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The purpose of this study was to investigate the morphological and histological changes in the urethra in beagle dogs after intraurethral Er:YAG laser irradiation in nonablative mode to confirm the safety of this therapy. Six 2-year-old healthy female virgin beagle dogs (13 ± 1.51 kg) were used in this study. The animals were divided into 2 groups: the sham group, which received sham treatment (n = 3) involving insertion of an intraurethral cannula and laser delivery handpiece into the urethra without laser irradiation, and the experimental group (n = 3), which received intraurethral Er:YAG laser irradiation. The laser irradiation parameters were set according to clinical criteria (4 mm spot size, 1.5 J/cm2, 1.4 Hz, and 4 pulses) in nonablative mode. All animals received three sequential sessions at 4-week intervals. Urethrography and urethroscopy were performed in the 12th week and 13th week, respectively, after the first treatment. After urethroscopy, the animals were sacrificed, and urethral tissue was harvested for histological investigations. All procedures were performed under general anesthesia (40 mg/kg 3% sodium pentobarbital, i.v.). Transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression levels were measured to evaluate the biochemical characteristics of the scar. Urethral stricture was not found by urethrography or urethroscopy in either group. Urethral epithelium thickness and collagen expression under the urethral mucosa were significantly increased in the experimental group compared with the sham group. However, there were no significant differences in TGF-β1 and α-SMA expression between the experimental group and sham group (p > 0.05). Urethral stricture is not found in beagle dogs after clinically relevant intraurethral nonablative mode Er:YAG laser irradiation. Proliferation of urethral collagen and the urethral mucosa may be one of the mechanisms by which urine leakage symptoms can be improved.

Erectile dysfunction (ED) is a major health issue among men with diabetes, and ED induced by diabetes mellitus (DMED) is particularly difficult to treat. Therefore, novel therapeutic approaches for the treatment of DMED are urgently needed. Exosomes, nanosized particles involved in many physiological and pathological processes, may become a promising tool for DMED treatment. In this study, we investigated the therapeutic effect of exosomes derived from corpus cavernosum smooth muscle cells (CCSMC‐EXOs) on erectile function in a rat model of diabetes and compared their effect with that of exosomes derived from mesenchymal stem cells (MSC‐EXOs). We incubated labelled CCSMC‐EXOs and MSC‐EXOs with CCSMCs and then observed uptake of the exosomes at different time points using laser confocal microscopy. CCSMC‐EXOs were more easily taken up by CCSMCs. The peak concentration and retention time of labelled CCSMC‐EXOs and MSC‐EXOs in the corpus cavernosum of DMED rats after intracavernous injection were compared by in vivo imaging techniques. Intracavernous injection of CCSMC‐EXOs was associated with a relatively high peak concentration and long retention time. Our data showed that CCSMC‐EXOs could improve erectile function in DMED rats. Meanwhile, CCSMC‐EXOs could exert antifibrotic effects by increasing the smooth muscle content and reducing collagen deposition. CCSMC‐EXOs also increased the expression of eNOS and nNOS, followed by increased levels of NO and cGMP. These findings initially identify the possible role of CCSMC‐EXOs in ameliorating DMED through inhibiting corporal fibrosis and modulating the NO/cGMP signalling pathway, providing a theoretical basis for a breakthrough in the treatment of DMED.

BACKGROUND The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFβ1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

Catalpol, an effective component of China's functional food Rehmannia glutinosa Libosch, has a wide range of pharmacological effects. However, it is unclear whether catalpol exhibits protective and therapeutic potential against rheumatoid arthritis. In this study, the effects of catalpol in rats with collagen II-induced arthritis (CIA) and in LPS-stimulated SW982 human synovial cells were investigated. Catalpol significantly reduced paw swelling and thickness in rats with CIA. Histopathology revealed that catalpol alleviated articular cartilage damage, infiltration of inflammatory cells and synovial hyperplasia. Catalpol also inhibited protein and mRNA levels of IL-6, IL-8 and MMP-1, and the expression of COX-2 and mPGEs-1 in LPS-stimulated SW982 cells. Furthermore, the phosphorylation levels of ERK, JNK, p65, IκBα and c-Jun were suppressed by catalpol. Taken together, these findings showed that catalpol had inhibitory effects against arthritis, which may be related to decreased production of pro-inflammatory mediators and suppression of the MAPK, NF-κB and AP-1 pathways.

Investigating the relationship between landscape pattern and water quality is essential for making sustainable landscape development policies. A clear understanding of such relationship remains elusive partly due to ubiquitous nonlinearity, behind which the landscape threshold can potentially act as quantifiable target of landscape conservation. In the upper Huai River Basin in China, six landscape metrics were quantified for forested, agricultural, and residential land use categories at broad sub-basin and finer riparian buffer scales. Five water quality indicators were collected from 24 monitoring stations during the period of 2006–2012. On the basis of nonlinear regression models, including power, exponential, quadratic, and segmented regressions, one-to-one relations between landscape metrics and water quality variables were fitted with R2 generally varying between 0.32 and 0.74. Meanwhile, three types of defined landscape thresholds were also identified on the basis of the fitted nonlinear relations. From the perspective of spatial scale dependence, the percentage of landscape area and largest patch index could well explain water quality variables at a broad sub-basin scale; the opposite could be said for patch density. The type-1 and type-2 landscape thresholds can act as the long-term targets where landscape pattern management strategy should be timely adjusted. By contrast, the type-3 landscape threshold can be set as a short-term target of landscape conservation to ensure water quality up to a certain management requirement. This study suggests that considering nonlinearity and threshold effect could provide insights into the complicated landscape pattern–water quality relations and thus provide a scientific basis for balancing the coupled socioecological system of landscape development and water quality protection.

BackgroundChoriocarcinoma is a rare malignant tumor and rarely occurs outside the gonads. Primary hepatic choriocarcinoma is more infrequent, with hidden clinical manifestations, rapid progress, and extremely poor prognosis. Only more than 10 cases were publicly reported in the world. Therefore, there is still a lack of deep understanding of the diagnosis and treatment of the disease.Case presentationWe report a case of primary hepatic choriocarcinoma in a man diagnosed by pathology. A 65-year-old male patient presented with fever and anorexia, nothing but mild jaundice of the skin and sclera was found on physical examination. Abdominal enhanced magnetic resonance imaging (MRI) showed a huge mass in the right hepatic lobe. Fludeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) scan showed increased uptake in the liver and sigmoid colon and no uptake in the testes. The patient underwent the right hepatectomy, and postoperative pathology showed that the tumor was primary hepatic choriocarcinoma. Then he received one course of adjuvant chemotherapy. Then he developed severe myelosuppression and was transferred to the intensive care unit for further treatment. He eventually died of severe liver failure about 100 days after surgery. Primary hepatic choriocarcinoma is extremely rare, and its diagnosis is challenging.ConclusionsPrimary hepatic choriocarcinoma is a rare and highly malignant tumor with a poor prognosis. We believe that this differential diagnosis should be considered in liver tumor patients. The effective treatment for this disease is still to be explored.

The phytoplankton community can be affected by multiple environmental factors such as climate, meteorology, hydrology, nutrients, and grazing. The complex interactive effects of these environmental factors as well as the resilience of phytoplankton communities further make the prediction of phytoplankton communities' dynamics challenging. In this study, we analyzed multiple environmental factors and their relative importance in predicting both phytoplankton shifting and cyanobacteria abundance in two regulated shallow lakes in central China. Our results indicated that the phytoplankton community in the study areas could be mainly classified into 1. Cryptophyta dominated group, 2. Biologically diverse group, and 3. Cyanobacteria dominated group. The Multinomial Logistic Regression model indicated the Cryptophyta dominated group was sensitive to temperature, while other groups were sensitive to both temperature and nutrients. The interactive effects of temperature and nutrients were synergistic in the cyanobacteria dominated group, while they were antagonistic or minor in other groups. The Negative Binomial Regression model suggested high total phosphorus and low total nitrogen but not temperature were responsible for high cyanobacteria abundance. The conditional plot indicated nutrients affected cyanobacteria abundance more significantly under low wind speeds and lake volume fluctuations, and cyanobacteria abundance in the cyanobacteria dominated group maintained high levels with increasing hydrological dynamics. Our results demonstrated that environmental factors played inconsistently significant roles in different phytoplankton groups, and reducing nutrients could decrease adverse effects of warming and water project constructions. Our models can also be applied to forecast phytoplankton shifting and cyanobacteria abundance in the management of regulated shallow lakes.

Previous studies have shown that oxidative stress and corporal fibrosis in penile tissues of rats were key pathological factors of erectile dysfunction induced by diabetic mellitus (DMED). Lipoxin A4 (LXA4) was reported to inhibit oxidative stress and fibrosis diseases, while whether it could exert a protective role on erectile function was not clear. Type I diabetic mellitus (DM) was induced in thirty male 10-week-old Sprague-Dawley rats using streptozotocin. Ten weeks later, twenty-two rats with DMED confirmed by an apomorphine test were divided into two groups: the DMED group (n = 11) and the DMED + LXA4 group (n = 11; LXA4 injection daily for 4 weeks). In addition, another ten age-matched rats formed the Control group. We found that erectile function was significantly impaired in the DMED group compared with the Control group, but was improved in the DMED + LXA4 group. Similarly, the over-activated oxidative stress and impaired endothelial function in the DMED group were both improved in the DMED + LXA4 group. Moreover, the DMED group showed serious corporal fibrosis, which was also inhibited by the treatment of LXA4 in the DMED + LXA4 group. Taken together, LXA4 could exert an inhibition role on oxidative stress and fibrosis to improve DMED effectively.

Introduction Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis. Aim To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED). Methods Forty male Sprague-Dawley rats (8 weeks old) were used for the experiment. Thirty-two had type 1 DM induced by streptozotocin and the other eight rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with FTY720 orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks. Main Outcome Measure Metabolic parameters; erectile function; sphingosine-1-phosphate receptor 3 (S1P3), protein kinase B (Akt), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) signaling pathway; corporal fibrosis; apoptosis level; and Smad and non-Smad signaling pathways. Results There were no significant differences in the initial body weights and fasting glucose concentrations among the three groups. Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED + FTY720 group. The DMED group showed inhibited activity of the S1P3-Akt-NO-cGMP signaling pathway, and the inhibition was partly reversed in the DMED + FTY720 group. The DMED group showed serious corporal fibrosis, higher apoptosis level, higher ratio of Bax to Bcl-2, and higher expressions of the Smad pathway (transforming growth factor-β1, Smad, and connective tissue growth factor) and the non-Smad pathway (transforming growth factor-β1, rho-associated protein kinase, LIM domain kinase 2, and cofilin). However, FTY720 supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of Bax to Bcl-2, and inhibited activity of the Smad and non-Smad pathways. Conclusion FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED.

Background The growth and function of seminal vesicle are dependent on androgen. This study was conducted to investigate the role of oxidative stress in castration-induced seminal vesicle atrophy and to explore the effects of curcumin, an antioxidant extracted from rhizome of turmeric, on seminal vesicle of castrated mice. Methods C57BL/6J mice were randomly divided into three groups: control, castration, and castration with curcumin (n = 10 for each group). After surgical castration, mice in the curcumin treatment group received intragastric administration of curcumin at 100 mg/kg body weight for 4 weeks, whereas mice in the other two groups were treated with olive oil. After that, the body weight, seminal vesicle weight and serum testosterone of mice were measured. Apoptosis and oxidative stress levels in seminal vesicle were also determined. Results After castration, both the weight and size of seminal vesicle decreased dramatically. The expression of three NADPH oxidase (NOX) subtypes: NOX1, NOX2 and NOX4, increased in seminal vesicle of castrated mice, resulting in high level oxidative stress. The ratio of Bax to Bcl-2 was also elevated after castration, accompanied by enhanced caspase3 activity. Additionally, castration increased the number of apoptotic cells in seminal vesicle. Curcumin treatment could inhibit the expression of NOX1, NOX2 and NOX4, decreasing oxidative stress and apoptosis. The atrophy of seminal vesicle caused by castration was ameliorated by curcumin. Conclusion Castration could cause atrophy of seminal vesicle probably via inducing oxidative stress. Curcumin treatment could reduce the oxidative stress in seminal vesicle by decreasing the expression of NOX1, NOX2 and NOX4, thereby ameliorating apoptosis and atrophy of seminal vesicle. Oxidative stress might play a role in castration-induced seminal vesicle atrophy.

BACKGROUND Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM) that severely affects the patients' quality of life. However, the effectiveness of oral phosphodiesterase type 5 inhibitors in these patients is poor. Sphingosine-1-phosphate (S1P) and S1P receptor 2 (S1PR2) are important factors regulating the Rho-kinase pathway, and understanding these factors may provide ideas for new therapeutic strategies for ED. OBJECTIVES To investigate whether the S1PR2 receptor antagonist JTE-013 could improve DM-induced ED (DMED) in rats and to explore the potential mechanisms. MATERIALS AND METHODS We used 50 male Sprague Dawley rats (8 weeks old) for this experiment. Type Ⅰ DM was induced in forty-two rats via streptozotocin administration; the rest of the rats served as controls. Eight weeks after DM induction, rats with ED were selected via an apomorphine test. Eight of them were injected intraperitoneally with JTE-013 each day for 4 weeks. The rest were fed under the same conditions for 4 weeks. Erectile function was measured by cavernous nerve electrostimulation. The expression levels of related signaling pathways were evaluated using Western blotting, real-time PCR, and immunohistochemistry. RESULTS Erectile function was significantly impaired in the DMED group compared with the control group and was partially improved in the DMED + JTE-013 group. The expression of S1PR2 and the activity of the RhoA/ROCK/phospho-myosin phosphatase target subunit 1 (p-MYPT1) pathway proteins were higher in the DMED group than in the other two groups, and JTE-013 treatment significantly reduced the expression/activity of these proteins. Furthermore, the DMED group showed severe corporal fibrosis, a higher apoptotic index and increased activity in the TGF-β1/LIMK2/Cofilin pathway compared with the control group. JTE-013 supplementation significantly ameliorated these pathological changes. DISCUSSION AND CONCLUSION JTE-013 supplementation partially improved erectile function in rats with DMED, likely by inhibiting smooth muscle contraction, corporal fibrosis, and apoptosis.

The aim of the study was to investigate how testosterone regulating endothelial function in the corpus cavernosum of rats. A total of 32 male Sprague-Dawley (SD) rats, 10-weeks-old, were divided randomly into four groups: normal control group (Control); castration group (Castration); the other 16 rats were castrated followed by testosterone supplementation (orally) every day for 8 weeks: castration +10 mg/kg (lower dose) testosterone group (Castration +LT) and castration +20 mg/kg (high dose) testosterone group (Castration +HT). The data showed that androgen deficiency in the Castration group could induce oxidative stress to attenuate endothelial function, manifested by the impairment of endothelial intercellular junction and endothelial content. This was in parallel with a significant decrease in Akt, Akt target and FOXO3a phosphorylation. Testosterone supplementation in the Castration +LT and Castration +HT groups could greatly preserve testosterone serum levels, endothelial function and erectile function through activation of sphingosine-1-phosphate receptor 1 (S1P1)/Akt/FOXO3a pathway. Together, this study suggested that S1P1/Akt/FOXO3a pathway was involved in endothelial dysfunction in the context of androgen deficiency and oxidative stress, which might further explain the mechanism of androgen deficiency inducing ED.

Machine learning (ML) is one of the main methods to address the problem of big data mining. ML can enable the e-commerce system upon self-innovate and improvement by accumulating prior knowledge. The big data produced by transaction, interaction and observation from e-commerce enterprises can greatly provide decision-making service for marketing strategy. In this paper we take the e-commerce data of tea-device enterprise as an example, use the FP-grow algorithm to get the frequent item sets, so as to mining and analyze association rule of user behavior to get feature vector as the basis of user classification, then use Naive Bayesian algorithm on the feature vector to implement clustering learning for precision marketing and personalized online referral services. Finally, we evaluate the feasibility of big data mining with ML through the profit produced by the sale of goods. Experimental results show that ML can not only greatly improve the performance in big data mining, can also achieve precise marketing, and can further increasing about 20% marginal profit for each type of goods.

To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment.We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15).The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either.Hypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.目的： 分析鞍区占位病变继发男性性腺功能减退症的临床特点，探索其病因，提高其诊治水平。 方法： 通过回顾22例鞍区占位病变继发男性性腺功能减退症患者的临床资料，结合文献，分析该病的临床表现、发生原因和治疗原则。22例患者术前出现性腺功能减退症者为A组，术后及放疗后出现者为B组。按内分泌治疗药物分为Andriol组和hCG组。 结果： A组患者鞍区占位平均径线［(2.35±0.71) cm］显著大于B组［(1.83±0.36) cm］（P0.05），泌乳素腺瘤的发生率A组也显著高于B组（60%vs 0，P0.01）。B组患者接受手术及放疗后，黄体生成素（LH）、卵泡刺激素（FSH）、睾酮（T）水平均明显下降（P均0.01）。使用十一酸睾酮胶丸和hCG治疗后，Andriol组和hCG组患者T、国际勃起功能指数-5(IIEF-5)评分均较术前明显提高［T，Andriol组：(9.40±2.43) nmol/L vs (2.71±1.39) nmol/L，hCG组：(10.65±2.32) nmol/L vs (3.23±1.53) nmol/L；IIEF-5，Andriol组：(14.50±3.62)分 vs (5.00±2.61)分，hCG组：(15.07±3.27)分 vs (5.36±1.82)分］（P均0.01）；其中以发育迟缓就诊的患者治疗后出现睾丸增大、阴毛生长等青春期发育征象。hCG组睾丸体积明显增大（P0.01），并有7例产生精子，产生精子者其睾丸初始体积［(11.5 ± 2.3) ml］明显大于未产生精子者［(7.5 ± 2.3) ml］（P0.01）。Andriol组治疗前后睾丸体积无统计学差异，无产生精子的患者。 结论： 手术和放疗对垂体组织的损伤、病变的占位性效应和高泌乳素血症是鞍区占位性病变引起性腺功能减退的可能原因。十一酸睾酮和hCG均可明显提高T水平和改善勃起功能障碍的症状。十一酸睾酮胶丸治疗对精子生成无治疗效应。.

Metabolic syndrome (MetS) is a risk factor for erectile dysfunction (ED), but the underlying mechanisms are unclear. The aims of this study were to determine the underlying mechanisms of metabolic syndrome-related ED (MED). Sprague Dawley (SD) rats were fed a high-fat diet for 6 months, and metabolic parameters were then assessed. An apomorphine test was conducted to confirm MED. Only rats with MED were administered an intracavernosal injection of either epidermal growth factor (EGF) or vehicle for 4 weeks. Erectile responses were evaluated by determining the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP). Levels of protein expression were examined by western blotting and immunohistochemistry. Body weight, fasting blood glucose, plasma insulin and plasma total cholesterol were increased in the MetS rats compared with those in control rats (each p

Shallow lakes are vulnerable to eutrophication because of abundant phytoplankton and significant nutrient input from sediments. Previous studies have researched the effect of environmental factors on phytoplankton and phosphorus release from sediment. However, few studies have simultaneously evaluated the interactive effects of environmental factors on phytoplankton communities and the interactions among different sediment nutrients. This paper reports on a 2016 investigation that examined the phytoplankton community and physical and chemical factors in both the water column and sediments in a Chinese shallow lake and its adjoining rivers. Our results indicated that rivers with water gates and lake areas had greater Chlorophyll a concentrations (Chl a) than natural rivers with similar total phosphorus (TP) concentrations; this indicates the importance of residence time on phytoplankton biomass. Although temperature impacted Chl a less than nutrients, its effects were highly species-specific, modulating relationships between nutrients and the abundance of different phytoplankton taxa. The effects of nutrients changed based on phytoplankton biomass and community composition, suggesting that different phytoplankton taxa have different nutrient demands. We predict that increasing residence time, temperature, and nutrients will increase phytoplankton biomass and increase the future dominance of Chlorophyta and Cyanophyta. In the interstitial water, there were no significant seasonal differences in TP, total nitrogen, and soluble reactive silica concentrations. However, ammonia concentrations were higher in the spring and lower in other seasons; nitrate and sulfate were abundant when the ammonia concentration was low. The total iron level in sediments was significantly negatively related with TP at low ammonia and silica concentrations and at high nitrate and sulfate concentrations in the interstitial water. These results indicated that nutrients are closely coupled in the sediments, highlighting the importance of oxidation-reduction potentials on internal nutrient balance.

A meta-analysis was performed to evaluate the efficacy of local anesthesia in alleviating pain during prostate biopsy. We searched relevant articles in PubMed and Embase. The included studies should be randomized controlled trials (RCT) using local anesthesia to alleviate pain during biopsy, which was recorded by a pain scale. Analgesic efficacy of different local anesthesia techniques were analyzed, including intrarectal local anesthesia (IRLA), periprostatic nerve block (PNB), pelvic plexus block (PPB) and intraprostatic local anesthesia (IPLA). We included 46 RCTs. PNB significantly reduced pain score compared with placebo (−1.27 [95% confidence interval [95% CI] −1.72, −0.82]) or no injection (−1.01 [95% CI −1.2, −0.82]). IRLA with prilocaine-lidocaine cream could also reduced pain (−0.45 [95% CI −0.76, −0.15]), while the IRLA with lidocaine gel was not effective (−0.1 [95% CI −0.24, 0.04]). PNB lateral to the neurovascular bundle had better analgesic effect than at prostate apex (P = 0.02). Combination use of PPB and IRLA considerably alleviated pain of patients compared with the combination of PNB and IRLA (−1.32 [95% CI −1.59, −1.06]). In conclusion, local anesthesia could alleviate patients’ pain during the prostate biopsy. PNB was not so effective as PPB.

Our previous studies had reported that Human Tissue Kallikrein 1 (hKLK1) preserved erectile function in aged transgenic rats, while the detailed mechanism of hKLK1 protecting erectile function in aged rats through activation of cGMP and cAMP was not mentioned. To explore the latent mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring the hKLK1 gene (TGR) were fed to 4 and 18 months old and divided into four groups: young WTR (yWTR) as the control, aged WTR (aWTR), aged TGR (aTGR) and aged TGRs with HOE140 (aTGRH). Erectile function of all rats was evaluated by cavernous nerve electrostimulation method and measured by the ratio of intracavernous pressure/ mean arterial pressure (ICP/MAP) in rats. Expression levels of cAMP and cGMP were assessed, and related signaling pathways were detected by western blot, immunohistochemistry and RT-PCR. Our experiment results showed erectile function of the aWTR group and aTGRH group was lower compared with those of other two groups. Also, expression levels of cAMP and cGMP were significantly lower than those of other two groups. Moreover, expressions of related signaling pathways including DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP were also downregulated in the corpus cavernosum of rats in aWTR group. Our finding revealed hKLK1 played a protective role in age-related ED. The DDAH/ADMA/NOS/cGMP and COX-2/PTGIS/cAMP pathways that were linked to the mechanism hKLK1 could increase the levels of cGMP and cAMP, which might provide novel therapy targets for age-related ED.

Background To investigate the role of human tissue kallikrein 1 (hKLK1) gene on the erectile dysfunction (ED) of induced by hyperhomocysteinaemia (HHcy) in rats. Methods The HHcy rat model was formed by a methionine (Met)-rich diet in SD rats. Here, 32 rats, 10-week-age, were divided in four groups: control (n=8), low-dose (4% Met; n=8), high-dose (7% Met; n=8) and transgenic rats (TGR +7% Met; n=8). Thirty days later, erectile function and related targets were tested. Results ED, impaired endothelial and smooth muscle function, and pathological changes (a higher apoptosis level and a lower autophagy level) were showed in the 4% Met and 7% Met groups compared with the control, while were all markedly diminished by the hKLK1 gene in the TGR +7% Met group. Conclusions These data suggested that hKLK1 might play an inhibition role on HHcy-induced ED in rats by protection of endothelial function and inhibition of oxidative stress and corporal fibrosis.

Background To investigate whether FTY720, approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis, could ameliorate erectile dysfunction induced by diabetes mellitus (DMED). Methods Thirty-two Sprague-Dawley rats (8 weeks old) were induced type I DM and the other eight rats formed the control (n=8). Eight weeks later, 17 rats with DMED tested with an apomorphine test were divided in two groups: DMED (n=8) and DMED + FTY720 (1 mg/kg/d; n=9). Treatment of FTY720 lasted for 4 weeks. Results Impaired erectile function, inhibited S1P3/Akt/NO/cGMP activity, serious corporal fibrosis and over-activated pathways (the Smad and non-Smad) were found in the DMED group compared with the control, while FTY720 partly but significantly improved these pathological changes induced by DM. Conclusions FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED.

Diabetes is a risk factor for erectile dysfunction (ED). The proposed mechanisms responsible for diabetic ED are associated with an increase in reactive oxygen species (ROS) production, overactivity of RhoA/ROCK signaling pathway and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as seen in experimental models of diabetic rats.The aim of this study was to investigate whether NADPH oxidase inhibitor apocynin can ameliorate Streptozotocin (STZ)-induced diabetes-related ED by reducing the ROS production and inhibiting the activity of RhoA/ROCK signaling pathway.The diabetic rats were treated with and without the NADPH oxidase inhibitor apocynin.Erectile responses were evaluated by determining mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) with electrical stimulation of the cavernous nerve. Levels of mRNA expression were measured by real-time polymerase chain reaction (RT-PCR). Levels of protein expression were examined by Western Blot. ROS production was measured by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances assay.The ratio of Maximum ICP-to-MAP (MaxICP/MAP) was significantly decreased in diabetic ED rats, compared to that of age-matched control rats (P0.05). Apocynin improved erectile function of diabetic rats (P0.05). Expression levels of RhoA (cytosol), nNOS and eNOS were reduced, compared to those of control rats (P0.05). Apocynin significantly elevated their expression levels in diabetic rats (P0.05). Expression levels of ROCK1, RhoA (membrane fraction), p-MYPT1 and NADPH oxidase subunits p47(phox) and p67(phox) were increased in diabetic rats when compared to those of control rats (P0.05), and it was observed that apocynin significantly reduced their expression levels in diabetic rats (P0.05). ROS production was increased in diabetic rats when compared to that of control rats (P0.05), the effect of apocynin was a reduction in the ROS production in diabetic rats (P0.05).NADPH oxidase inhibitor apocynin can ameliorate diabetes-related ED by reducing the ROS production and inhibiting the activity of RhoA/ROCK signaling pathway.

Summary Men with hyperlipidemia are more likely to have erectile dysfunction (ED) than those without hyperlipidemia, but the mechanisms are not fully understood. The aim of this study was to investigate the underlying mechanism of ED caused by hyperlipidemia. Fourteen 8-week-old Sprague–Dawley rats were randomly divided into two groups: a control group and a hyperlipidemia group (fed chow containing 4% cholesterol and 1% cholic acid). After 6 months, we assessed erectile function by performing cavernous nerve electrostimulation followed by intracavernosal pressure/mean arterial pressure measurements, as well as plasma lipid profile assessment in all rats. A transferase-mediated nick end labeling (TUNEL) assay, immunohistochemical staining and Western blotting were performed to determine the levels of apoptosis, autophagy and fibrosis in the penile tissue. Compared with the control group, the hyperlipidemia group exhibited: (i) increased plasma lipid levels; (ii) decreased erectile function; (iii) a decreased smooth muscle/collagen ratio; (iv) increased fibrosis; (v) increased apoptosis and decreased autophagy. Overall, hyperlipidemia may attenuate erectile function in rats by causing of cavernosal fibrosis.

Testosterone is overwhelmingly important in regulating erectile physiology. However, the associated molecular mechanisms are poorly understood. The purpose of this study was to explore the effects and mechanisms of testosterone in erectile dysfunction (ED) in castrated rats. Forty male Sprague-Dawley rats were randomized to four groups (control, sham-operated, castration and castration-with-testosterone-replacement). Reactive oxygen species (ROS) production was measured by dihydroethidium (DHE) staining. Erectile function was assessed by the recording of intracavernous pressure (ICP) and mean arterial blood pressure (MAP). Protein expression levels were examined by western blotting. We found that castration reduced erectile function and that testosterone restored it. Nitric oxide synthase (NOS) activity was decrease in the castrated rats, and testosterone administration attenuated this decrease (eachp< 0.05). The testosterone, dihydrotestosterone, cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) concentrations were lower in the castrated rats, and testosterone restored these levels (eachp< 0.05). Furthermore, the cyclooxygenase-2 (COX-2) and prostacyclin synthase (PTGIS) expression levels and phospho-endothelial nitric oxide synthase (p-eNOS, Ser1177)/endothelial nitric oxide synthase (eNOS) ratio were reduced in the castrated rats compared with the controls (eachp< 0.05). In addition, thep40phoxandp67phoxexpression levels were increased in the castrated rats, and testosterone reversed these changes (eachp< 0.05). Overall, our results demonstrate that testosterone ameliorates ED after castration by reducing ROS production and increasing the activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

To investigate the role of the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway in erectile dysfunction (ED) caused by the absence of testosterone (T).We randomly divided 30 eight-week-old healthy male SD rats into groups A (control) , B (castration), and C (castration + androgen replacement). The rats in groups B and C were castrated surgically, and those in C injected with T undecanoate (100 mg/kg) at 1 week after castration, while the others with 0.9% normal saline instead. At 1 month after treatment, we determined the serum T level, intracavernous pressure (ICP), and mean carotid arterial pressure (MAP) of the rats, and detected the expressions of ERK1/2 and endothelial nitric oxide synthase (eNOS) by Western blot.The serum T level was significantly lower in group B ([1.27 ± 0.48] nmol/L) than in A ([17.14 ± 1.07] nmol/L) and C ([16.24 ± 1.90] nmol/L) (P0.05), and so were ICP and MAP (P0.05). The expression of ERK1/2 showed no statistically significant differences among the three groups (P0.05), that of phosphatase ERK1/2 was markedly higher while that of eNOS remarkably lower in group B than in A and C (both P0.05).Androgen replacement may improve the erectile function of castrated rats by regulating the ERK1/2 pathway.

Objective To investigate the mechanism of androgen replacement therapy (ART) improving erectile dysfunction (ED) in castrated rats. Methods We randomly divided 40 8-week-old healthy male SD rats into 4 groups: group A was the control, and rats of the group B, C and D were castrated, then rats in the groups C and D were treated with different concentrations of testosterone undecanoate orally every day (C: 10 mg/kg, D: 20 mg/kg), while other groups with 0.9% NS instead. 8weeks’ treatment later, we determined the level of serum testosterone and assessed the erectile function of rats. Western blot, immunohistochemistry were performed to detect the level of target proteins. Results (I) The level of serum testosterone and erectile function (Max ICP/MAP): group Bwas significantly lower than group A, C and D, and group D was higher compared with group C; (II) effect of castration and ART on endothelial cells and androgen receptor (AR)/vascular endothelial growth factor (VEGF)/cyclin A pathway: the expression of CD31, vWF and AR/VEGF/cyclin A in group B were lower than group A, C and D, and group D was higher compared with group C; (III) effect of castration and ART on corpus cavernosum smooth muscle cells (CCSMCs) and TGF-β/S1P2/RhoA/ROCK pathway: the expression of α-sma in group B were lower than group A, C and D, and group D was higher compared with group C; while the expression of TGF-β/S1P2/RhoA/ROCK1 were higher in group B than group A, C and D, and group D was lower compared with group C. Conclusions ART can improve ED in castrated rats through promoting the proliferation of corpus cavernosum endothelial cells by activating AR/VEGF/cyclin A pathway; decreasing the contraction of CCSMCs and corporal fibrosis by inhibiting TGF-β/S1P2/RhoA/ROCK pathway, which provides reference for revealing the mechanism of ART treating ED associated late-onset hypogonadism.

Objective For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. The aim of this study was to investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Methods Type 1 diabetes mellitus was induced in male rats using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for four weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for four weeks. Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Results Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was ameliorated in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway–related proteins was reduced. Taurine supplementation restored erectile response as well as histologic and molecular alterations. Conclusions Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED.

Objective To investigate the presence, location and functional role of TMEM16A/anotamin-1 (Ano1) calcium-activated chloride channel (CaCC) in the penile of rats with diabetic erectile dysfunction. Methods Eight-week-old male Sprague-Dawley (SD) rats were administrated streptozotocin (diabetic) or citrate buffer (control) randomly. Erectile function was measured by cavernous nerve electrostimulation at 12th week after diabetes was induced. The effect of Ano1 specific inhibitor—T16Ainh-A01 on intracavernous pressure (ICP) was evaluated. Then the penile tissues were harvested for molecular exploration. Real-time PCR and Western Blotting were used to assess the expression of Ano1 in penile tissues. Immunofluorescent labelling of penile tissue allowed localization of Ano1. Cavernous smooth muscle cell (CSMC) was cultured in high glucose medium. The change of Ano1 was measured using Western Blotting. The proliferation of CSMC was evaluated by cell counting kit-8 (CCK-8). Results Erectile function was impaired in diabetic rats. The expression of Ano1 was increased in rats with diabetic erectile dysfunction at mRNA and protein levels. Immunofluorescent labelling revealed the presence of Ano1 mainly in cavernous smooth muscle cells. The inhibition of Ano1 increased the ICP of DED rats. High glucose in vitro enhanced the proliferation of CSMC and the expression level of Ano1. Conclusions Ano1 is expressed in rat penile tissue and is increased with diabetes mellitus. The inhibition of Ano1 increased the ICP of DED rats. The alerted Ano1 may be associated with diabetic erectile dysfunction. It is a potential therapy target for ED in the future.

Summary Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.

Although some genes that cause Kallmann syndrome (KS) have been identified by traditional linkage analysis and candidate gene techniques, the syndrome's molecular etiology in the majority of patients remains poorly understood. In this paper, we present the clinical assessments of a consanguineous Han Chinese family with three KS descendants. To understand the molecular etiology of KS from a genome-wide perspective, we investigated the genome-wide profile of structural variation in this family using the Affymetrix Genome-Wide Human SNP Array 6.0 platform. The results revealed that the three affected individuals had common copy number variants (microdeletions) on chromosomes 1p21.1, 2q32.2, 8q21.13, 14q21.2 and Xp22.31. Moreover, the copy number variants on Xp22.31 were located in the intron of KAL1, which causes X-linked KS. Two PCR assays were performed on these regions to validate the results obtained using the chips. In addition, genomic microdeletions in this region were verified in one of 29 Han Chinese sporadic KS cases and one of four other family cases, but not in 26 Han Chinese sporadic normosmic idiopathic hypogonadotropic hypogonadism cases and 100 unrelated Han Chinese normal controls. Our results provide a novel insight into the relative contributions of certain copy number variants to KS's molecular etiology and generate a list of interesting candidate regions for further studies.

Introduction For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. Aim To investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Methods Type 1 diabetes mellitus was induced in male rats by using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for 4 weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for 4 weeks. Main Outcome Measures Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Results Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was improved in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway–related proteins was reduced. Taurine supplementation ameliorated erectile response as well as histologic and molecular alterations. Conclusion Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED.

The purpose of this paper is to investigate a higher-order nonlinear Schrödinger equation with non-Kerr term by using the bifurcation theory method of dynamical systems and to provide its bounded traveling wave solutions. Applying the theory, we discuss the bifurcation of phase portraits and investigate the relation between the bounded orbit of the traveling wave system and the energy level. Through the research, new traveling wave solutions are given, which include solitary wave solutions, kink wave solutions, and periodic wave solutions.