HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway.

BACKGROUND: Heart failure (HF) is a heterogeneous syndrome that affects millions worldwide, resulting in substantial health and economic burdens. However, the molecular mechanism of HF pathogenesis remains unclear. METHODS: HF-related key genes were screened by a bioinformatics approach.The impacts of HAPLN1 knockdown on Angiotensin II (Ang II)-induced AC16 cells were assessed through a series of cell function experiments. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of oxidative stress and apoptosis-related factors. The HF rat model was induced by subcutaneous injection isoprenaline and histopathologic changes in the cardiac tissue were assessed by hematoxylin and eosin (HE) staining and echocardiographic index. Downstream pathways regulated by HAPLN1 was predicted through bioinformatics and then confirmed in vivo and in vitro by western blot. RESULTS: Six hub genes were screened, of which HAPLN1, FMOD, NPPB, NPPA, and COMP were overexpressed, whereas NPPC was downregulated in HF. Further research found that silencing HAPLN1 promoted cell viability and reduced apoptosis in Ang II-induced AC16 cells. HAPLN1 knockdown promoted left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), while decreasing left ventricular end-systolic volume (LVESV) in the HF rat model. HAPLN1 knockdown promoted the levels of GSH and suppressed the levels of MDA, LDH, TNF-α, and IL-6. Mechanistically, silencing HAPLN1 activated the PKA pathway, which were confirmed both in vivo and in vitro. CONCLUSION: HAPLN1 knockdown inhibited the progression of HF by activating the PKA pathway, which may provide novel perspectives on the management of HF.

Adaptive under-sampling strategy for fast imaging in compressive sensing-based atomic force microscopy.

Compressive sensing (CS) can reconstruct the rest information almost without distortion by advanced computational algorithm, which significantly simplifies the process of atomic force microscope (AFM) scanning with high imaging quality. In common CS-AFM, the partial measurements randomly come from the whole region to be measured, which easily leads to detail loss and poor image quality in regions of interest (ROIs). Consequently, important microscopic phenomena are missed probably. In this paper, we developed an adaptive under-sampling strategy for CS-AFM to optimize the process of sampling. Under a certain under-sampling ratio, the weight coefficient of ROIs and regions of base (ROBs) were set to control the distribution of under-sampling points and corresponding measurement matrix. A series of simulations were completed to demonstrate the relationship between the weight coefficient of ROIs and image quality. After that, we verified the effectiveness of the method on our homemade AFM. Through a lot of simulations and experiments, we demonstrated how the proposed method optimized the sampling process of CS-AFM, which speeded up the process of AFM imaging with high quality.

Piezo2 Channel Upregulation is Involved in Mechanical Allodynia in CYP-Induced Cystitis Rats.

Mechanical sensing Piezo2 channel in primary sensory neurons has been shown contribute to mechanical allodynia in somatic chronic pain conditions. Interstitial cystitis (IC)-associated pain is often triggered by bladder filling, a presentation that mimics the mechanical allodynia. In the present study, we aimed to examine the involvement of sensory Piezo2 channel in IC-associated mechanical allodynia using a commonly employed cyclophosphamide (CYP)-induced IC model rat. Piezo2 channels in dorsal root ganglia (DRGs) was knocked down by intrathecal injections of Piezo2 anti-sense oligodeoxynucleotides (ODNs) in CYP-induced cystitis rats, and mechanical stimulation-evoked referred bladder pain was measured in the lower abdomen overlying the bladder using von Frey filaments. Piezo2 expression at the mRNA, protein, and functional levels in DRG neurons innervating the bladder was detected by RNA-fluorescence in situ hybridization, western blotting, immunofluorescence, and Ca2+ imaging, respectively. We found that Piezo2 channels were expressed on most (> 90%) of the bladder primary afferents, including afferents that express CGRP, TRPV1 and stained with isolectin B4. CYP-induced cystitis was associated with Piezo2 upregulation in bladder afferent neurons at the mRNA, protein, and functional levels. Knockdown of Piezo2 expression in DRG neurons significantly suppressed mechanical stimulation-evoked referred bladder pain as well as bladder hyperactivity in CYP rats compared to CYP rats treated with mismatched ODNs. Our results suggest upregulation of Piezo2 channels is involved in the development of bladder mechanical allodynia and bladder hyperactivity in CYP-induced cystitis. Targeting Piezo2 might be an attractive therapeutic approach for IC-related bladder pain.

Equivalent Electromechanical Model for Quartz Tuning Fork Used in Atomic Force Microscopy.

Quartz tuning forks (QTFs) are self-sensing and possess a high quality factor, allowing them to be used as probes for atomic force microscopes (AFMs) for which they offer nano-scale resolution of sample images. Since recent work has revealed that utilizing higher-order modes of QTFs can offer better resolution of AFM images and more information on samples, it is necessary to understand the relationship between the vibration characteristics of the first two symmetric eigenmodes of quartz-based probes. In this paper, a model that combines the mechanical and electrical characteristics of the first two symmetric eigenmodes of a QTF is presented. Firstly, the relationships between the resonant frequency, amplitude, and quality factor between the first two symmetric eigenmodes are theoretically derived. Then, a finite element analysis is conducted to estimate the dynamic behaviors of the analyzed QTF. Finally, experimental tests are executed to verify the validity of the proposed model. The results indicate that the proposed model can accurately describe the dynamic properties of a QTF in the first two symmetric eigenmodes either under electrical or mechanical excitation, which will provide a reference for the description of the relationship between the electrical and mechanical responses of the QTF probe in the first two symmetric eigenmodes as well as the optimization of higher modal responses of the QTF sensor.

Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3ß/snail pathway.

BACKGROUND: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate cancer. METHODS: The expression of DANCR, microRNA (miR)-185-5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate cancer tissues and normal tissues, five prostate cancer cell lines and one epithelial cell line was assessed by a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4-2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial-mesenchymal transition (EMT) protein expression were tested via cell counting kit-8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR-185-5p and LASP1 were verified by a dual-luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4-2 cells. The involvement of the signaling pathway was examined using a p-FAK inhibitor. RESULTS: DANCR and LASP1 expression was enhanced, whereas miR-185-5p expression was diminished in prostate cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1-S transition and expression of EMT proteins of the transfected PC3 and C4-2 cells. DANCR sponged miR-185-5p to upregulate LASP1 expression. DANCR-miR-185-5p-LASP1 axis activates the FAK/PI3K/AKT/GSK3ß/Snail pathway to promote the malignant properties of PC3 and C4-2 cells. CONCLUSIONS: These findings suggest that DANCR exerts oncogenic roles in prostate cancer via the miR-185-5p/LASP1 axis activating the FAK/PI3K/AKT/GSK3ß/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate cancer.

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.

Systematically transplanted human gingiva-derived mesenchymal stem cells regulate lipid metabolism and inflammation in hyperlipidemic mice with periodontitis.

Gingiva-derived mesenchymal stem cells (GMSCs) have been the focus of extensive research due to their numerous distinct properties, including their homing to injury sites and their contribution to tissue regeneration. However, the role of transplanted GMSCs in the regulation of lipid metabolism and inflammation in hyperlipidemic mice with periodontitis has not been demonstrated. In the present study, apolipoprotein E-deficient (ApoE-/-) mice were used to establish a hyperlipidemia model with periodontitis and divided into two groups: Group B and Group C (n=20 per group), and wild-type C57BL/6J mice without any treatment were assigned to Group A (n=20). Animals in Group C were then injected with human GMSCs through the tail vein and animals in Group B were injected with α-MEM as control. Animals were sacrificed at indicated time points. Serum was collected to determine the lipids and inflammatory cytokines. Liver samples were collected to estimate lipid-associated gene expression. Morphometric and histological analyses were performed to maxillaries. The results demonstrated that the delivery of GMSCs led to a significant decrease in triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL), interleukin (IL)-6, tumor necrosis factor (TNF)-α, alveolar bone loss (ABL), and sterol regulatory element binding protein-1c (SREBP-1c) mRNA, and a significant increase in high density lipoprotein cholesterol (HDL), IL-10 and peroxisome proliferator-activated receptor α (PPARα) mRNA in Group C compared to Group B. Histological examination showed increased formation of new bone and higher alveolar bone height in Group C. Systematically transplanted GFP-positive cells were detected through both fluorescence microscope observation and immunohistochemical staining in the periodontal tissues. Overall, systematically transplanted GMSCs attenuated the hyperlipidemia and inflammatory responses in hyperlipidemic mice with periodontitis, and improved periodontal tissue regeneration.

Dendrite-free deposition on lithium anode toward long-life and high-stable Li//graphite dual-ion battery.

Metallic lithium protection plays a crucial role on improving the electrochemical properties of Li-anode-based batteries. Herein, for an advanced Li//graphite dual-ion battery, constructing a robust and conductive film of carbon nanofibers on a Li anode effectively achieves dendrite-free Li growth and hence significantly enhances the long-life cyclic stability.

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.

The treatment of systematically transplanted gingival mesenchymal stem cells in periodontitis in mice.

Cell-based tissue engineering is a promising alternative for periodontal regeneration as current therapies fail to reconstitute tissue damage caused by periodontitis. As newly identified postnatal stem cells, gingiva-derived mesenchymal stem cells (GMSCs) have been focused on for isolation and expansion in vitro of cells with multi-differentiation potential and immunomodulatory capacities. It has been demonstrated that systemically delivered GMSCs can home to the mandibular bone defect sites and promote bone regeneration. However, the role of transplanted GMSCs in the treatment of periodontitis has not been reported. In the present study, GMSCs were transplanted into C57BL/6J mice with periodontitis via the tail vein to investigate the contribution of GMSCs to periodontal tissue regeneration. Results demonstrated that the alveolar bone heights of mice with transplanted GMSCs were significantly increased compared with the control groups and GMSCs were detected in newly formed periodontal ligament and alveolar bone. The results of the present study implied that systemically transplanted GMSCs could home to periodontal injury sites and promote periodontal tissue regeneration.

An experimental hyperlipidemia model with periodontitis in mice.

PURPOSE: In many animal models and clinical trials, the relationship between periodontitis and hyperlipidemia is bidirectional and interlinked. In this study, an experimental hyperlipidemia model with periodontitis in mice is introduced. METHODS: C57BL/6J mice were assigned into group A and B and Apolipoprotein E-deficient (ApoE-/-) mice into group C. After 4 weeks of a high fat diet (HFD), group B and C were ligated on the maxillary second molar tooth, and mice were sacrificed after 8 weeks of the HFD. Levels of lipids, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α in serum after 0, 4, and 8 weeks were determined. Alveolar bone loss (ABL) was assessed under stereomicroscope. Maxillary bones and atherosclerotic lesion area in the aorta were collected for hematoxylin and eosin (HE) staining. RESULTS: After feeding with a HFD for 4 weeks, group C demonstrated dramatic increases in serum lipid levels. The ABL and levels of IL-6, IL-10, and TNF-α in group C was significantly higher than those of group A and B (P<0.05). Atherosclerotic lesions were observed in group C. CONCLUSIONS: These data demonstrate that an experimental hyperlipidemia model with periodontitis in mice is successfully established by ligation in ApoE-/- mice. This method is economical and time saving, and worthy of more general application.

Application of pulsed arterial resuscitation in a rabbit model of hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is characterized by tissue hypoperfusion caused by a sharp reduction in the effective circulating volume of blood. The key to successful resuscitation lies in eliminating the shock as soon as possible while simultaneously restoring blood perfusion to vital organs. We present the applicability of pulsed arterial blood reinfusion for resuscitation of hemorrhagic shock. METHODS: Sixty rabbits were randomly assigned to resuscitation and control groups. A rabbit hemorrhagic shock model was developed by bloodletting from the carotid artery. The dynamic changes in blood pressure, urine output, blood lactate, and other indicators were measured. RESULTS: Compared with the control group, the mean arterial pressure (MAP), pulse pressure, and urine output were significantly higher in the resuscitation group at 60 min (MAP: 83.67±3.90 vs. 38.19±3.50 mmHg, p<0.001; pulse difference: 16.46±2.21 vs. 10.27±2.99 mmHg, p<0.001; urine output: 3.68±0.74 vs. 0.10±0.05 mL·kg-1·min-1, p<0.001), whereas the serum lactate level was significantly lower (3.82±0.50 vs. 6.49±0.61 mmol/L, p<0.001). In addition, the resuscitation group had a significantly higher lactate clearance rate (30 min: 0.26%±0.11% vs. 0.25%±0.14%, p<0.001; 60 min: 0.30%±0.09% vs. 0.67%±0.26%, p<0.001) than the control group. CONCLUSION: Pulsed arterial resuscitation might be useful for emergency treatment of hemorrhagic shock.

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.

Signal transduction by M3 muscarinic acetylcholine receptor in prostate cancer.

The present study aimed to investigate the potential mechanisms used during signal transduction by M3 muscarinic acetylcholine receptor (CHRM3) in prostate cancer. The microarray datasets of GSE3325, including 5 clinically localized primary prostate cancers and 4 benign prostate tissues, were downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in primary prostate cancer tissues compared with benign controls were screened using the Limma package. Gene Ontology and pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. Next, a protein-protein interaction (PPI) network was constructed. Additionally, microRNAs (miRNAs) associated with DEGs were predicted and miRNA-target DEG analysis was performed using a Web-based Gene Set Analysis Toolkit. Finally, the PPI network and the miRNA-target DEG network were integrated using Cytoscape. In total, 224 DEGs were screened in the prostate cancer tissues, including 113 upregulated and 111 downregulated genes. CHRM3 and epidermal growth factor (EGF) were enriched in the regulation of the actin cytoskeleton. EGF and v-myc avian myelocytomatosis viral oncogene homolog (Myc) were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. EGF with the highest degree of connectivity was the hub node in the PPI network, and miR-34b could interact with Myc directly in the miRNA-target DEG network. EGF and Myc may exhibit significant roles in the progression of prostate cancer via regulation of the actin cytoskeleton and the MAPK signaling pathway. CHRM3 may activate these two pathways in prostate cancer progression. Thus, these two key factors and pathways may be crucial mechanisms during signal transduction by CHRM3 in prostate cancer.

[Clinical application of preoperative imaging evaluation in the anterolateral thigh flap transplantation: comparison of computed tomography angiography, digital subtract angiography and magnetic resonance angiography].

OBJECTIVE: To evaluate the value of three preoperative imaging methods in the anterolateral thigh flap (ALT) transplantation. METHODS: According to preoperative imaging, patients who underwent the ALT flap transplantation were divided into three groups: computed tomography angiography (CTA) group, digital subtract angiography ( DSA) group and magnetic resonance angiography (MRA) group. There were fifteen cases in each group. We compared the imaging quality of the ALT artery among these groups and recorded the parameters of lateral femoral circumflex artery, descending branches and perforators including type, course and size. The results from images were compared with intraoperative findings. The success rate and complications were also recorded. RESULTS: The preoperative imaging accuracy of the types of the lateral femoral circumflex artery and descending branch was more than 92.3%, with no significant different between any two of three groups (P > 0.05). The difference in diameters of descending branches and perforators from preoperative measurement and from intraoperative measurement was also not significant between any two of the three groups; the success rate and complications were not also obviously different (P > 0.05 , P > 0.05, respectively). CONCLUSIONS: Preoperative mapping using CTA, DSA and MRA is a feasible and reliable method for the flap design in ALT transplantation. As a preoperative evaluation means, CTA and MRA may replace DSA in the ALT transplantation.

Outcomes of Microscopic Subinguinal Varicocelectomy With and Without the Assistance of Doppler Ultrasound: A Randomized Clinical Trial.

OBJECTIVE: To compare the surgical outcomes and complications between microscopic subinguinal varicocelectomy (MV) and intraoperative vascular Doppler ultrasound-assisted microscopic subinguinal varicocelectomy (IVDU-MV) for infertile patients with varicoceles. MATERIALS AND METHODS: One hundred seventy-two infertile patients with varicoceles were randomly divided into IVDU-MV group (n = 85) and MV group (n = 87). We assessed patients' operative and postoperative parameters, semen parameters, and the pregnancy rate. The mean follow-up period was 21 months (range, 13-34 months). RESULTS: The operative time was significantly shorter in the IVDU-MV group than MV group (41.9 ± 13.6 vs 52.7 ± 14.1 minutes, P <.05). The number of intraoperative arteries spared was significantly greater in the IVDU-MV group than the MV group (1.9 ± 0.8 vs 1.3 ± 0.7, P <.05). In addition, the average number of spermatic veins ligated was significantly greater in the IVDU-MV group (7.8 ± 2.1 vs 7.0 ± 1.9, P <.05). Lymphatic spared showed no significant difference (P >.05). The postoperative hospital stay showed no significant difference. Sperm concentration, sperm motility, and the percentage of grade a+b sperm were significantly increased in both groups at 3, 6, and 12 months after surgery (P <.05), and the sperm motility was higher in IVDU-MV than MV group (43.98 ± 7.64 vs 36.98 ± 5.10, P <.05) in 12 months after surgery. Sperm morphology was comparable between the 2 groups. The pregnancy rate showed no significant difference (36.8% of the MV vs 34.1% of the IVDU-MV, P >.05). CONCLUSION: Our study demonstrated that both MV and IVDU-MV are effective methods for the improvement of semen parameters in infertile men with varicocele, with a natural conception rate of 35% over a mean follow-up of 21 months. Compared with MV, IVDU-MV is superior in shortening operative time, increasing the number of spermatic arteries spared, spermatic veins ligated, and sperm motility after surgery. IVDU should be routinely used as an effective tool to improve outcomes and safety of varicocelectomy.

Regulation Roles of MICA and NKG2D in Human Renal Cancer Cells.

OBJECTIVE: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. MATERIALS AND METHODS: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. RESULTS: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies (P<0.05), and serum containing sMICA can obviously lower the function of NKG2D (P<0.05). CONCLUSIONS: The interaction of mMICA and NKG2D play important roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA may mediate tumor immune escape through down- regulated NKG2D expression.

EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells.

BIX-01294, an euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor, has been reported to induce apoptosis in human neuroblastoma cells and inhibit the proliferation of bladder cancer cells. However, the definite mechanism of the apoptosis mediated by BIX-01294 in bladder cancer cells remains unclear. In the present study, we found that BIX-01294 induced caspase-dependent apoptosis in human bladder cancer cells. Moreover, our data show BIX-01294 stimulates endoplasmic reticulum stress (ER stress) and up-regulated expression of PMAIP1 through DDIT3 up-regulation. Furthermore, down-regulation of the deubiquitinase USP9X by BIX-01294 results in downstream reduction of MCL1 expression, leading to apoptosis eventually. Thus, our findings demonstrate PMAIP1-USP9X-MCL1 axis may contribute to BIX-01294-induced apoptosis in human bladder cancer cells.