Colorectal cancer metastasis to the thyroid: A case report and review of the literature.

Metastatic thyroid cancer is rare. Here, the case of a patient with colon cancer that metastasized to the thyroid is described. The patient underwent radical rectal cancer surgery in August 2017 and received six cycles of chemotherapy with oxaliplatin and capecitabine postoperatively. On August 4, 2018, the patient was admitted to the hospital due to the discovery of thyroid nodules on ultrasound and carcinoembryonic antigen levels within the normal range. The biopsy from the fine needle aspiration suggested a malignant tumor. The patient underwent radical thyroid cancer surgery. Using intraoperative rapid frozen pathology, medullary carcinoma was diagnosed. Using postoperative routine pathology combined with immunohistochemistry results, thyroid metastasis from colorectal adenocarcinoma was diagnosed. After surgery, the patient regularly visited the outpatient clinic for chemotherapy with capecitabine. As of May 2023, the patient is still alive with no recurrence.

Individual variation in and lateral asymmetry of mouse epididymal draining lymph nodes.

PROBLEM: Draining lymph nodes (LNs) are pivotal sites for maintaining tolerance to self-antigens as well as eliciting immune responses to exogenous antigens. The epididymis is a male reproductive organ with a unique local immune environment. Although mice are the most commonly used laboratory animals for immunology research, there are no detailed descriptions of the anatomical location and function of LNs that drain the epididymis. METHOD OF STUDY: Evans blue labeling was utilized to explore lymphatic drainage of the epididymis in eight- to ten-week-old male C57BL/6 mice. We confirmed the lymphatic drainage of the epididymis in mice using the objective technique of carboxyfluorescein succinimidyl ester (CFSE)-labeled cells. RESULTS: By combined Evans blue labeling and fluorescent labeling, we found that 1) the patterns of epididymal LN drainage are highly heterogeneous between individual mice; 2) the leftside LNs participate in drainage more frequently than the right-side LNs; and 3) epididymal lymphatic drainage bypasses both the paraaortic and renal LNs in some mice. CONCLUSIONS: These data highlighted the need to consider the individual variation in and lateral asymmetry of draining LNs when characterizing the regional immunology of the mouse epididymis.

Periurethral and Intravenous Injections of Adipose-Derived Stem Cells to Promote Local Tissue Recovery in a Rat Model of Stress Urinary Incontinence.

OBJECTIVE: To compare the effects of periurethral and intravenous injection of adipose-derived stem cells (ADSCs) on voiding function and tissue recovery in a stress urinary incontinence (SUI) rat model. METHODS: Sixty-four postpartum rats were randomly allocated to a normal group and the SUI model was established in 48 rats by vagina balloon dilation and bilateral ovariectomy. The SUI rats were randomized into 3 groups and received urethral injection of PBS (SUI group), periurethral injection of ADSCs (PU group), and intravenous injection of ADSCs (IV group) in 10 days after the ovariectomy. After 1, 7, and 14 days, ADSCs were tracked in urethra specimen. The urinary function of the remaining rats was analyzed at day 28, and urethral tissues were harvested for Western blotting and histochemical analyses. RESULTS: Alpha smooth muscle actin, myosin heavy chain, vascular endothelial growth factor, and neurofilament protein expression was increased in the IV and PU groups. Voiding function was also improved, with no significant differences between the IV and PU groups. The cell retention rate in rat urethral tissues was higher in the PU group than that in the IV group. Compared with the IV group, myosin heavy chain, vascular endothelial growth factor, neurofilament and transforming growth factor-ß1 (TGF-ß1)/Smad pathway protein expression levels were significantly higher in the PU group, while alpha smooth muscle actin expression was significantly lower (P < .05). CONCLUSION: Periurethral and intravenous injection of ADSCs induces different degrees of recovery of the urethral sphincter, cytokine secretion levels and cell retention rates in the urethral tissues in SUI rats, however, there was no significant difference in 2 methods.

Electrochemical preparation of nano/micron structure transition metal-based catalysts for the oxygen evolution reaction.

Electrochemical water splitting is a promising technology for hydrogen production and sustainable energy conversion, but the existing electrolytic cells lack a sufficient number of robust and highly active anodic electrodes for the oxygen evolution reaction (OER). Electrochemical synthesis technology provides a feasible route for the preparation of independent OER electrodes with high utilization of active sites, fast mass transfer, and a simple preparation process. A comprehensive review of the electrochemical synthesis of nano/microstructure transition metal-based OER materials is provided. First, some fundamentals of electrochemical synthesis are introduced, including electrochemical synthesis strategies, electrochemical synthesis substrates, the electrolyte used in electrochemical synthesis, and the combination of electrochemical synthesis and other synthesis methods. Second, the morphology and properties of electrochemical synthetic materials are summarized and introduced from the viewpoint of structural design. Then, the latest progress regarding the development of transition metal-based OER electrocatalysts is reviewed, including the classification of metals/alloys, oxides, hydroxides, sulfides, phosphides, selenides, and other transition metal compounds. In addition, the oxygen evolution mechanism and rate-determining steps of transition metal-based catalysts are also discussed. Finally, the advantages, challenges, and opportunities regarding the application of electrochemical techniques in the synthesis of transition metal-based OER electrocatalysts are summarized. This review can provide inspiration for researchers and promote the development of water splitting technology.

Low-intensity extracorporeal shock wave therapy promotes recovery of sciatic nerve injury and the role of mechanical sensitive YAP/TAZ signaling pathway for nerve regeneration.

BACKGROUND: Histological and functional recovery after peripheral nerve injury (PNI) is of significant clinical value as delayed surgical repair and longer distances to innervate terminal organs may account for poor outcomes. Low-intensity extracorporeal shock wave therapy (LiESWT) has already been proven to be beneficial for injured tissue recovery on various pathological conditions. The objective of this study was to explore the potential effect and mechanism of LiESWT on PNI recovery. METHODS: In this project, we explored LiESWT's role using an animal model of sciatic nerve injury (SNI). Shockwave was delivered to the region of the SNI site with a special probe at 3 Hz, 500 shocks each time, and 3 times a week for 3 weeks. Rat Schwann cells (SCs) and rat perineurial fibroblasts (PNFs) cells, the two main compositional cell types in peripheral nerve tissue, were cultured in vitro, and LiESWT was applied through the cultured dish to the adherent cells. Tissues and cell cultures were harvested at corresponding time points for a reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence staining. Multiple groups were compared by using one-way analysis of variance followed by the Tukey-Kramer test for post hoc comparisons. RESULTS: LiESWT treatment promoted the functional recovery of lower extremities with SNI. More nerve fibers and myelin sheath were found after LiESWT treatment associated with local upregulation of mechanical sensitive yes-associated protein (YAP)/transcriptional co-activator with a PDZ-binding domain (TAZ) signaling pathway. In vitro results showed that SCs were more sensitive to LiESWT than PNFs. LiESWT promoted SCs activation with more expression of p75 (a SCs dedifferentiation marker) and Ki67 (a SCs proliferation marker). The SCs activation process was dependent on the intact YAP/TAZ signaling pathway as knockdown of TAZ by TAZ small interfering RNA significantly attenuated this process. CONCLUSION: The LiESWT mechanical signal perception and YAP/TAZ upregulation in SCs might be one of the underlying mechanisms for SCs activation and injured nerve axon regeneration.

Local continuous glial cell derived neurotrophic factor release using osmotic pump promotes parasympathetic nerve rehabilitation in an animal model of cavernous nerve injury induced erectile dysfunction.

BACKGROUND: Nerve injury-related erectile dysfunction (ED) is one of the types that respond poorly to conventional ED treatments. Our previous experiments have demonstrated the paracrine of various neurotrophic factors (NTFs) by stem cells or other treatment modalities as a potential mechanism in the recovery of nerve injury-related ED. Glial cell derived neurotrophic factor (GDNF) is one of the essential NTFs for the regeneration of nerve fibers, especially for parasympathetic nerves. The aim of this study is to explore if local continuous GDNF administration is beneficial for the functional and histological recovery of nerve injury induced ED. METHODS: Eight-week-old male Sprague-Dawley rats were used for this study. Rats were randomly grouped into 5: Sham surgery (Sham), bilateral cavernous nerve injury (BCNI) and placebo treatment, BCNI and 0.1 µg/100 µL GDNF treatment (BCNI+GDNF 0.1), BCNI and 1 µg/100 µL GDNF treatment (BCNI+GDNF 1), BCNI and 10 µg/100 µL GDNF treatment (BCNI+GDNF 10). GDNF was administered using an osmotic pump technique which would deliver GDNF locally and continuously for 28 days without the need for external connections or frequent handling of animals. Recovery of sexual function, nerve fibers regeneration, and expression of neurotrophic receptors were examined and compared among groups after the treatment. RESULTS: Local continuous GDNF release treatment increased the average number of intromissions in the sexual behavior test and intracavernous pressure (ICP) in the erectile function test in a dose dependent manner. Osmotic pump implantation induced increased local GDNF concentration and mild inflammatory response. Gene expression of GDNF receptors in major pelvic ganglion (MPG) and nerve regeneration along the urethra were partially promoted by GDNF. These changes were associated with increased nerve fibers especially the parasympathetic nerve fibers in dorsal nerve of penis (DNP) in GDNF treated groups. CONCLUSIONS: In conclusion, our project illustrated the promising effects of local continuous GDNF administration for the functional and histological recovery of nerve injury-induced ED.

Comparative study of intracavernous pressure and cavernous pathology after bilateral cavernous nerve crushing and resection in rats.

This study aimed to compare the effects of bilateral cavernous nerve crushing (BCNC) and bilateral cavernous nerve resection (BCNR) on intracavernous pressure (ICP) and cavernous pathology in rats and to explore the optimal treatment time for the BCNC and BCNR models. Seventy-two male rats aged 12 weeks were randomly divided into three equal groups: Sham (both cavernous nerves exposed only), BCNC (BCN crushed for 2 min), and BCNR (5 mm of BCN resected). Erectile function was then measured at 1 week, 3 weeks, and 5 weeks after nerve injury, and penile tissues were harvested for histological and molecular analyses by immunohistochemistry, immunofluorescence, Western blot, and cytokine array. We found that erectile function parameters including the maximum, area, and slope of ICP/mean arterial pressure (MAP) significantly decreased after BCNR and BCNC at 1 week and 3 weeks. At 5 weeks, no significant differences were observed in ICP/MAP between the BCNC and Sham groups, whereas the ICP/MAP of the BCNR group remained significantly lower than that of the Sham group. After BCNC and BCNR, the amount of neuronal-nitric oxide synthase-positive fibers, smooth muscle cells, and endothelial cells decreased, whereas the amount of collagen III content increased. These pathological changes recovered over time, especially in the BCNC group. Our findings demonstrate that BCNC leads to acute and reversible erectile dysfunction, thus treatment time should be restricted to the first 3 weeks post-BCNC. In contrast, the self-healing ability of the BCNR model is poor, making it more suitable for long-term treatment research.

Efficacy of dapoxetine treatment in Chinese patients with premature ejaculation and possible factors affecting efficacy in the real-world practice.

BACKGROUND: The treatment effect of dapoxetine in real-world practice is not well established. This study was to investigate the factors influencing efficacy of dapoxetine for the treatment of Premature ejaculation (PE) in the real-world setting. METHODS: Altogether 154 patients were followed up between Jan 2015 and Dec 2015. The clinical global impression of change (CGIC), premature ejaculation profile (PEP), the estimated intravaginal ejaculation latency time (eIELT) and estimated number of intravaginal thrusts before ejaculation (NITBE) were collected. The clinical characteristics of patients with CGIC = 0 and CGIC≥1 were compared. RESULTS: After 4 weeks treatment, an obvious improvement compared with the baseline was found regarding mean eIELT (2.4 ± 1.6 min vs 1.0 ± 0.7 min, P < 0.001) and mean NITBE (85.9 ± 61.9 times vs 37.4 ± 28.6 times, P < 0.001). The proportion of patients with a self-evaluation of at least "slightly better" and were categorized into "CGIC≥1" group was 70.1%. There were significant differences between patients in the "CGIC = 0" and "CGIC≥1" groups regarding mean NITBE (P = 0.010) and PEDT (P = 0.009) score at baseline. The adverse effects were acceptable. CONCLUSION: Dapoxetine was well-tolerated and improved the sexual satisfaction of patients with PE. The severity of PE based on PEDT and NITBE suggest that there could be an effectiveness change with dapoxetine use in real-world practice.

[CEP55 may be a potential therapeutic target for non-obstructive azoospermia with maturation arrest].

OBJECTIVE: To explore the effect of small interfering RNA (siRNA)-mediated CEP55 gene silencing on the proliferation of mouse spermatogonia. METHODS: Six patients with azoospermia diagnosed to have maturation arrest (3 cases) or normal spermatogenesis (3 cases) based on testicular biopsy between January 1 and December 31, 2017 in our center were examined for differential proteins in the testicular tissue using isobaric tags for relative and absolute quantitation (iTRAQ), and CEP55 was found to differentially expressed between the two groups of patients. We constructed a CEP55 siRNA for transfection in mouse spermatogonia and examined the inhibitory effects on CEP55 expressions using Western blotting and qPCR. The effect of CEP55 gene silencing on the proliferation of mouse spermatogonia was evaluated with CCK8 assay. RESULTS: In the testicular tissues from the 6 patients with azoospermia, iTRAQ combined with LC/MS/MS analysis identified over two hundred differentially expressed proteins, among which CEP55 showed the most significant differential expression between the patients with maturation arrest and those with normal spermatogenesis. The cell transfection experiment showed that compared with the cells transfected with the vehicle or the negative control sequence, the mouse spermatogonia transfected with CEP55 siRNA showed significantly lowered expressions of CEP55 mRNA and protein (P < 0.05) and significantly decreased proliferation rate as shown by CCK8 assay (P < 0.05). CONCLUSIONS: CEP55 may play a key role in spermatogenesis and may serve as a potential therapeutic target for non-obstructive azoospermia with maturation arrest.

The effects of microenergy acoustic pulses on an animal model of obesity-associated stress urinary incontinence. Part 1: Functional and histologic studies.

AIM: Obesity is a strong independent risk factor for urinary incontinence. Effective therapeutic approaches for obesity-associated stress urinary incontinence (OA-SUI) are lacking as the mechanisms remain unclear. The aim of our study is to explore the impacts of microenergy acoustic pulse (MAP) therapy on urethral and pelvic floor muscle structure and function in female lean and fatty rats. METHODS: A total 24 Zucker fatty (ZF) and 24 Zucker lean (ZL) female 24-week-old rats were grouped into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. For MAP treatment, 500 pulses were delivered at an energy level of 0.033 mJ/mm 2 and a frequency of 3 Hz and were applied twice a week for 4 weeks. After a 1-week washout, all rats underwent conscious cystometry and leak-point pressure (LPP) measurements followed by ex vivo organ-bath assay and histological study. RESULTS: ZF rats had lower LPP as compared to ZL rats, and MAP treatment significantly improved LPP in ZF rats (P < .05). Impaired muscle contractile activity (MCA) in organ-bath study was noted in ZF rats. MAP treatment significantly increased MCA in ZF rats (P < .05) and also increased the thickness of the striated muscle layer and the number of neuromuscular junctions (NMJs). In situ, MAP activated muscle satellite cells significantly (P < .05). CONCLUSIONS: Obesity impairs the function of both the urethral sphincter and the pelvic floor and leads to atrophy and distortion of the striated muscle in obese female rats. These issues contribute to OA-SUI. MAP improves continence by stimulating muscle regeneration and nerve innervation as well as by activating satellite cells.

Efficacy and safety of novel low-intensity pulsed ultrasound (LIPUS) in treating mild to moderate erectile dysfunction: a multicenter, randomized, double-blind, sham-controlled clinical study.

BACKGROUND: In our previous study, a novel low-intensity pulsed ultrasound (LIPUS) therapeutic device has been shown to improve erectile function non-invasively in a diabetic-induced erectile dysfunction (ED) animal model. METHODS: In order to investigate the efficacy and safety of LIPUS in the clinical treatment of patients with ED, a multicenter, randomized, double-blind, sham-treated, controlled clinical study was conducted at five medical centers, and 120 patients with mild to moderate ED were enrolled in the study. Patients were randomized into a sham-treated control group (40 patients) or a LIPUS-treated group (80 patients). LIPUS or sham treatment was applied to both sides of the penis shaft and crus for 5 min in each area, twice a week for four weeks. Assessment of efficacy and safety were evaluated using IIEF-5, Sexual Encounter Profile (SEP)-questionnaires 2/3, Global Assessment Question (GAQ), Erectile Hardness Score (EHS), Erection Quality Scale (EQS) score, and pain assessment [Visual Analogue Scale/Score (VAS)]. RESULTS: Ten patients in LIPUS treatment group and 6 patients in sham treatment control group were excluded and the dropout rate is 13.33%. Response to treatment was identified as IIEF-5 score increased more than 2/3/4 points of post-treatment (12W) compared to pre-treatment (0W). The response rate in treatment group was 54/80 (67.50%), which was significantly higher than control group 8/40 (20.00%) at 12 weeks (FAS analysis). The percentage of patients with positive answers to SEP-3 (successful vaginal intercourse) were 58.97%, 64.1%, and 73.08% 4, 8, and 12 weeks after treatment which were significantly higher than 28.95%, 31.58%, and 28.95% respectively in control group (FAS, P<0.05). The positive responsive rates for GAQ in treatment group were about 2 to 3 times of that in control group (P<0.05). No treatment-related adverse events (AEs) were found, including local petechia or ecchymosis and hematuria. CONCLUSIONS: Current study indicates that LIPUS can safely and effectively treat patients with mild to moderate ED without significant AEs, which is related to the mechanical force of LIPUS and can restore the pathological changes of the corpus cavernosum. LIPUS is a promising alternative treatment for ED treatment in the near future, while further research is remanded.

Treatment with low-energy shock wave alleviates pain in an animal model of uroplakin 3A-induced autoimmune interstitial cystitis/painful bladder syndrome.

Purpose: To investigate whether treatment with low-energy shock wave (LESW) alleviates pain and bladder dysfunction in a mouse model of uroplakin 3A (UPK3A)-induced interstitial cystitis/painful bladder syndrome (IC/PBS). Materials and Methods: Forty female BALB/c mice were divided into four groups (n=10/group): Sham, Sham+LESW, UPK3A, and UPK3A+LESW. At 6 weeks of age, mice were injected with an emulsion containing water and complete Freund's adjuvant with (UPK3A and UPK3A+LESW groups) or without (Sham and Sham+LESW groups) 200 µg of UPK3A. At 10 weeks, mice received a second dose of Freund's adjuvant to booster immunization. At 12 weeks, mice underwent pain assessment and a frequency volume chart (FVC) test as the pretreatment assessment. LESW treatment and pain assessment were conducted from 13 to 15 weeks. One week after the final treatment, pain assessment and the FVC were conducted again as the post-treatment assessment. Mice were euthanized and sacrificed at 17 weeks. Results: The presence of tactile allodynia and bladder dysfunction was significant in the UPK3A-injected mice. LESW raised the pain threshold and improved bladder function with decreased urinary frequency and increased mean urine output. Expression and secretion of local and systemic inflammatory markers, including tumor necrosis factor-α (TNF-α) and nerve growth factor (NGF), increased after UPK3A immunization. These markers were significantly decreased after LESW treatment (p<0.05). Conclusions: LESW treatment attenuated pain and bladder dysfunction in a UPK3A-induced model of IC/PBS. Local and systemic inflammation was partially controlled, with a reduced number of infiltrated inflammatory cells and reduced levels of TNF-α and NGF.

[Causes of oocyte vitrification and its value in assisted reproductive technology].

OBJECTIVE: To explore the causes of oocyte vitrification and its application in assisted reproduction. METHODS: We retrospectively analyzed the data of 26 patients with 27 cycles of oocyte vitrification cryopreservation undergoing intracytoplasmic sperm injection (ICSI) and embryo transfer between January, 2008 and October, 2018. The causes of oocyte vitrification and the outcomes of ICSI and clinical pregnancy were analyzed. RESULTS: The causes of oocytes vitrification included mainly azoospermia or severe spermatogenesis disorder of the husband, failure to obtain sperms from the husband, failure of the husband to be present on the day of oocyte retrieval and acute diseases of the husband to not allow sperm collection. A total of 274 oocytes were frozen in 27 oocyte retrieval cycles, and 217 eggs were thawed in 19 cycles with a survival rate of 81.11% (176/217). The normal fertilization rate, cleavage rate and high-quality embryo rate was 74.81% (98/131), 89.80% (88/98) and 36.73% (36/98), respectively. Fifteen patients underwent embryo transfer, and the clinical pregnancy rate and live birth rate was 53.33% (8/15) and 33.33% (5/15), respectively. Compared with patients below 35 years of age, the patients aged above 35 years had significantly lower oocyte survival rate after thawing (82.76% vs 74.42%, P=0.211), clinical pregnancy rate (77.78% vs 16.67%, P=0.041) and live birth rate (55.56% vs 0, P=0.044). CONCLUSIONS: Oocytes vitrification can be used as a remedy for infertile couples who fail to provide sperms due to male factors on the day of oocyte retrieval. Vitrification of the oocytes does not significantly affect the fertilization rate or the clinical pregnancy rate. The survival rate of the thawed oocytes is related to the age of the wife, and an age younger than 35 years can be optimal for achieving favorable clinical pregnancy outcomes after oocyte vitrification.

Low Intensity Pulsed Ultrasound Influences the Myogenic Differentiation of Muscle Satellite Cells in a Stress Urinary Incontinence Rat Model.

OBJECTIVE: To investigate the therapeutic effect of low intensity pulsed ultrasound (LIPUS) in a stress urinary incontinence (SUI) rat model and its influence on myogenic satellite cells. METHODS: Fifty Sprague-Dawley rats underwent vaginal distension and bilateral ovariectomy mimicking partum injury and menopause to construct SUI models, which were further randomized into 100 mW/cm2 LIPUS, 200 mW/cm2 LIPUS, 300 mW/cm2 LIPUS, and none-treatment control subgroups with 10 rats per subgroup. Ten rats served as mock operation control. Leak point pressure and bladder capacity were recorded 1 week after LIPUS treatment. Immunofluorescence staining and Western blot were performed to examine histological changes, myodifferentiation, and signaling pathway. RESULTS: Here,we found the leak point pressure and bladder capacity were restored in 200 mW/cm2 LIPUS and 300 mW/cm2 LIPUS groups, but not in 100 mW/cm2 LIPUS group. More robust striated muscle regeneration was observed in 200 mW/cm2 LIPUS group comparing with the SUI none-treatment group. Moreover, we found LIPUS activated the myodifferentiation of muscle satellite cells, which is correlated to p38 phosphorylation level. CONCLUSION: LIPUS restored the leak point pressure and bladder capacity, and activated satellite cell myodifferentiation in SUI rat model.

Icariside II ameliorates endothelial dysfunction by regulating the MAPK pathway via miR-126/SPRED1 in diabetic human cavernous endothelial cells.

AIM: The aim of the study was to investigate whether miR-126, a regulator of MAPK signaling via targeting sprouty-related EVH1 domain-containing protein 1 (SPRED1) mRNA, is involved in the process by which icariside II (ICA II) ameliorates endothelial dysfunction in human cavernous endothelial cells (hCECs) exposed to a diabetic-like environment. MATERIALS AND METHODS: Primary hCECs were isolated and divided into three groups, normal control, diabetes mellitus (DM), and DM treated with ICA II. The cell proliferation and migration abilities of the hCECs were examined. The expression levels of endothelial-related microRNAs and relative target mRNAs (SPRED1, phosphoinositol-3 kinase regulatory subunit 2, and vascular cell adhesion molecule 1) of miR-126 were determined by real-time PCR. The protein expression of endothelial nitric oxide synthase, receptor for advanced glycation end products, and SPRED1, and MAPK signaling activities was determined by Western blot analysis. In addition, miR-126 agomir and antagomir were used for transfection into hCECs to further testify the association between miR-126 and its targeting mRNA SPRED1. RESULTS: hCECs induced with glucose plus advanced glycation end product-BSA showed a significant decrease in endothelial nitric oxide synthase, Ki-67, and miR-126 expression; a downregulated cell migration ability and an increased receptor for advanced glycation end products level. ICA II could partially reverse these changes. SPRED1 mRNA showed a contrary tendency with the miR-126-3p changes. The level of SPRED1 protein increased after the hCECs were induced with glucose plus advanced glycation end product-BSA, and ICA II could rescue its aberrant expression. In addition, the MAPK pathway was downregulated in the hCECs under diabetic conditions, and ICA II could partially enhance its signaling activities. miR-126 was obviously downregulated, and SPRED1 was accordingly upregulated after miR-126 antagomir transfection, while ICA II treatment could recover the expressions of both miR-126 and SPRED1. Moreover, the upregulation of miR-126 and the inhibition of SPRED1 were noticed in the diabetic hCECs by further transfection with miR-126 agomir. CONCLUSION: ICA II could ameliorate endothelial dysfunction by regulating the MAPK pathway via miR-126/SPRED1 in hCECs exposed to a diabetic-like environment, and ICA II might be a protective agent for endothelial function in diabetic ED.

Transgenic animal model for studying the mechanism of obesity-associated stress urinary incontinence.

OBJECTIVE: To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity-associated stress urinary incontinence (SUI). MATERIALS AND METHODS: Two study arms were created: a ZL arm including 16-week-old female ZL rats (ZUC-Leprfa 186; n = 12) and a ZF arm including 16-week-old female ZF rats (ZUC-Leprfa 185; n = 12). I.p. insulin tolerance testing was carried out before functional study. Metabolic cages, conscious cystometry and leak point pressure (LPP) assessments were conducted. Urethral tissues were harvested for immunofluorescence staining to check intramyocellular lipid (IMCL) and sphincter muscle (smooth muscle and striated muscle) composition. RESULTS: The ZF rats had insulin resistance, a greater voiding frequency and lower LPP compared with ZL rats (P < 0.05), with more IMCL deposition localized in the urethral striated muscle fibres of the ZF rats (P < 0.05). The thickness of the striated muscle layer and the ratio of striated muscle to smooth muscle were lower in ZF than in ZL rats. CONCLUSION: Obesity impairs urethral sphincter function via IMCL deposition and leads to atrophy and distortion of urethral striated muscle. The ZF rats could be a consistent and reliable animal model in which to study obesity-associated SUI.

Comparison of Topical Hemostatic Agents in a Swine Model of Extremity Arterial Hemorrhage: BloodSTOP iX Battle Matrix vs. QuikClot Combat Gauze.

BloodSTOP iX Battle Matrix (BM) and QuikClot Combat Gauze (CG) have both been used to treat traumatic bleeding. The purpose of this study was to examine the efficacy and initial safety of both products in a swine extremity arterial hemorrhage model, which mimics combat injury. Swine (37.13 ± 0.56 kg, NBM = 11, NCG = 9) were anesthetized and splenectomized. We then isolated the femoral arteries and performed a 6 mm arteriotomy. After 45 s of free bleeding, either BM or CG was applied. Fluid resuscitation was provided to maintain a mean arterial pressure of 65 mmHg. Animals were observed for three hours or until death. Fluoroscopic angiography and wound stability challenge tests were performed on survivors. Tissue samples were collected for histologic examination. Stable hemostasis was achieved in 11/11 BM and 5/9 CG subjects, with recovery of mean arterial pressure and animal survival for three hours (p < 0.05, Odds Ratio (OR) = 18.82 (0.85-415.3)). Time to stable hemostasis was shorter for the BM-treated group (4.8 ± 2.5 min vs. 58 ± 20.1 min; Median = 2, Interquartile Range (IQR) = 0 min vs. Median = 60, IQR = 120 min; p < 0.05) and experienced longer total stable hemostasis (175.2 ± 2.5 min vs. 92.4 ± 29.9 min; Median = 178, IQR = 0 min vs. Median = 120, IQR = 178 min; p < 0.05). Post-treatment blood loss was lower with BM (9.5 ± 2.4 mL/kg, Median = 10.52, IQR = 13.63 mL/kg) compared to CG (29.9 ± 9.9 mL/kg, Median = 29.38, IQR = 62.44 mL/kg) (p = 0.2875). Standard BM products weighed less compared to CG (6.9 ± 0.03 g vs. 20.2 ± 0.4 g) (p < 0.05) and absorbed less blood (3.4 ± 0.8 g vs. 41.9 ± 12.3 g) (p < 0.05). Fluoroscopic angiography showed recanalization in 5/11 (BM) and 0/5 (CG) surviving animals (p = 0.07, OR = 9.3 (0.41-208.8)). The wound stability challenge test resulted in wound re-bleeding in 1/11 (BM) and 5/5 (CG) surviving animals (p < 0.05, OR = 0.013 (0.00045-0.375)). Histologic evidence indicated no wound site, distal limb or major organ damage in either group. BM is more effective and portable in treating arterial hemorrhage compared to CG. There was no histologic evidence of further damage in either group.

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model.

INTRODUCTION: Erectile dysfunction (ED) caused by pelvic injuries is a common complication of civil and battlefield trauma with multiple neurovascular factors involved, and no effective therapeutic approach is available. AIMS: To test the effect and mechanisms of low-energy shock wave (LESW) therapy in a rat ED model induced by pelvic neurovascular injuries. METHODS: Thirty-two male Sprague-Dawley rats injected with 5-ethynyl-2'-deoxyuridine (EdU) at newborn were divided into 4 groups: sham surgery (Sham), pelvic neurovascular injury by bilateral cavernous nerve injury and internal pudendal bundle injury (PVNI), PVNI treated with LESW at low energy (Low), and PVNI treated with LESW at high energy (High). After LESW treatment, rats underwent erectile function measurement and the tissues were harvested for histologic and molecular study. To examine the effect of LESW on Schwann cells, in vitro studies were conducted. MAIN OUTCOME MEASUREMENTS: The intracavernous pressure (ICP) measurement, histological examination, and Western blot (WB) were conducted. Cell cycle, Schwann cell activation-related markers were examined in in vitro experiments. RESULTS: LESW treatment improves erectile function in a rat model of pelvic neurovascular injury by leading to angiogenesis, tissue restoration, and nerve generation with more endogenous EdU(+) progenitor cells recruited to the damaged area and activation of Schwann cells. LESW facilitates more complete re-innervation of penile tissue with regeneration of neuronal nitric oxide synthase (nNOS)-positive nerves from the MPG to the penis. In vitro experiments demonstrated that LESW has a direct effect on Schwann cell proliferation. Schwann cell activation-related markers including p-Erk1/2 and p75 were upregulated after LESW treatment. CONCLUSION: LESW-induced endogenous progenitor cell recruitment and Schwann cell activation coincides with angiogenesis, tissue, and nerve generation in a rat model of pelvic neurovascular injuries.

Urethral musculature and innervation in the female rat.

AIMS: The urethral sphincter and urethral muscle innervation are critically involved in maintaining continence, especially in the female. However, the urethral muscle type and distribution, as well as the urethral nerves are far from being well documented. Our aim was to clearly identify the distribution of urethral striated muscle, smooth muscle, and urethral nerves. METHODS: In a cohort analysis of 3-month-old female Sprague-Dawley rats, cross and longitudinal sections of female rat urethra were extensively investigated using morphological techniques. Urethras were harvested to the sections, in order to provide both global and detailed visions of the urethra. H&E, Masson's Trichrome, phalloidin and immunoflourence stains were used. The cytoarchitecture, nitrergic, and cholinergic innervations were mainly investigated. Different layers of the segments of urethra were traced to draw curve graphs that represent the thickness of each muscle layer of urethral wall. RESULTS: The results showed that the primary peak of striated muscle is in the middle urethra. The inner layer close to mucosa was found to contain longitudinal smooth muscle. Near the bladder orifice, the circular smooth muscle dominates, which becomes thinner distally throughout the rest of urethra. In the middle urethra the vast majority of the urethral muscle are circularly oriented striated muscle cells. Typical nerve endings were present in high power images to show the different characteristic features of nerve innervation. CONCLUSIONS: This study has illustrated the detailed morphological structure and innervations of the normal female rat urethra and can serve as a basis for further study of stress urinary incontinence (SUI).

Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats.

PURPOSE: To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on reversing diabetic nephropathy in streptozotocin (STZ)-induced type I diabetic rats. METHODS: Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16), diabetes mellitus group (DM; n=16), and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16). Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day) for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-ß/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-ß/Smad/CTGF) signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues. RESULTS: Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-ß/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney. CONCLUSION: ICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-ß/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue.