Monotropein Protects Mesenchymal Stem Cells from Lipopolysaccharide-Induced Impairments and Promotes Fracture Healing in an Ovariectomized Mouse Model.

Monotropein is one of the active ingredients in Morinda Officinalis, which has been used for the treatment in multiple bone and joint diseases. This study aimed to observe the in vitro effects of Monotropein on osteogenic differentiation of lipopolysaccharide treated bone marrow mesenchymal stem cells (bMSCs), and the in vivo effects of local application of Monotropein on bone fracture healing in ovariectomized mice. Lipopolysaccharide was used to set up the inflammatory model in bMSCs, which were treated by Monotropein. Molecular docking analysis was performed to evaluate the potential interaction between Monotropein and p65. Transverse fractures of middle tibias were established in ovariectomized mice, and Monotropein was locally applied to the fracture site using injectable hydrogel. Monotropein enhanced the ability of primary bMSCs in chondro-osteogenic differentiation. Furthermore, Monotropein rescued lipopolysaccharide-induced osteogenic differentiation impairment and inhibited lipopolysaccharide-induced p65 phosphorylation in primary bMSCs. Docking analysis showed that the binding activity of Monotropein and p65/14-3-3 complex is stronger than the selective inhibitor of NF-κB (p65), DP-005. Local application of Monotropein partially rescued the decreased bone mass and biomechanical properties of callus or healed tibias in ovariectomized mice. The expressions of Runx2, Osterix and Collagen I in the 2-week callus were partially restored in Monotropein-treated ovariectomized mice. Taking together, local application of Monotropein promoted fracture healing in ovariectomized mice. Inhibition of p65 phosphorylation and enhancement in osteogenesis of mesenchymal stem cells could be partial of the effective mechanisms.

Comprehensive analysis of FRAS1/FREM family as potential biomarkers and therapeutic targets in renal clear cell carcinoma.

Background: FRAS1 (Fraser syndrome protein 1), together with FREM1 (the Fras1-related extracellular matrix proteins 1) and FREM2, belonging to the FRAS1/FREM extracellular matrix protein family, are considered to play essential roles in renal organogenesis and cancer progression. However, their roles in kidney renal clear cell carcinoma (KIRC) remain to be elucidated. Methods: FRAS1/FREM RNA expression analysis was performed using TCGA/GTEx databases, and valided using GEO databases and real-time PCR. Protein expression was peformed using CPTAC databases. Herein, we employed an array of bioinformatics methods and online databases to explore the potential oncogenic roles of FRAS1/FREM in KIRC. Results: We found that FRAS1, FREM1 and FREM2 genes and proteins expression levels were significantly decreased in KIRC tissues than in normal tissues. Decreased FRAS1/FREM expression levels were significantly associated with advanced clinicopathological parameters (pathological stage, grade and tumor metastasis status). Notably, the patients with decreased FRAS1/FREM2 expression showed a high propensity for metastasis and poor prognosis. FRAS1/FREM were correlated with various immune infiltrating cells, especially CD4+ T cells and its corresponding subsets (Th1, Th2, Tfh and Tregs). FRAS1 and FREM2 had association with DNA methylation and their single CpG methylation levels were associated with prognosis. Moreover, FRAS1/FREM might exert antitumor effects by functioning in key oncogenic signalling pathways and metabolic pathways. Drug sensitivity analysis indicated that high FRAS1 and FREM2 expression can be a reliable predictor of targeted therapeutic drug response, highlighting the potential as anticancer drug targets. Conclusion: Together, our results indicated that FRAS1/FREM family members could be potential therapeutic targets and valuable prognostic biomarkers of KIRC.

Significance of hyperhomocysteinaemia as an effective marker for vasculogenic erectile dysfunction: a cross-sectional study.

Background: The primary objective of this cross-sectional study aimed at evaluating serum levels of homocysteinemia (Hcy) in a cohort of erectile dysfunction (ED) patients, and at assessing the correlation between Hcy and vasculogenic ED. Methods: A total of 119 Chinese patients presenting with ED [International Index of Erectile Function (IIEF)-5≤21] were enrolled in this study. The whole cohort was asked to complete the IIEF-5 questionnaire and blood analysis. A detailed medical history, physical examination, nocturnal penile tumescence (NPT) tests and penile color Doppler ultrasonography (pDUS) were performed by a urologist. Based on the pDUS result, they were further categorized into 2 main groups: non-vasculogenic ED (n=79) and vasculogenic ED (n=40). Results: Age and Hcy levels were significantly higher in the vasculogenic ED group compared to the non-vasculogenic ED group (38.45±8.51 vs. 32.29±7.57 and 22.91±5.85 vs. 16.31±5.23 µmol/L, respectively, P<0.01). Univariate and multivariable regression analyses showed that the incidence of vasculogenic ED raised significantly with the increase of Hcy level. After multivariable adjustment, ED patients with hyperhomocysteinaemia (HHcy) had 13.42 times the odds of vasculogenic ED compared with patients without HHcy (OR: 13.42, 95% CI: 3.78 to 47.64). Moreover, the risk of vasculogenic ED was 1.24 (95% CI: 1.04 to 1.48, P=0.01) per-unit increase in Hyc concentration for ED with HHcy. In addition, the smoothing curve revealed that Hcy levels were inversely correlated with peak-systolic velocity (PSV) (ß: -0.48, 95% CI: -0.91 to -0.05, P=0.04) in vasculogenic ED patients by multivariate regression analysis. Furthermore, in the analysis of receiver operating characteristic curve, the area under curve for Hcy to predict vasculogenic ED was 0.81 (95% CI: 0.73 to 89) in patients with ED. Conclusions: These findings suggest a dose-dependent association between Hcy and vasculogenic ED. HHcy was a risk factor for vasculogenic erectile dysfunction. Therefore, HHcy is likely to be a potential indicator to predict and diagnose vasculogenic ED when using pDUS.

Identification of immune-related genes that predict prognosis and risk of bladder cancer: bioinformatics analysis of TCGA database.

BACKGROUND: Bladder cancer (BLCA) is the major tumor of the urinary system, and immune-related genes (IRGs) contribute significantly to its initiation and prognosis. RESULTS: A total of 51 prognostic IRGs significantly associated with overall survival were identified. Functional enrichment analysis revealed that these genes were actively involved in tumor-related functions and pathways. Using multivariate Cox regression analysis, we detected 11 optimal IRGs (ADIPOQ, PPY, NAMPT, TAP1, AHNAK, OLR1, PDGFRA, IL34, MMP9, RAC3, and SH3BP2). We validated the prognostic value of this signature in two validation cohorts: GSE13507 (n = 165) and GSE32894 (n = 224). Furthermore, we performed a western blot and found that the expression of these IRGs matched their mRNA expression in TCGA. Moreover, correlations between risk score and immune-cell infiltration indicated that the prognostic signature reflected infiltration by several types of immune cells. CONCLUSION: We identified and validated an 11-IRG-based risk signature that may be a reliable tool to evaluate the prognosis of BLCA patients and help to devise individualized immunotherapies. METHODS: Bioinformatics analysis was performed using TCGA and ImmPort databases. Cox regression was used to identify prognostic signatures. Two external GEO cohorts and western blotting of samples were performed to validate the IRG signature.

Generation of an iPSC line (HRMSDUi001-A) from an azoospermic patient with 45,XY,der(13;14)(q10;q10) karyotype.

Robertsonian translocation between chromosomes 13 and 14 is reported to be a cause of male infertility. Here, we established an iPSC line (HRMSDUi001-A) from an azoospermic patient with 45,XY,der(13;14)(q10;q10) karyotype. Peripheral blood mononuclear cells were reprogrammed to generate hiPSCs by non-integrating delivery of OCT4, SOX2, KFL4 and MYC. The iPSC line expressed pluripotency markers, could differentiate into cells of three germ layers in vitro, and carried 45,XY,der(13;14)(q10;q10) karyotype.

TRPM3 channel activation inhibits contraction of the isolated human ureter via CGRP released from sensory nerves.

AIMS: Sensory nerve activation modulates ureteral contractility by releasing neuropeptides including CGRP and neurokinin A (NKA). TRPM3 is a recently discovered thermosensitive channel expressed in nociceptive sensory neurons, and plays a key role in heat nociception and chronic pain. The aim of this study is to examine the role of TRPM3 activation in human ureter motility. MAIN METHOD: Human proximal ureters were obtained from fourteen patients undergoing nephrectomy. Spontaneous or NKA-evoked contractions of longitudinal ureter strips were recorded in an organ bath. Ureteral TRPM3 expression was examined by immunofluorescence. KEY FINDINGS: Spontaneous contractions were observed in 60% of examined strips. TRPM3 activation using pregnenolone sulphate (PS) or CIM0216 (specific TRPM3 agonists) dose-dependently reduced the frequency of spontaneous and NKA-evoked contractions, with IC50s of 241.7 µM and 4.4 µM, respectively. The inhibitory actions of TRPM3 agonists were mimicked by CGRP (10 to 100 nM) or a cAMP analogue (8-Br-cAMP; 1 mM). The inhibitory actions of TRPM3 agonists (300 µM PS or 30 µM CIM0216) were blocked by pretreatment with primidone (TRPM3 antagonist; 30 µM), tetrodotoxin (sodium channel blocker; 1 µM), olcegepant (CGRP receptor antagonist; 10 µM), or H89 (non-specific PKA inhibitor; 30 µM). TRPM3 was co-expressed with CGRP in nerves in the sub-urothelial and intermuscular regions of the ureter. SIGNIFICANCE: TRPM3 channels expressed on sensory terminals of the human ureter involve in inhibitory sensory neurotransmission and modulate ureter motility via the CGRP-cAMP-PKA signal pathway. Targeting TRPM3 may be a pharmacological strategy for promoting the ureter stone passage.

Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort.

BACKGROUND: Since SARS-CoV-2 infection was first identified in December 2019, the novel coronavirus-induced pneumonia COVID-19 spread rapidly and triggered a global pandemic. Recent bioinformatics evidence suggested that angiotensin-converting enzyme 2-the main cell entry target of SARS-CoV-2-was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection. OBJECTIVES: To identify SARS-CoV-2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection. METHODS: From February 26 to April 2, 2020, 23 male patients with COVID-19 were recruited. The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail. We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS-CoV-2 infection using approved methods. RESULTS: The age range of the 23 patients was 20-62 years. All patients tested negative for SARS-CoV-2 RNA in semen specimens. Among them, the virus had been cleared in 11 patients, as they tested negative. The remaining 12 patients tested negative for SARS-CoV-2 RNA in semen samples, but were positive in sputum and fecal specimens. The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts, and sperm morphology of the patients were within normal ranges. DISCUSSION AND CONCLUSION: In this cohort of patients with a recent infection or recovering from COVID-19, there was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection.

Transparent Nano Thin-Film Transistors for Medical Sensors, OLED and Display Applications.

BACKGROUND: Transparent thin-film transistors (TFTs) have received a great deal of attention for medical sensors, OLED and medical display applications. Moreover, ultrathin nanomaterial layers are favored due to their more compact design architectures. METHODS: Here, transparent TFTs are proposed and were investigated under different stress conditions such as temperature and biases. RESULTS: Key electrical characteristics of the sensors, such as threshold voltage changes, illustrate their linear dependence on temperature with a suitable recovery, suggesting the potential of the devices to serve as medical temperature sensors. The temperature conditions changed in the range of 28°C to 40°C, which is within the standard human temperature testing range. The thickness of the indium-gallium-zinc oxide semiconductor layer was as thin as only 5-6 nm, deposited by mature radio-frequency sputtering which also showed good repeatability. Optimal bending durability caused by mechanical deformation was demonstrated via suitable electrical properties after up to 600 bending cycles, and by testing the flexible device at a different bending radii ranging from 48 mm to 18 mm. CONCLUSION: In summary, this study suggests that the present transparent nano TFTs are promising candidates for medical sensors, OLED and displays which require transparency and stability.

Significance of blood lipid parameters as effective markers for arteriogenic erectile dysfunction.

OBJECTIVES: The aim of the study was to investigate the ability of the blood lipid parameters to predict the discrimination of arteriogenic erectile dysfunction (ED). MATERIALS AND METHODS: 260 subjects with ED and 60 healthy controls were enrolled. Eight lipid parameters, including total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, non-HDL-C, TC/HDL ratio, TG/HDL ratio, and LDL/HDL ratio, together with other plasma biomarkers like sex hormones were measured in all participants. Nocturnal penile tumescence (NPT), penile color Doppler ultrasonography (pDUS), and neurophysiological tests were conducted in the ED group. RESULTS: Forty-four ED patients with normal NPT, and 84 with normal vasculature or mixed vascular abnormalities were excluded. The remaining 132 men were classified into two groups, arteriogenic ED (n = 87) and venous leakage (n = 45), by pDUS. TC/HDL, LDL/HDL, and LDL-C were significantly higher (P < .05) and HDL-C was significantly lower (P < .05) in the arteriogenic ED group when compared with the venous and the control groups. Receiver operating characteristic curve analysis identified area under the curve values that were predictive of arteriogenic ED for: TC/HDL and LDL/HDL 0.720 and 0.737, TC/HDL ≥ 3.73 and LDL/HDL ≥ 2.01 (sensitivity: 56.3%; specificity: 83.3% vs sensitivity: 55.2%; specificity: 91.7%), HDL-C (0.791), ≤1.25 mmol/L (sensitivity: 69%; specificity: 81.7%), LDL-C (0.641), ≥2.41 mmol/L (sensitivity: 55.2%; specificity: 76.7%).In the arteriogenic ED group, a significant inverse correlation was detected between TC/HDL, LDL/HDL, LDL-C and 10-minutes peak systolic velocity (PSV) (All P < .01)and a significant positive correlation was recognized between HDL-C and 10-minutes PSV(P < .01). Multivariate step wise linear regression indicated lipid parameters of LDL/HDL and HDL-C were significantly associated with 10-MinPSV (P < .01). CONCLUSION: These findings suggest the LDL/HDL and HDL-C might be a powerful indicator to predict and diagnose arteriogenic ED, and lipid-lowing therapy should be considered for these patients.

Significance of piezo-type mechanosensitive ion channel component 2 in premature ejaculation: An animal study.

BACKGROUND: Penile hypersensitivity is one of the main pathological mechanisms of premature ejaculation. However, little is known about the neurophysiological mechanism of penile peripheral nerve sensitization. Piezo Type Mechanosensitive Ion Channel Component 2 (PIEZO2), was recently identified as a mechanically sensitive channel. OBJECTIVES: This study explored the possible neural mechanisms of PIEZO2 action in the mechanisms of premature ejaculation using molecular biology and electrophysiology approaches. MATERIALS AND METHODS: One hundred seventy male rats and 85 female rats were recruited. The females were induced estrus by injection of estradiol benzoate and progesterone followed by surgically castrated. Subsequently, the copulatory behaviors were record by a video camera six times, once a week. The last three mating processes of 134 male rats were successfully recorded. The males were divided into three groups according to ejaculation frequency value. Immunocytochemical and molecular methods as well as whole-cell patch clamp recording were used to show the difference between premature ejaculation rats and control rats. To further clarify the involvement of PIEZO2 in premature ejaculation, we constructed a PIEZO2 knockdown model in rats by intrathecal injection of PIEZO2 antisense oligodeoxynucleotides. RESULTS: We showed that PIEZO2 in the penis head and in the dorsal root ganglia(DRG) were significantly increased in premature ejaculation rats. Whole-cell patch clamp recording demonstrated that mechanical stimulation evoked a higher inward current density in premature ejaculation rats compared with control rats, which could be inhibited by the PIEZO2-specific antagonist, FM1-43. PIEZO2 knockdown experiments revealed that the inward current density induced by mechanical stimulation was significantly decreased in PIEZO2 knockdown rats, and that the mount frequency and ejaculation latency and frequency were significantly improved in PIEZO2 knockdown rats. DISCUSSION AND CONCLUSION: Our data demonstrate PIEZO2 involvement in peripheral nerve sensitization, indicating that pharmacological antagonism of PIEZO2 may be a useful strategy for treating premature ejaculation.

Real-time transrectal ultrasound-guided seminal vesiculoscopy for the treatment of patients with persistent hematospermia: A single-center, prospective, observational study.

This study aimed to describe endoscopic anatomy of the seminal tract and summarize our experience of transutricular seminal vesiculoscopy (TSV) guided by real-time transrectal ultrasonography (TRUS) in managing persistent hematospermia. A total of 281 consecutive patients with persistent hematospermia who underwent TSV with or without real-time TRUS were enrolled in this single-center, prospective, observational study. The median follow-up period was 36.5 (range: 8.0-97.5) months. TSV was successfully performed in 272 (96.8%) patients. The approach of a 4.5/6 F rigid vesiculoscope entering the seminal tract was categorized into four types on the basis of endoscopic presentation of the ejaculatory duct orifice and verumontanum. Seven (2.6%), 74 (27.2%), 64 (23.5%), and 127 (46.7%) patients had Types I (through the ejaculatory duct in the urethra), II (through the ejaculatory duct in the prostatic utricle), III (transutricular fenestration through a thin membrane), and IV (real-time transrectal ultrasound-guided transutricular fenestration) approach, respectively. In patients who successfully underwent surgery, bleeding occurred in the seminal vesicle in 249 (91.5%) patients. Seminal vesiculitis, calculus in the prostatic utricle, calculus in the ejaculatory duct, calculus in the seminal vesicle, prostatic utricle cysts, and seminal vesicle cysts were observed in 213 (78.3%), 96 (35.3%), 22 (8.1%), 81 (29.8%), 25 (9.2%), and 11 (4.0%) patients, respectively. Hematospermia was alleviated or disappeared in 244 (89.7%) patients 12 months after surgery. Fifteen patients had recurrent hematospermia, and the median time to recurrence was 7.5 (range: 2.0-18.5) months. TSV guided by TRUS may contribute to successful postoperative outcomes in managing persistent hematospermia.

Temperature Dependence Of AOS Thin Film Nano Transistors For Medical Applications.

BACKGROUND: A novel temperature dependent amorphous nano oxide semiconductor (AOS) thin-film transistor (TFT) is reported here for the first time, which is vastly different from conventional behavior. In the literature, the threshold voltage of TFTs decreases with increasing temperature. Here, the threshold voltage increased at higher temperatures, which is different from previously reported results and was repeated on different samples. METHODS: Electrical experiments (such as I-V measurements and photoelectron spectrometer experiments) were performed in order to explain such behavior. Double sweeping gate voltage measurements were performed to investigate the mechanism for the temperature dependent behavior. RESULTS: It was found that there was a change of trap charge under thermal stress, which was released after the stress. CONCLUSION: Non-Arrhenius behaviors (including a linear behavior) were obtained for the amorphous nano oxide thin-film transistors within 303~425 K, suggesting their potential to be adjusted by measurement processes and be applied as temperature sensors for numerous medical applications.

A newly developed transparent and flexible one-transistor memory device using advanced nanomaterials for medical and artificial intelligence applications.

Background: Artificial intelligence (AI) integrated circuits (IC) have memory devices as the key component. Due to more complex algorithms and architectures required by neuroscience and other medical applications, various memory structures have been widely proposed and investigated by involving nanomaterials, such as memristors. Methods: Due to reliability issues of mass production, the dominant memory devices in many computers are still dynamic random access memory (DRAM). A DRAM has one transistor and one capacitor, and so it contains two devices and requires a more compact design to replace. Results: A one-transistor memory device which is more compact than DRAM is proposed. As far as the authors know, this is the first/novel flexible and transparent one-transistor memory device without any additional process to make a typical transistor and which is based on polyvinyl alcohol. By using indium-titanium-oxide (ITO) as the metal gate, PVA as the dielectric layer and In-Ga-Zn-O (IGZO) as the channel, the memory is implemented mainly based on amorphous oxides and transparent flexible nanomaterials. The charge storage for the memory function was investigated here and is attributed to the mechanism of charge trapping between the ITO/IGZO junctions. It shows typical artificial synaptic transmission behaviors such as EPSC (excitatory postsynaptic currents). Conclusion: Such a first flexible and transparent one-transistor memory device based on PVA has one capacitor less than DRAM and could be a potential and promising candidate as an alternative for DRAM, especially in the highly complex AI chips needed for numerous medical applications. The flexible memory nanodevice based on flexible dielectrics such as PVA, which shows typical memory and artificial synaptic behaviors, could also be suitable for portable, flexible, transparent or skin-like medical applications.

Identification of prognostic biomarkers of prostate cancer with long non-coding RNA-mediated competitive endogenous RNA network.

Prostate cancer (PCa) is the second most frequently diagnosed male cancer, and no treatments exist for effective inhibition of metastatic spread of PCa. Long non-coding RNA (lncRNA) plays key roles in pathogenesis and development of various cancers through competing with endogenous RNAs (ceRNAs), but at present research on lncRNA functions in PCa is still very limited. Hence, this aspect was investigated using bioinformatics methods. Firstly, the functional lncRNA-mediated ceRNA network associated with PCa was constructed by the multi-step computational approach. Then the cytoscape software was used to analyze the node degree and betweenness centrality (BC) value of lncRNAs and mRNAs in the interaction. Finally, the lncRNAs were screened in the central region of the network by the node degree and BC value, and the functional enrichment of mRNAs was evaluated with the Gene Ontology (GO) database. In our results, LINC00476, MALAT1, SNHG11, LINC00649, and ILF3-AS1 are the lncRNAs which have the most nodes and higher BC values and considered as prognostic markers in PCa. GO analysis suggested that the function of screened lncRNAs was obviously focused on intracellular receptor signaling pathway, which indicated these lncRNAs might be potential biomarkers for diagnosis, evaluation and gene-targeted therapy of PCa.

Mean platelet volume might be an effective indicator of arterial erectile dysfunction.

The aim of our study was to investigate the role of platelet parameters including mean platelet volume (MPV) and platelet count (PC) in the pathogenesis of penile arteriogenic erectile dysfunction (ED) and to evaluate the association between the platelet parameters and arteriogenic ED. There were 244 patients with ED (based on the International Index of Erectile Function [IIEF]-5 ≤21) and 60 healthy controls (IIEF-5 >21) enrolled. All participants were asked to undergo a laboratory examination, and penile vascular function was evaluated using penile color Doppler ultrasonography (pDUS). Among these ED patients, 24 patients with no abnormality on nocturnal penile tumescence (NPT) and 84 with normal vasculature or mixed vascular abnormalities were excluded. The other patients were classified into three groups as follows: control (n = 60), arteriogenic ED (n = 99), and venous leakage (n = 37) groups. MPV and PC were significantly higher in the arteriogenic ED group compared with the venous and control groups (P < 0.05). Receiver operating characteristic curve analysis revealed that the area under the curve for MPV to predict arteriogenic ED was 0.707. MPV ≥9.65 fl was recognized as a cut-off value for potential arteriogenic ED (sensitivity: 47.5%; specificity: 91.7%). A significant inverse correlation was detected between MPV and 10-min peak systolic velocity (PSV) (r = -0.34; P < 0.001) in the arteriogenic ED group. These findings suggest that the MPV might be a powerful indicator to predict and diagnose arteriogenic ED, and MPV may be a marker for ED when using pDUS.

Significance of penile hypersensitivity in premature ejaculation.

To assess the correlation between penile hypersensitivity and premature ejaculation (PE), a total of 420 consecutive subjects attending our andrologic clinic for suspected PE were enrolled. The entire cohort was asked to complete the self-report intravaginal ejaculation latency time (IELT) by stopwatch. According to the IELT, the subjects were classified into 3 groups. Vibratory thresholds were recorded at the glans penis and penile shaft using a biothesiometer. We found that vibratory thresholds in the glans penis and penile shaft were significantly lower in both mild and severe PE group than in the control group (3.81 ± 0.57 and 3.54 ± 0.43 vs 4.73 ± 0.77 for glans penis p = 0.000; 3.64 ± 0.52 and 3.37 ± 0.50 vs 4.62 ± 0.69 for penile shaft p = 0.002). The vibratory threshold decreased as the disease aggravated. In the mild and severe PE groups, a significant positive correlation was detected between the mean values of IELT and the vibratory thresholds. Furthermore, in the receiver operating characteristics curve analysis, the area under the curve of the glans penis and penile shaft vibratory thresholds predicting severe PE were 0.852 and 0.893 respectively. Our study established a dose-dependent association between penile vibratory threshold and PE. Therefore, the vibratory threshold can serve as a potential marker for predicting the severity of PE.

Transcutaneous electrical stimulation of somatic afferent nerves in the foot relieved symptoms related to postoperative bladder spasms.

BACKGROUND: Bladder spasm is a common side effect of urological surgery. Main treatment modalities include opioids or anticholinergic medication; however, bladder spasms still occur even after these interventions. Recent studies indicate that transcutaneous stimulation of the foot can result in 50% increase in bladder capacity in healthy adults, and inhibit bladder detrusor overactivity in spinal cord injured patients. In this study, we examined the effects of transcutaneous electrical stimulation of the foot on bladder spasms related symptoms. METHODS: Sixty-six male patients who underwent prostate or bladder surgeries due to benign prostatic hyperplasia or bladder diseases were randomly divided into two groups: the control group (n = 36) and the treatment group (n = 30). The control group received the routine postoperative care. The treatment group received daily transcutaneous electrical stimulation of the foot during 3 days after surgery; each time lasted for 60 min. All patients were evaluated by the Visual Analogue Scale for pain sensation, frequency of bladder spasm episodes, and a total score of bladder spasms symptoms. RESULTS: In the control group, the patients with bladder surgery had a higher Visual Analogue Scale score than patients with prostate surgery (P = 0.024). In both treatment and control groups, the Visual Analogue Scale score, spasm frequency, and total score of bladder spasm symptoms decreased from day 1 to day 3 (P <0.001). The Visual Analogue Scale score at day 2, total score of bladder spasm symptoms at day 2 and day 3 were significantly lower in the treatment group than in the control group (P <0.05). CONCLUSION: These results provided preliminary evidence suggesting beneficial effects of stimulating somatic afferent nerves in the foot on postoperative bladder spasms. TRIAL REGISTRATION: The study was registered with Chinese Clinical Trial Registry on June 13 2016 ( http://www.chictr.org.cn/ ) (Identifier: ChiCTR-INR-16008635).

The application of laparoscopic Doppler ultrasound during laparoscopic varicocelectomy in infertile men.

The aim of this study is to evaluate the benefits of laparoscopic Doppler ultrasound (LDU) application during laparoscopic varicocelectomy (LV), and to compare the surgical outcomes and complications between LDU-assisted LV (LDU-LV) and conventional LV for infertile patients with varicoceles; 147 infertile patients were randomly divided into two groups. Operative and postoperative parameters, semen parameters, and the pregnancy rate were compared. There were no differences in baseline demographics. The operative time was significantly longer in LDU-LV group than LV group. The incidence of postoperative hydrocele was 1.4% (1/72) in LDU-LV group versus 10.7% (8/75) in LV group, which showed a significant difference (P < 0.05). However, other surgical outcomes, such as postoperative hospital stay, postoperative recurrence, and testicular atrophy, were similar between the two groups. Sperm concentration and sperm motility were significantly increased in both groups at 3, 6, and 12 months after surgery (P < 0.01), and they were higher in LDU-LV than LV group in 12 months after surgery (34.21 ± 6.36 vs 29.99 ± 6.04 for concentration, P < 0.05; 40.72 ± 8.12 vs 37.31 ± 6.12 for motility, P < 0.05). Sperm morphology was comparable between the two groups. The pregnancy rate showed no significant difference (44.4% of the LDU-LV vs 37.3% of the LV, P > 0.05). In conclusion, compared with LV, LDU-LV could safely and effectively ligate all spermatic veins and preserve spermatic arteries without leading to high varicocele recurrence and postoperative hydrocele. Given the benefits that sperm counts as well as sperm motility favoring LDU-LV, we recommend that LDU should be routinely used as an effective tool to improve outcomes and safety of laparoscopic varicocelectomy.

Suppression of LASP-1 attenuates the carcinogenesis of prostatic cancer cell lines: Key role of the NF-κB pathway.

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among males worldwide and causes a considerable number of deaths each year. One of the newly explored targets for the development of therapies against PCa is LIM and SH3 protein 1 (LASP-1). In the present study, the function of LASP-1 in the oncogenesis and metastasis of PCa was investigated using a series of in vitro experiments. Moreover, the mechanism through which LASP-1 exerted its effect on the carcinogenesis of PCa was also explored. The expression levels of LASP-1 in clinical PCa specimens were determined both at the mRNA and protein levels. Afterwards, the activity of LASP-1 in human PCa cell lines PC3 and DU145 was inhibited using a short hairpin RNA (shRNA) interfering method. The effects of LASP-1 knockdown on the cell growth, apoptosis, cell cycle distribution, migration and invasion were assessed. It was demonstrated that the expression of LASP-1 was significantly higher in the clinical PCa tissues than the level in the corresponding para-carcinoma tissues. Following the knockdown of the LASP-1 gene in human PCa cell lines, the viability, migration and invasion of the cancer cells were decreased. It was also demonstrated that the change in the cell viability and motile ability were associated with an induction of cell apoptosis and G1 phase cell cycle arrest. Based on the results of the detection of the expression of NF-κB-related factors, it was indicated that LASP-1 may affect the carcinogenesis of PCa through a NF-κB inhibition-dependent manner. Although the detailed explanation of the mechanism of LASP-1 in the carcinogenesis of PCa requires further elucidation, the present study highlights the potential of LASP-1 as a promising therapeutic target to ameliorate the oncogenesis and metastasis of PCa.

Spatio-Temporal Pattern and Influencing Factors of Hemorrhagic Fever with Renal Syndrome (HFRS) in Hubei Province (China) between 2005 and 2014.

Hemorrhagic Fever with Renal Syndrome (HFRS) is considered as a globally distributed infectious disease, which results in many deaths annually in Hubei Province, China. The outbreak of HFRS is usually characterized with spatio-temporal heterogeneity and is seasonally distributed. Further, it might also be impacted by the influencing factors such as socio-economic and geographical environment. To better understand and predict the outbreak of HFRS in the Hubei Province, the spatio-temporal pattern and influencing factors were investigated in this study. Moran's I Index value was adopted in spatial global autocorrelation analysis to identify the overall spatio-temporal pattern of HFRS outbreak. Kulldorff scan statistical analysis was performed to further identify the changing trends of the clustering patterns of HFRS outbreak. Spearman's rank correlation analysis was used to explore the possible influencing factors on HFRS epidemics such as climate and geographic. The results demonstrated that HFRS outbreak in Hubei Province decreased from 2005 to 2012 in general while increasing slightly from 2012 to 2014. The spatial and temporal scan statistical analysis indicated that HFRS epidemic was temporally clustered in summer and autumn from 2005 to 2014 except 2008 and 2011. The seasonal epidemic pattern of HFRS in Hubei Province was characterized by a bimodal pattern (March to May and September to November) while peaks often occurring in the spring time. SEOV-type HFRS was presumed to influence more on the total number of HFRS incidence than HTNV-type HFRS do. The average humidity and human population density were the main influencing factors during these years. HFRS outbreaks were more in plains than in other areas of Hubei Province. We did not find that whether the terrain of the wetland (water system) plays a significant role in the outbreak of HFRS incidence. With a better understanding of rodent infection rate, socio-economic status and ecological environment characteristics, this study may help to reduce the outbreak of HFRS disease.