Biotransformation of Abiraterone Into Five Characteristic Metabolites by the Rat Gut Microbiota and Liver Microsomes.

It is well known that the role of gut microbiota in drug metabolism, especially in oral difficult absorbable drugs. Understanding the gut microbiota could enable us to understand drugs in new ways. The purpose of the study was to investigate explore the metabolites of the anti-prostate cancer drug Abiraterone by examining gut microbiota metabolism and hepatic metabolism in vitro. In this study, five metabolites (M1, M2, M3, M4 and M5) of Abiraterone were discovered using LC/MSn-IT-TOF. Four isomeric metabolites M1-M4 were found in liver microsome. M5 was found in the intestinal contents of Sprague-Dawley rats with a molecular weight of 388.31. Among them, M4 was found to be Abiraterone N-Oxide by comparison with the standard sample. After further comparing the metabolic behavior of Abiraterone in rat gut microbiota and liver microsomes, we delineated the possible metabolic pathways of Abiraterone. In conclusion, Abiraterone is metabolized specifically in liver microsomes and gut microbiota. This study can provide a theoretical basis for elucidating the metabolic mechanism of Abiraterone and guide its rational application in clinic.

No significant association between immunosuppression in solid organ transplantation and prostate cancer risk: a meta-analysis of cohort studies.

BACKGROUND: It is known that organ transplant recipients have a significantly higher risk for developing cancers, but the association between immunosuppression in organ transplantation and the risk for prostate cancer (PCa) remains unclear. We aimed to assess the evidence regarding the association of solid organ transplantation with PCa risk. METHODS: A literature search of the PubMed, Embase, and Web of Science databases was performed up to March 2019. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using a fixed-effect or random-effect model. RESULTS: In total, 26 articles including 33 independent population-based cohort studies with 556,812 recipients and 2,438 PCa cases were identified and included in this meta-analysis. PCa risk in the solid organ transplant recipients did not increase compared with the general population (RR=1.04; 95% CI: 0.90-1.18). Independent analysis of different kinds of organ replacements further indicated immune inhibition in the transplantation of kidney, liver, heart, and lung, and was not associated with elevated PCa risk (RR=0.89; 95% CI: 0.83-0.95; RR=0.61, 95% CI: 0.21-1.02; RR=1.70, 95% CI: 0.88-2.52; RR=0.87, 95% CI: 0.57-1.16, respectively). CONCLUSIONS: This study demonstrated that immunosuppression in solid organ transplant recipients was not associated with higher PCa risk.

IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat model.

BACKGROUND: The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection. METHODS: The expression of IP3R, Grp75, VDAC1, and MCU and mitochondrial Ca2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP3R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP3R, Grp75, and MCU agonists and antagonists on mitochondrial Ca2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy. RESULTS: Increased expression of IP3R, Grp75, VDAC1 and MCU, enhanced interaction among the IP3R-Grp75-VDAC1 complex, mitochondrial Ca2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca2+ overload and podocyte apoptosis, whereas specific antagonists against IP3R, Grp75, or MCU prevented mitochondrial Ca2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats. CONCLUSIONS: This study identified a novel pathway in which the IP3R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca2+ overload. Antagonists that inhibit Ca2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs.

Chlorine levels and species in fine and size resolved atmospheric particles by X-ray absorption near-edge structure spectroscopy analysis in Beijing, China.

An understanding of the species of chlorine is crucial in the metropolis-Beijing, which is suffering serious haze pollution with high frequency. Particulate Matters (PMs) with five different sizes were collected in Beijing from July 2009 to March 2016, and characterized non-destructively by X-ray absorption near edge structure spectroscopy. PM<0.2, PM0.2-0.5 and PM>2.5 contributed for the major PMs mass in spring and summer, PM0.5-1.0 and PM1.0-2.5 contributed for the major PMs mass in autumn and winter. The concentrations of the three chlorine species were in the order of inorganic chlorine (Clinorg) > aliphatic chlorine (Clali) > aromatic chlorine (Claro), indicating that Clinorg constituted the primary chlorine fraction and less toxic Clali constituted the primary total organic chlorine (Clali + Claro, abbreviated as Clorg) in the PMs in Beijing. In addition, these three chlorine species exhibited identical seasonal variation in PM2.5: winter > autumn > spring > summer. Wet precipitation is an important factor to result in the lower mass concentrations of these three chlorine species in summer. The temporal variations of both size resolved PM mass concentrations and chlorine species concentrations suggested that the air pollution prevention and control in Beijing has just won initial success.

[One-puncture one-needle TRUS-guided prostate biopsy for prevention of postoperative infections].

OBJECTIVE: To explore the feasibility and effectiveness of "one-puncture one-needle" transrectal ultrasound (TRUS)-guided prostate biopsy in the prevention of postoperative infections. METHODS: We retrospectively analyzed the clinical data about "one-puncture one-needle" (the observation group) and "one-person one-needle" (the control group) TRUS-guided prostate biopsy performed in the Second People's Hospital of Guangdong Province from January 2005 to December 2015, and compared the incidence rates of puncture-related infection between the two strategies. By "one-puncture one-needle", one needle was used for one biopsy puncture, while by "one-person one-needle", one needle was used for all biopsy punctures in one patient and the needle was sterilized with iodophor after each puncture. RESULTS: Totally, 120 patients received 6+1-core or 12+1-core "one-person one-needle" and 466 underwent 12+1-core "one-puncture one-needle" TRUS-guided prostate biopsy. There were no statistically significant differences between the two groups of patients in age, the prostate volume, the serum PSA level, or the detection rate of prostate cancer (P >0.05). Compared with the control group, the observation group showed remarkably lower incidence rates of puncture-related urinary tract infection (7.5% vs 0.9%, P <0.05), fever (5.0% vs 1.1%, P <0.05), bacteriuria (2.5% vs 0.2%, P <0.05), and total infections (16.7% vs 2.6%, P<0.05) postoperatively. Two cases of bacteremia or sepsis were found in each of the groups, with no significant difference between the two. CONCLUSIONS: "One-puncture one-needle" TRUS-guided prostate biopsy can effectively prevent puncture-related infections.

[Influence of photoselective vaporization of the prostate on the sexual function of the patient].

n recent years, photoselective vaporization of the prostate (PVP) has gained a wide clinical application in the treatment of benign prostatic hyperplasia (BPH) for its satisfactory effect, high safety, and low incidence of complications. With the improvement of living conditions, BPH patients are paying more attention to their sexual function, especially erectile function and ejaculatory problems instead of just focusing on the alleviation of lower urinary tract symptoms. Few studies of PVP, however, relate to its association with the sexual function of the patient and there is a certain controversy over the influence of PVP on it in the existing literature. Prevailing views hold that the uprated power in PVP does not affect erectile function or increase the risk of retrograde ejaculation (REj) and that PVP is even better than transurethral resection of the prostate (TURP) in avoiding the risk of REj.

Transurethral front-firing Greenlight bladder autoaugmentation for bladder contracture: technique and clinical outcomes.

OBJECTIVE: To describe a novel transurethral front-firing Greenlight bladder autoaugmentation for the treatment of bladder contracture and report initial clinical outcomes. METHODS: Between April 2014 and August 2015, five patients diagnosed with contracted bladder were all refractory to conservative treatment and received novel transurethral autoaugmentation. CT scan and urodynamics examination were conducted before operation for disease assessment. Mucosal and muscular layers of bladder wall in fundus were incised vertically and horizontally with front-firing Greenlight laser to enlarge bladder capacity in the operation. Imaging examination and periodical urodynamics study were performed to evaluate the clinical outcomes of the procedure in postoperative follow-up. RESULTS: Transurethral front-firing Greenlight bladder autoaugmentation was performed successfully on all the patients. The mean operative time was 59 min (range 52-65 min) with no significant blood loss. Urodynamic parameters of these patients after operation improved significantly compared with those before operation. Average maximum cystometric capacity (Vmax) increased from 91.2 to 333 ml (p < 0.01), average maximum flow rate (Qmax) ascended from 12.6 to 18.62 ml/min (p < 0.01), and average flow rate (Q(ave)) also increased from 5.74 to 13.18 ml/min (p < 0.01). At the last follow-up, all the patients could void spontaneously with good bladder emptying and their symptoms improved significantly. CONCLUSION: Our novel transurethral front-firing Greenlight bladder autoaugmentation is a safe and effective treatment for contracted bladders. Future studies with larger sample size and long-term follow-up are needed to confirm our findings.

[Vertical Distribution of Heavy Metals and Its Response to Organic Carbon in Red Soil Profile].

The vertical distribution patterns, the source and correlation of heavy metals were characterized in the bulk soil and different soil aggregates of arable red soil profile (0-100 cm) in Hunan province. Their response to organic carbons in proflie was explored as well. Principal component analysis (PCA) suggested that elements could be divided into two principal components, the metals of the first group were Zn,Cu,Pb,As,Cd, and the second group metals were Cr, Ni. Priniciple component elements had similar sources. In 0-30 cm, The first group metals decreased with increasing depth, the second group metals increased with increasing depth. The concentrations of typical heavy metals were in the order of Zn >Cr >Cu >Pb >Ni >As >Cd. Cd in each soil layer was severely polluted, Zn was at level of light pollution, while other metals were at clean levels. In terms of different size of soil aggregate, it was found that colloids played an important role in facilitating transport of heavy metals, such as As, Cu, Zn, Cd, Cr, Ni. While Pb was still mainly enriched in clay component (<53 µm). Infrared spectrum analysis showed that the main functional groups of organic carbon were polysaccharide (22.07%-47.13%), aromatic (13.88%-34.37%) and alcohol (21.04%-59.49%). Correlation analysis showed that stable organic carbon such as polysaccharide and aromatic organic carbon could stablize the metals of first group in profiles, which would delay the migration of heavy metals to deeper soil. However, the active alcohol carbon would enhance the migration.

Effects of lanthanum carbonate on vascular calcification in elderly maintenance hemodialysis patients.

The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2 ± 3.2 and 10.5 ± 2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6 ± 5.9 and 24.8 ± 6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.

Determination of pesticide residues in tea by gas chromatography/triple quadrupole mass spectrometry with solid-phase extraction.

An analytical method was developed for determination of multipesticide residues, including organophosphorus, organohalogen, pyrethroid, and organonitrogen, in tea at trace levels by GC coupled with triple quadrupole mass chromatography (QqQ-MS/MS). Scan time was selected in order to optimize QqQ-MS/MS conditions. The key parameters for controlling cleanup performance were optimized, including SPE cartridge type and elution solvent volume. Acetonitrile was the extraction solvent, and a novel multilayer SPE cartridge, Cleanert TPT, was used in the cleanup step. The recoveries of the studied pesticides at 5.0, 10.0, and 25.0 microg/kg were in the range of 77.8 to 103.8% with an RSD of less than 14%. Determination coefficient (R2) values between 0.9951 and 0.9998 were obtained for all target compounds. The LOD was between 0.002 and 1.0 microg/kg, and LOQs were 0.0066-3.3 microg/kg, which satisfied the maximum residue limits for pesticides in tea recommended by the European Union and Japan. The optimized method was applied to the analysis of real tea samples obtained from the local market.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

[Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia].

OBJECTIVE: To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH). METHODS: Using IIEF-5, we conducted a questionnaire investigation among 210 BPH patients before and after treated by PVP (n = 80) and transurethral resection of the prostate (TURP, n = 130). We also reviewed the clinical data and compared the pre- and post-operative penile erectile function between the two groups of patients. RESULTS: Follow-up was completed in 76 cases of PVP and 123 of TURP. The baseline data showed no statistically significant differences between the two groups in age, prostate volume, IPSS, QOL, Qmax, post void urine residual volume and IIEF-5 scores (P>0.05). Compared with the IEFF-5 score at the baseline (21.88 +/- 2.46), those at 3, 6 and 12 months after PVP were 16.72 +/- 3.17, 19.34 +/- 2.46 and 19.29 +/- 2. 18, respectively, significantly decreased at 3 months (P = 0.042), but with no remarkable difference at 6 and 12 months (P >0.05). Nor were there significant differences in the IIEF-5 score between the PVP and TURP groups at any time points (P>0.05). At 6 months after surgery, the incidence rates of erectile dysfunction were 11.7% and 13.7% in the TURP and PVP groups, respectively (P>0.05). CONCLUSION: PVP may reduce erectile function in some cases in the early stage after surgery, but this adverse effect does not last long and is basically similar to that of TURP.

[Endothelial microparticles and erectile dysfunction: an update].

Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury and/or apoptosis. Microparticles of various cellular origins, such as platelets, leukocytes, and endothelial cells, are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Recent studies show that endothelial microparticles, a kind of envelope particles derived from endothelial cells, not only constitute a marker of endothelial dysfunction, but also play a major biological role in the diagnostic and therapeutic approaches to erectile dysfunction.

Enantioseparation of four organophosphonate derivatives on N-(3,5-dinitrobenzoyl)-L-leucine-n-propylamide stationary phase by molecular modeling.

Four groups of organophosphonate derivatives enantiomers were separated on N-(3,5-dinitrobenzoyl)-S-leucine chiral stationary phase. The three-dimensional structures of the complexes between the single enantiotopic chiral compounds and chiral stationary phase have been studied using molecular model and molecular dynamics simulation. Detailed results regarding the conformation, auto-docking, and thermodynamic estimation are presented. The elution order of the enantiomer could be determined from the energy. The predicted chiral discrimination was obtained by computational results.

A spiking neural network based cortex-like mechanism and application to facial expression recognition.

In this paper, we present a quantitative, highly structured cortex-simulated model, which can be simply described as feedforward, hierarchical simulation of ventral stream of visual cortex using biologically plausible, computationally convenient spiking neural network system. The motivation comes directly from recent pioneering works on detailed functional decomposition analysis of the feedforward pathway of the ventral stream of visual cortex and developments on artificial spiking neural networks (SNNs). By combining the logical structure of the cortical hierarchy and computing power of the spiking neuron model, a practical framework has been presented. As a proof of principle, we demonstrate our system on several facial expression recognition tasks. The proposed cortical-like feedforward hierarchy framework has the merit of capability of dealing with complicated pattern recognition problems, suggesting that, by combining the cognitive models with modern neurocomputational approaches, the neurosystematic approach to the study of cortex-like mechanism has the potential to extend our knowledge of brain mechanisms underlying the cognitive analysis and to advance theoretical models of how we recognize face or, more specifically, perceive other people's facial expression in a rich, dynamic, and complex environment, providing a new starting point for improved models of visual cortex-like mechanism.

[Paratesticular embryonal rhabdomyosarcoma: report of 5 cases and review of the literature].

OBJECTIVE: To improve the diagnosis and treatment of paratesticular embryonal rhabdomyosarcoma (PER). METHODS: We retrospectively studied the clinical data of 5 cases of PER treated from 1997 to 2009 and reviewed the relevant literature, focusing on its clinical manifestations, diagnosis and treatment. RESULTS: The 5 cases of PER, 2 involving the spermatic cord, 2 the testis and 1 the tunica vaginalis, were all treated by radical orchiectomy. Pathologically, 2 cases were classified as stage I, 1 as stage II and 2 as stage IV. Postoperatively, 2 of the patients received chemotherapy and the other 3 refused adjunctive therapy. The patients were followed up for 6, 12, 18 and 28 months, respectively. Four of them remained free from relapse and metastasis, and 1 stage IV patient died of multiple metastasis at 6 months. CONCLUSION: Early diagnosis, radical orchiectomy and adjunctive chemo- or radio-therapy are effective means to the treatment of PER.

Combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells increases benefits in infarcted swine hearts.

OBJECTIVE: Widespread death of implanted cells hampers stem cell therapy for acute myocardial infarction (AMI). Based on the pleiotropic beneficial effects of statins, we examined whether simvastatin (SIMV) increased the efficacy of mesenchymal stem cell (MSC) transplantation after AMI. METHODS AND RESULTS: Chinese miniswine (n=28) were randomized to 1 of 4 groups (n=7 per group): control, SIMV (0.25 mg/kg x d), MSC transplantation, and SIMV+MSCs. AMI was created by ligating the left anterior descending coronary artery; MSCs were injected immediately into the cyanotic myocardium. At 6 weeks, MRI showed the number of dyskinetic segments and the infarct size were significantly decreased in the SIMV group. Cardiac function improved and the perfusion defect decreased significantly in the SIMV+MSC group but not in the MSC-only group (P<0.05, versus control group). MSC survival and differentiation were significantly better in the combination group than in the MSC-only group (P<0.01). Cell apoptosis decreased significantly in both the SIMV and the SIMV+MSC groups but not in the MSC-only group when compared with controls (P<0.05). Furthermore, oxidative stress and inflammatory response was significantly reduced in the infarcted regions in both the SIMV and the SIMV+MSCs groups. CONCLUSIONS: SIMV treatment improves the therapeutic efficacy of MSC transplantation in acutely infarcted hearts by promoting cell survival and cardiovascular differentiation.

Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts.

AIMS: To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium. METHODS AND RESULTS: Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium. CONCLUSION: Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.