investigated degradation behaviors of a nonsteroidal anti-inflammatory drug Nabumetone (NMT) and its major metabolite 6-methoxy-2-naphthylacetic acid (MNA) in the coupling process of ultraviolet and monochloramine (UV/NH2Cl). The second-order rate constants of the contaminants reacting with reactive radicals (HO•, Cl•, Cl2•⁻, and CO3•⁻) were determined by laser flash photolysis experiments. HO• and Cl• contributed predominantly with 52.3% and 21.7% for NMT degradation and 60.8% and 22.3% for MNA degradation. The presence of chlorides retarded the degradation of NMT, while promoted the destruction of MNA, which was ascribed to the photosensitization effects of MNA under UV irradiation. Density functional theory (DFT) calculations revealed that radical adduct formation (RAF) was dominant pathway for both HO• and Cl• reacting with the contaminants, and hydrogen atom transfer (HAT) preferred to occur on side chains of NMT and MNA. NMT reacted with NO2• through single electron transfer (SET) with the second-order rate constant calculated to be 5.35 × 107 (mol/L)-1 sec-1, and the contribution of NO2• was predicted to be 13.0% of the total rate constant of NMT in pure water, which indicated that NO2• played a non-negligible role in the degradation of NMT. The acute toxicity and developmental toxicity of NMT were enhanced after UV/NH2Cl treatment, while those of MNA were alleviated. The transformation products of both NMT and MNA exhibited higher mutagenicity than their parent compounds. This study provides a deep understanding of the mechanism of radical degradation of NMT and MNA in the treatment of UV/NH2Cl.

Heavy metals in centralized drinking water sources of the Yangtze River: A comprehensive study from a basin-wide perspective.

Water quality in the Yangtze River Basin (YRB) has received considerable attention because it supplies water to 400 million people. However, the trends, sources, and risks associated with heavy metals (HMs) in water of centralized drinking water sources (CDWSs) in the YRB region are not well understood due to the lack of high-frequency, large-scale monitoring data. Moreover, research on the factors affecting the transportation of HMs in natural water are limited, all of which significantly reduce the effectiveness of CDWSs management. Therefore, this study utilized data on 11 HMs and water quality from 114 CDWSs, covering 71 prefecture-level cities (PLC) in 15 provinces (cities), to map unprecedented geospatial distribution of HMs in the YRB region and examine their concentrations in relation to water chemistry parameters. The findings revealed that the frequency of detection (FOD) of 11 HMs ranged from 28.59% (Hg) to 99.64% (Ba). The mean concentrations are ranked as follows: Ba (40.775 µg/L) > B (21.866 µg/L) > Zn (5.133 µg/L) > V (2.668 µg/L) > Cu (2.049 µg/L) > As (1.989 µg/L) > Mo (1.505 µg/L) > Ni (1.108 µg/L) > Sb (0.613 µg/L) > Pb (0.553 µg/L) > Hg (0.002 µg/L). Concentrations of Zn, As, Hg, Pb, Mo, Sb, Ni, and Ba exhibited decreasing trends from 2018 to 2022. Human activities, including industrial and agricultural production, have led to higher pollution levels in the midstream and downstream of the river than in its upstream. Additionally, the high concentrations of Ba and B are influenced by natural geological factors. Anion concentrations and nutrient levels, play a significant role in the transport of HMs in water. Probabilistic health risk assessment indicates that As, Ba, and Sb pose a potential carcinogenic risk. Additionally, non-carcinogenic risk to children under extreme conditions should also be considered.

Utilization trend of prebiopsy multiparametric magnetic resonance imaging and its impact on prostate cancer detection: Real-world insights from a high-volume center in southwest China.

BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer.

BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Transperineal magnetic resonance imaging targeted biopsy versus transrectal route in the detection of prostate cancer: a systematic review and meta-analysis.

PURPOSE: Magnetic resonance imaging (MRI) has deeply altered the prostate biopsy strategy to detect prostate cancer. However, it is still debatable whether the detection rate differs between transrectal (TR) and transperineal (TP) MRI-targeted biopsy (MRI-TB). To compare the effectiveness of these two methods for detecting both overall prostate cancer (PCa) and clinically significant PCa (csPCa), We performed a review and meta-analysis. METHODS: Until January 2023, we conducted a thorough search of Cochrane, Embase, Ovid, and PubMed. In total, 1482 references were identified, and 15 records were finally included. For PCa and csPCa discovered by TP and TR MRI-TB, we combined the relative sensitivity (RR) with 95% confidence intervals (CI). The RR between the TP and TR routes was established. RESULTS: Our study included 8826 patients in total and revealed that TP MRI-TB detected more PCa (RR 1.25 [95% CI 1.12, 1.39], p < 0.0001). In patients who underwent TP MRI-TB and TR MRI-TB at the same time or separately, TP MRI-TB had a greater detection rate of csPCa in per-patient analysis (one cohort (RR 1.33 [95% CI 1.09, 1.63], p = 0.005); two cohorts (RR 1.37 [95% CI 1.16, 1.61], p = 0.0002)). However, the detection rate of csPCa between the TP route and the TR route was comparable in per-lesion analysis (RR 0.91 [95% CI 0.76, 1.08], p = 0.28). Additionally, in the prostate's anterior region, we found that TP MRI-TB detected more csPCa (per-lesion (RR 1.52 [95% CI 1.04, 2.23], p = 0.03); per-patient (RR 2.55 [95% CI 1.56, 4.16], p = 0.0002)). CONCLUSION: According to this comprehensive study, TP MRI-TB is more effective than TR MRI-TB at detecting PCa and csPCa. Significant results persisted for detecting csPCa located in the anterior zone. The results need to be taken carefully notwithstanding the heterogeneity among the included studies.

Precise Correction of Lhcgr Mutation in Stem Leydig Cells by Prime Editing Rescues Hereditary Primary Hypogonadism in Mice.

Hereditary primary hypogonadism (HPH), caused by gene mutation related to testosterone synthesis in Leydig cells, usually impairs male sexual development and spermatogenesis. Genetically corrected stem Leydig cells (SLCs) transplantation may provide a new approach for treating HPH. Here, a novel nonsense-point-mutation mouse model (LhcgrW495X ) is first generated based on a gene mutation relative to HPH patients. To verify the efficacy and feasibility of SLCs transplantation in treating HPH, wild-type SLCs are transplanted into LhcgrW495X mice, in which SLCs obviously rescue HPH phenotypes. Through comparing several editing strategies, optimized PE2 protein (PEmax) system is identified as an efficient and precise approach to correct the pathogenic point mutation in Lhcgr. Furthermore, delivering intein-split PEmax system via lentivirus successfully corrects the mutation in SLCs from LhcgrW495X mice ex vivo. Gene-corrected SLCs from LhcgrW495X mice exert ability to differentiate into functional Leydig cells in vitro. Notably, the transplantation of gene-corrected SLCs effectively regenerates Leydig cells, recovers testosterone production, restarts sexual development, rescues spermatogenesis, and produces fertile offspring in LhcgrW495X mice. Altogether, these results suggest that PE-based gene editing in SLCs ex vivo is a promising strategy for HPH therapy and is potentially leveraged to address more hereditary diseases in reproductive system.

Diagnosis and treatment of transnasal endoscopic optic canal decompression for traumatic optic neuropathy.

Objective: To investigate the clinical efficacy and prognostic factors of transnasal endoscopic optic decompression in the treatment of traumatic optic neuropathy (TON). Methods: A retrospective analysis was performed on 13 TON patients in The Seventh Affiliated Hospital of Sun Yat-sen University and Shenzhen Eye Hospital in Shenzhen City (China) from June 2020 to April 2022. These patients had received transnasal endoscopic optic decompression, and hormonal and neurotrophic drugs were given after surgery. Visual acuity (VA) improvement was used as the criterion to judge clinical efficacy. Results: In a total of 13 patients, 13 injured eyes (12 men and 1 woman; mean age, 28.0 ± 11.8 years) received transnasal endoscopic optic decompression. After surgery, nine patients had improved VA, whereas four patients failed to show any improvement, resulting in a total effective rate of 69.2%. Of the six patients with no light perception preoperatively, three had effective results after the operation, giving an effective rate of 50.0%. Of the seven patients with residual light sensation preoperatively, six had effective results after the operation, giving an effective rate of 85.7%. Of the 10 patients operated on within 7 days after injury, seven had effective results, giving an effective rate of 70%. Of the three patients injured and operated on after 7 days, two had effective results, giving an effective rate of 66.7%. Conclusion: Transnasal endoscopic optic nerve decompression is an effective treatment method for TON. The presence of residual light perception and the timing of surgery within 7 days are crucial to the prognosis.

Combining clinical parameters and multiparametric magnetic resonance imaging to stratify biopsy-naïve men for an optimum diagnostic strategy with prostate-specific antigen 4 ng ml-1 to 10 ng ml-1.

We attempted to perform risk categories based on the free/total prostate-specific antigen ratio (%fPSA), prostate-specific antigen (PSA) density (PSAD, in ng ml-2), and multiparametric magnetic resonance imaging (mpMRI) step by step, with the goal of determining the best clinical diagnostic strategy to avoid unnecessary tests and prostate biopsy (PBx) in biopsy-naïve men with PSA levels ranging from 4 ng ml-1 to 10 ng ml-1. We included 439 patients who had mpMRI and PBx between August 2018 and July 2021 (West China Hospital, Chengdu, China). To detect clinically significant prostate cancer (csPCa) on PBx, receiver-operating characteristic (ROC) curves and their respective area under the curve were calculated. Based on %fPSA, PSAD, and Prostate Imaging-Reporting and Data System (PI-RADS) scores, the negative predictive value (NPV) and positive predictive value (PPV) were calculated sequentially. The optimal %fPSA threshold was determined to be 0.16, and the optimal PSAD threshold was 0.12 for %fPSA ≥0.16 and 0.23 for %fPSA <0.16, respectively. When PSAD <0.12 was combined with patients with %fPSA ≥0.16, the NPV of csPCa increased from 0.832 (95% confidence interval [CI]: 0.766-0.887) to 0.931 (95% CI: 0.833-0.981); the detection rate of csPCa was similar when further stratified by PI-RADS scores (P = 0.552). Combining %fPSA <0.16 with PSAD ≥0.23 ng ml-2 predicted significantly more csPCa patients than those with PSAD <0.23 ng ml-2 (58.4% vs 26.7%, P < 0.001). Using PI-RADS scores 4 and 5, the PPV was 0.739 (95% CI: 0.634-0.827) when further stratified by mpMRI results. In biopsy-naïve patients with PSA level of 4-10 ng ml-1, stratification of %fPSA and PSAD combined with PI-RADS scores may be useful in the decision-making process prior to undergoing PBx.

"Seminal testosterone", rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study.

Objective: Reproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied. Methods: A bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor's analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time. Results: The b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients' results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest. Conclusion: Seminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463.

AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure.

Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we use a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screen several adeno-associated virus (AAV) serotypes and identify AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observe considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr-/- mice. Of note, this gene therapy partially recovers sexual development, substantially restores spermatogenesis, and effectively produces fertile offspring. Furthermore, these favorable effects can be reproduced in adult Lhcgr-/- mice. Our proof-of-concept experiments in the mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with LCF.

Vessel-Sparing Microsurgical Longitudinal Intussusception Vasoepididymostomy to Treat Epididymal Obstructive Azoospermia.

The epididymis is a common site of obstruction in obstructive azoospermia (OA). Vasoepididymostomy has become an important method for the treatment of epididymal OA since 2000. There are two challenges in classic microscopic vasoepididymostomy. First, anastomosis of the vas deferens and epididymis is performed with double-needle sutures. However, there is a lack of good-quality and cost-effective double-needle sutures in China, which leads to increased difficulty and poor success rates of anastomosis. Second, the separation of the vas deferens does not retain vasculature, although the vas deferens vasculature plays an important role in the blood supply to the vas deferens, epididymis, and testis. This affects the blood supply to the anastomotic area and epididymis. Therefore, this team has made innovative improvements to address these problems. Good-quality, cost-effective, single-needle sutures, which are easy to purchase in China and other countries, were used in microsurgical longitudinal intussusception vasoepididymostomy. This can optimize the operation procedure and shorten the operation time while ensuring the success rate of the anastomosis. The surgical method of preserving the vas deferens vessels was innovatively proposed because the etiology of epididymal OA is mostly inflammatory in China. The protection of the blood supply to the vas deferens and epididymis is maximized using microsurgical forceps to separate and protect the vasculature. Patency reached 81.7% in the postoperative follow-up, indicating a better surgical treatment effect.

The role of prostate-specific antigen density and negative multiparametric magnetic resonance imaging in excluding prostate cancer for biopsy-naïve men: clinical outcomes from a high-volume center in China.

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.

Organic carbon and eukaryotic predation synergistically change resistance and resilience of aquatic microbial communities.

With rapid global urbanization, anthropogenic activities alter aquatic biota in urban rivers through inputs of dissolved organic carbon (DOC) and nutrients. Microorganisms-mediated global element cycles provide functions in maintaining microbial ecology stability. The DOC (bottom-up control) and microbial predation (top-down control) may synergistically drive the competition and evolution of aquatic microbial communities, as well as their resistance and resilience, for which experimental evidences remain scarce. In this study, laboratory sediment-water column experiments were employed to mimic the organic carbon-driven water blackening and odorization process in urban rivers and to elucidate the impact of DOC on microbial ecology stability. Results showed that low (25-75 mg/L) and high DOC (100-150 mg/L) changed the aquatic microbial community assemblies in different patterns: (1) the low DOC enriched K-selection microorganisms (e.g., C39, Tolumonas and CR08G) with low biomass and low resilience, as well as high resistance to perturbations in changing microbial community assemblies; (2) the high DOC was associated with r-selection microorganisms (e.g., PSB-M-3 and Clostridium) with high biomass and improved resilience, together with low resistance detrimental to microbial ecology stability. Overall, this study provided new insight into the impact of DOC on aquatic microbial community stability, which may help guide sustainable urban river management.

[Pollution Characteristics and Risk Assessment of DBPs in Typical Drinking Water Sources in Wuhan Under the COVID-19 Pandemic].

In order to reveal the pollution characteristics and risk levels of DBPs in typical drinking water sources in Wuhan under the COVID-19 pandemic, 26 sampling sites were selected in typical drinking water sources in Wuhan. N,N-diethyl-1,4-phenylenediamine spectrophotometry and gas chromatograph-micro-cell electron capture detector (GC-µECD) methods were used to detect residual chlorine disinfectants and DBPs in water, respectively, and their health and ecology risks were assessed. The results showed that free chlorine or total residual chlorine were detected in 16 of the 26 water samples, and the maximum concentration was 0.04 mg·L-1, which exceeded the limit of the surface water standard in China. The concentration of residual chlorine was higher in sampling sites near the outfall of a municipal sewage plant. There were 34 types of DBPs measured in 10 sampling sites, and 24 types of substances were detected with the detection rate of 10.00%-100.00%. The ρ (total DBPs) was in the range of 0.11-104.73 µg·L-1, with an average value of 7.26 µg·L-1. The concentration of chloroform was the highest among all the DBPs, ranging from 9.98 µg·L-1 to 11.15 µg·L-1, with an average value of 10.47 µg·L-1. The concentration of 2-bromo-2-iodoacetamide was the lowest, ranging from ND-0.11 µg·L-1, with an average value of 0.01 µg·L-1. The overall detection level of the DBPs area was low in this study area, and the result of the health risk assessment showed that the DBPs had no carcinogenic or non-carcinogenic health risks to human body. However, the results of the ecological risk assessment showed that chloroform presented a high ecological risk to aquatic organisms.

[Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows for premature ejaculation: A prospective single-center randomized controlled study].

OBJECTIVE: To investigate the efficacy and safety of Compound Chamomile and Lidocaine Hydrochloride Gel (CCLH) (Kamistad) applied at different time-windows on premature ejaculation (PE). METHODS: This prospective study included 72 PE patients treated by application of CCLH to the glans and penile body in our hospital from February to October 2021. According to the time of drug administration before insertion into the vagina, we randomly divided the patients into a 5-minute group (n = 39) and a 15-minute group (n = 33). Before and after 1 and 2 weeks of treatment, we compared the intravaginal ejaculation latency time (IELT), PE diagnostic tool (PEDT) score, quality of life, and adverse reactions between the two groups of patients. RESULTS: Totally 62 of the patients completed the follow-up, 35 in the 5-minute group and 27 in the 15-minute group, and all showed significant improvement in IELT (P < 0.01) and PEDT score (P < 0.05) after treatment compared with the baseline. No allergic reactions, such as redness and swelling, developed at the application site in any of the patients, and no adverse significant effect was observed on the erectile hardness in 61 of the cases. Six cases showed increased erectile hardness instead. Fifty-seven of the patients experienced no obvious penile numbness or reduced sexual satisfaction, and all could complete their sexual activities. CONCLUSION: Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows is effective on PE, with a 5-minute rapid onset of action before intercourse, and no obvious adverse effects.

Three new andrastin derivatives from the endophytic fungus Penicillium vulpinum.

Three new andrastin derivatives, 10-formyl andrastone A (1), 10-demethylated andrastone A (2) and andrastin G (3), together with four known andrastin analogues (4-7) were isolated from an endophytic fungus Penicillium vulpinum. Their structures were determined by 1 D, 2 D NMR, and the absolute configurations were further determined by experimental and calculated ECD spectra. Compound 5 exhibited significant antibacterial activity against Bacillus paratyphosus B with an MIC value of 6.25 µg·mL-1. Compounds 2 and 6 showed remarkable inhibitory activities against Bacillus megaterium with the MIC value of 6.25 µg·mL-1, respectively.

Efficacy and safety of the new biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy in the detection of prostate cancer: Study protocol for a randomized controlled trial.

Background: Recent EAU guideline strongly recommended combined targeted biopsy (TBx) with systematic biopsy (SBx) for biopsy naïve patients with suspected multiparametric magnetic resonance imaging (mpMRI) lesions; However, the clinical goal is to find out how to determine the optimal SBx and TBx cores for biopsy in order to maximize the detection of csPCa and minimize the associated defects. This study aims to assess the efficacy and safety of the new biopsy strategy combining 6-core systematic and 3-core MRI- TBx compared to 12-core systematic and 3-core MRI-TBx strategy. Methods: This is a single-center, prospectively randomized controlled clinical trial. 280 men meeting inclusion criteria will be recruited and will be randomly allocated to either 6-core systematic plus 3-core MRI-TBx group (Group A) or 12-core systematic plus 3-core MRI-TBx group (Group B). The primary outcome compares the detection rate of PCa and clinically significant prostate cancer(csPCa) between group A and group B. The secondary outcomes compare the participant-reported pain score immediate post biopsy using pain measurement scale; proportion of men with post-biopsy complications and adverse events (Time frame: 7 days post biopsy, 30 days post biopsy); proportion of the men who undergo radical prostatectomy and have cancer upgraded histopathology from the biopsy to the radical prostatectomy. Results and Discussion: A new biopsy strategy should be developed with the goal of minimizing procedure invasion, our study will provide the results of efficacy and safety of the new biopsy strategy (6-core systematic and 3-core MRI-TBx) in biopsy naïve men with suspicious mpMRI lesion in comparison with 12-core systematic and 3-core MRI-TBx. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200056437; http://www.chictr.org.cn/edit.aspx?pid=151413&htm=4.