[Effect of Tetrastigma hemsleyanum on sepsis and mechanism based on network pharmacology and experimental verification].

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1ß, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1ß, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lß, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.

Stable and Efficient Nanofilm Pure Evaporation on Nanopillar Surfaces.

Molecular dynamics simulations were conducted to systematically investigate how to maintain and enhance nanofilm pure evaporation on nanopillar surfaces. First, the dynamics of the evaporation meniscus and the onset and evolution of nanobubbles on nanopillar surfaces were characterized. The meniscus can be pinned at the top surface of the nanopillars during evaporation for perfectly wetting fluid. The curvature of the meniscus close to nanopillars varies dramatically. Nanobubbles do not originate from the solid surface, where there is an ultrathin nonevaporation film due to strong solid-fluid interaction, but originate and evolve from the corner of nanopillars, where there is a quick increase in potential energy of the fluid. Second, according to a parametric study, the smaller pitch between nanopillars (P) and larger diameter of nanopillars (D) are found to enhance evaporation but also raise the possibility of boiling, whereas the smaller height of nanopillars (H) is found to enhance evaporation and suppress boiling. Finally, it is revealed that the nanofilm thickness should be maintained beyond a threshold, which is 20 Å in this work, to avoid the suppression effect of disjoining pressure on evaporation. Moreover, it is revealed that whether the evaporative heat transfer is enhanced on the nanopillar surface compared with the smooth surface is also affected by the nanofilm thickness. The value of nanofilm thickness should be determined by the competition between the suppression effect on evaporation due to the decrease in the volume of supplied fluid and the existence of capillary pressure and the enhancement effect on evaporation due to the increase in the heating area. Our work serves as the guidelines to achieve stable and efficient nanofilm pure evaporative heat transfer on nanopillar surfaces.

Extracellularly oxidative activation and inactivation of matured prodrug for cryptic self-resistance in naphthyridinomycin biosynthesis.

Understanding how antibiotic-producing bacteria deal with highly reactive chemicals will ultimately guide therapeutic strategies to combat the increasing clinical resistance crisis. Here, we uncovered a distinctive self-defense strategy featured by a secreted oxidoreductase NapU to perform extracellularly oxidative activation and conditionally overoxidative inactivation of a matured prodrug in naphthyridinomycin (NDM) biosynthesis from Streptomyces lusitanus NRRL 8034. It was suggested that formation of NDM first involves a nonribosomal peptide synthetase assembly line to generate a prodrug. After exclusion and prodrug maturation, we identified a pharmacophore-inactivated intermediate, which required reactivation by NapU via oxidative C-H bond functionalization extracellularly to afford NDM. Beyond that, NapU could further oxidatively inactivate the NDM pharmacophore to avoid self-cytotoxicity if they coexist longer than necessary. This discovery represents an amalgamation of sophisticatedly temporal and spatial shielding mode conferring self-resistance in antibiotic biosynthesis from Gram-positive bacteria.

Treatment of primary cardiac angiosarcoma in a 35 weeks pregnant woman.

BACKGROUND: Cardiac angiosarcoma is a rare but highly malignant cardiac tumor. It is characterized by poor prognosis, and current treatment approaches are not effective. CASE PRESENTATION: A 37-year-old female with 35 weeks pregnancy experienced chest tightness and shortness of breath for 1 month. She was diagnosed with primary cardiac angiosarcoma. Delivery of fetus was performed early to treat the mother. The patient underwent resection of the tumor then she was treated with chemotherapy. However, the tumor recurred 11 months after surgery. CONCLUSION: Angiosarcoma is a highly malignant tumor explaining recurrence of the tumor recurred after surgery. Cardiac angiosarcoma should be treated through a comprehensive treatment plan, comprising surgery, radiotherapy, and chemotherapy approaches.

[The Clinical Effectiveness of Neural Network-based Boundary Recognition of Upper Abdominal Organs on CT Images].

OBJECTIVE: To assess the clinical effectiveness of boundary recognition of upper abdomen organs on CT images based on neural network model and the combination of different slices. METHODS: A total of 2 000 patients who underwent upper abdomen enhanced CT scans from March 2018 to March 2019 were included in the study. The quality of the CT images met the requirements for clinical diagnosis. Eight boundary layers (the upper and lower edge of liver, the upper and lower edge of spleen, the lower edge of left kidney, the lower edge of right kidney, the lower edge of the stomach and the lower edge of the gallbladder) of the main organs in the upper abdomen were labeled. The model training (training set, verification set and test set) based on different neural network methods and combinations of different slices were then performed to assess the accuracy of boundary recognition. Furthermore, clinical data from 50 cases were used as test group for assessing the accuracy and clinical effectiveness of this model. RESULTS: The fusion model created by integrating the two models according to different weight ratios yielded the highest accuracy, and then followed the EfficientNet-b3 model, with the Xception model showing the lowest accuracy. In each model, the boundary recognition accuracy of 5-slice image is higher than that of 3-silce image, and that of 1-slice image is the lowest. The recognition accuracy of fusion model of the 5-continuous-slice image for upper edge of liver, lower edge of liver, upper edge of spleen, lower edge of spleen, lower edge of left kidney, lower edge of right kidney, lower edge of stomach and lower edge of gallbladder was 91%, 87%, 92%, 85%, 92%, 95%, 76% and 74%, respectively. The fusion model was checked with the effectiveness data of 50 cases, yielding 88%, 86%, 88%, 80%, 82%, 80%, 69%, and 65% accuracy for 8-slice image, respectively, and the accuracy of meeting clinical application requirement was as high as 98%, 98%, 95%, 98%, 99%, 98%, 80% and 77%, respectively. CONCLUSION: By increasing boundary change logics in the continuous slices, the fusion model integrating different weight proportions demonstrates the highest accuracy for identifying the boundary of upper abdominal organs on CT images, achieving high examination effectiveness in clinical practice.

Generation and Evolution of Nanobubbles on Heated Nanoparticles: A Molecular Dynamics Study.

Molecular dynamics simulations were conducted to investigate the generation and evolution of nanobubbles on heated gold-like nanoparticles (GNPs). The effects of surface wettability (ß) and heating intensity (Q) of the GNPs are studied. We found that nanobubbles are generated faster on the superhydrophobic GNP than on the superhydrophilic GNP where nanobubble formation appears after a delay. In the case of the superhydrophilic GNP, the nanobubble is observed to grow explosively because it is initially generated at a distance from the GNP surface instead of on its surface. In the case of the superhydrophobic GNP, the faster generation of the nanobubble is promoted by the larger temperature difference between the GNP and the surrounding fluid and an ultrathin low-density layer that exists before the GNP is heated. For a given ß, faster generation and growth of nanobubbles are observed with increasing Q. Furthermore, the maximum radius of the nanobubble is found to be dependent on ß and not Q. The mechanism is elaborated based on the thermal resistance analysis at the melting point of GNPs. Additionally, it was found that there exists a threshold Q for nanobubble generation and the threshold value for the case of the superhydrophobic GNP is lower than that for the case of the superhydrophilic GNP. The present results have demonstrated that the superhydrophobic GNP is favorable for fast and energy-saving nanobubble generation. Our work provides further understanding in the generation and evolution of nanobubbles and potentially offers a new insight for nanobubble manipulation.

Dependences of Formation and Transition of the Surface Condensation Mode on Wettability and Temperature Difference.

In this work, we use molecular dynamics (MD) simulations to investigate the dependences of formation and transition of surface condensation mode on wettability (ß) and vapor-to-surface temperature difference (ΔT). We build a map of different surface condensation modes against ß and ΔT based on plenty of MD simulation results and reveal five formation mechanisms and two transition mechanisms. At low ß and ΔT, the high free energy barrier (ΔG*) prevents any surface clusters from surviving, therefore no-condensation (NC) is observed. The formation of dropwise condensation (DWC) could evolve from either nucleation or film rupture. Similarly, the formation of filmwise condensation (FWC) could evolve from either nucleation or the adsorption-induced film. The transition between NC and DWC is determined by ΔG* according to classical nucleation theory. The transition between DWC and FWC depends on the stability of condensate film; there emerges the competition between the trend that the uneven condensate film contracts and ruptures to droplets favored by lower ß and the trend that the uneven condensate film continues growing promoted by higher ΔT. We finally present a schematic overview of all of the mechanisms revealed for a better understanding of the physical phenomenon of the surface condensation mode.

lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation, metastasis and epithelial-mesenchymal transition in bladder cancer.

Bladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss-of-function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial-mesenchymal transition-related mRNA and protein levels of ZEB1, Snail, N-cadherin, and vimentin, with an increase in E-cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.

Polarized retinal pigment epithelium generates electrical signals that diminish with age and regulate retinal pathology.

The transepithelial potential difference (TEP) across the retinal pigment epithelial (RPE) is dependent on ionic pumps and tight junction "seals" between epithelial cells. RPE cells release neurotrophic growth factors such as pigment epithelial derived factor (PEDF), which is reduced in age-related macular degeneration (AMD). The mechanisms that control the secretion of PEDF from RPE cells are not well understood. Using the CCL2/CX3CR1 double knockout mouse model (DKO), which demonstrates RPE damage and retinal degeneration, we uncovered an interaction between PEDF and the TEP which is likely to play an important role in retinal ageing and in the pathogenesis of AMD. We found that: (a) the expression of ATP1B1 (the Na+ /K+ -ATPase ß1 subunit) was reduced significantly in RPE from aged mice, in patients with CNV (Choroidal Neovascularization) and in DKO mice; (b) the expression of PEDF also was decreased in aged persons and in DKO mice; (c) the TEP across RPE was reduced markedly in RPE cells from DKO mice and (d) an applied electric field (EF) of 50-100 mV/mm, used to mimic the natural TEP, increased the expression and secretion of PEDF in primary RPE cells. In conclusion, the TEP across the RPE depends on the expression of ATP1B1 and this regulates the secretion of PEDF by RPE cells and so may regulate the onset of retinal disease. Increasing the expression of PEDF using an applied EF to replenish a disease or age-reduced TEP may offer a new way of preventing or reversing retinal dysfunction.

Endogenous bioelectric currents promote differentiation of the mammalian lens.

The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and ß1 subunits of Na+ /K+ -ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem ). In contrast, differentiating, nucleated lens fiber cells had little ATP1A1 and ATP1B1 and a depolarized Vmem . Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lens epithelial cells to lie perpendicular to the direction of the EF. An EF also promoted the expression of ß-crystallin, aquaporin-0 (AQP0) and the Beaded Filament Structural Protein 2 (BFSP2) in lens epithelial cells (LECs), all of which are hallmarks of differentiation. In addition, applied EF activated the AKT and CDC2 and inhibition of AKT reduced the activation of CDC2. Our results indicate that the endogenous bioelectrical signal at the lens equator promotes differentiation of LECs into denucleated lens fiber cells via depolarization of Vmem. Development of methods and devices of EF application or amplification in vivo may supply a novel treatment for lens diseases and even promote regeneration of a complete new lens following cataract surgery.

[Application of Low Concentration Contrast Agent Combined Double Low Dose in CT Pulmonary Angiography for Pulmonary Embolism].

OBJECTIVE: To investigate the feasibility of low concentration contrast agent combined double low dose in CT pulmonary angiography. METHODS: 60 patients with clinically suspected pulmonary embolism examed by CT pulmonary angiography (CTPA) were divided into two groups (experimental group: n=30,80 kV, 15 mL,320 mg I/mL;control group: n=30,120 kV,50 mL,370 mg I/mL). The average CT value of main right and left pulmonary arteries,lobar arteries was calculated. Imaging post processing techniques included curved plannar reconstruction (CPR),volume rendering (VR) and maximal intensity projection (MIP). The artifact of the remaining contract in the superior vena cava and overall quality of the image were observed and analyzed by two senior doctors who were double blinded. RESULTS: All patients in two groups completed CTPA successfully. The image qualities of two groupssatisfy clinical diagnostic requirements and no difference of the image qualities was observed between two groups (P>0.05). The evaluation of venous pollution in experimental group was better than that of control group (P<0.01).No difference of CT values were observed between two groups [experimental group (423.2±89.4) HU,control group (465.7±85.6) HU](P>0.05). The SNR and CNR in experimental group were lower than those in control group (P<0.01 both).The CT dose index volume (CTDIvol),dose-length product (DLP) and size-specific dose estimates (SSDE) in experimental group were significantly lower than those incontrol group (P<0.01 all). CONCLUSION: The low concentration contrast agent combined double low dose in CT pulmonary angiography satisfies clinical diagnostic requirements. It has good clinical value for it could reduce venous pollution,iodine contrast agent and radiation exposure.

The Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress.

To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc.

Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway.

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.

[Clinical Study of Rs-EPI DWI to Improve Imaging Quality and Assessment on Intracranial Mass Lesions].

OBJECTIVES: To explore the clinical value of readout-segmented echo planar imaging (Rs-EPI) sequence in the assessment of intracranial mass lesions compared to the standard single-shot EPI (Ss-EPI) sequence. METHODS: We included 21 patients with intracranial mass lesions who underwent both Ss-EPI diffusion weighted imaging (DWI) and Rs-EPI DWI at 3.0T MR scanner with a twenty-channel head-neck coil. The quality of images was assessed by two experienced radiologists independently. The differences in image quality between two sequences were analyzed using Wilcoxon signed-rank test. Inter-observer agreements were analyzed using interclass correlation coefficient (ICC) and Kappa test. RESULTS: All objectives were completed on 3.0T MR. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in Rs-EPI DWI were higher than those in Ss-EPI DWI (130.46±49.10 vs. 71.58±30.43, P=0.000; 33.22±18.86 vs. 17.92±18.72, P=0.003). The scores of overall image quality, ghost artifact where next to the paranasal sinuses, mastoid air cells and frontal sinus of Rs-EPI DWI were significantly higher than those of Ss-EPI DWI. Meanwhile, the geometric distortion of anatomical structures of Rs-EPI DWI were significantly lower compared to Ss-EPI DWI sequence (0.016±0.021 vs. 0.037±0.069, P=0.00). The inter-reader and intra-reader agreements for the assessment of qualitative parameters were good [0.74≤Kappa value or ICC≤0.92]. CONCLUSIONS: Rs-EPI DWI sequence is a potential technique to improve the imaging quality in the diagnosis of intracranial mass lesions.

Catalysis of Extracellular Deamination by a FAD-Linked Oxidoreductase after Prodrug Maturation in the Biosynthesis of Saframycin†A.

The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM-A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however, the follow-up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane-bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase covalently associated with FAD, subsequently performs an oxidative deamination extracellularly. These results not only fill in the missing steps of SFM-A biosynthesis, but also reveal that a FAD-binding oxidoreductase catalyzes an unexpected deamination reaction through an unconventional extracellular pathway in Streptmyces bacteria.

Polarizing intestinal epithelial cells electrically through Ror2.

The apicobasal polarity of enterocytes determines where the brush border membrane (apical membrane) will form, but how this apical membrane faces the lumen is not well understood. The electrical signal across the epithelium could serve as a coordinating cue, orienting and polarizing enterocytes. Here, we show that applying a physiological electric field to intestinal epithelial cells, to mimic the natural electric field created by the transepithelial potential difference, polarized phosphorylation of the actin-binding protein ezrin, increased expression of intestinal alkaline phosphatase (ALPI, a differentiation marker) and remodeled the actin cytoskeleton selectively on the cathode side. In addition, an applied electric field also activated ERK1/2 and LKB1 (also known as STK11), key molecules in apical membrane formation. Disruption of the tyrosine protein kinase transmembrane receptor Ror2 suppressed activation of ERK1/2 and LKB1 significantly, and subsequently inhibited apical membrane formation in enterocytes. Our findings indicate that the endogenous electric field created by the transepithelial potential difference might act as an essential coordinating signal for apical membrane formation at a tissue level, through activation of LKB1 mediated by Ror2-ERK signaling.

Recurrent deletions of ULK4 in schizophrenia: a gene crucial for neuritogenesis and neuronal motility.

Although many pathogenic copy number variations (CNVs) are associated with neuropsychiatric diseases, few of them have been functionally characterised. Here we report multiple schizophrenia cases with CNV abnormalities specific to unc-51-like kinase 4 (ULK4), a serine/threonine kinase gene. Deletions spanning exons 21-34 of ULK4 were present in 4 out of 3391 schizophrenia patients from the International Schizophrenia Consortium, but absent in 3181 controls. Deletions removing exons 33 and 34 of the large splice variant of ULK4 also were enriched in Icelandic schizophrenia and bipolar patients compared with 98,022 controls (P = 0.0007 for schizophrenia plus bipolar disorder). Combining the two cohorts gives a P-value less than 0.0001 for schizophrenia, or for schizophrenia plus bipolar disorder. The expression of ULK4 is neuron-specific and developmentally regulated. ULK4 modulates multiple signalling pathways that include ERK, p38, PKC and JNK, which are involved in stress responses and implicated in schizophrenia. Knockdown of ULK4 disrupts the composition of microtubules and compromises neuritogenesis and cell motility. Targeted Ulk4 deletion causes corpus callosum agenesis in mice. Our findings indicate that ULK4 is a rare susceptibility gene for schizophrenia.

The expression of Cullin1 is increased in renal cell carcinoma and promotes cancer cell proliferation, migration, and invasion.

Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of renal cell carcinoma (RCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 307 cases of RCC tissues and 34 normal renal tissues. The Cul1 expression was increased significantly in RCC and was correlated with renal carcinoma histology grade (P = 0.007), tumor size (P = 0.013), and pT status (P = 0.023). Also, we found that silencing of Cul1 leads to increased expression of p21 and p27 that could inhibit the cyclin D1 and cyclin E2 expressions and arrest cell cycle at the G1 phase. Furthermore, knockdown of Cul1 inhibits RCC cell migration and invasion abilities by up-regulating the expression of TIMP-1 which could inhibit the expression of MMP-9. Finally, using bioluminescence imaging, we found that Cul1 knockdown significantly reduced the tumor growth in vivo. Cul1 may constitute a potential therapeutic target in RCC.

Comparison of Treatment Outcomes of Different Spermatic Vein Ligation Procedures in Varicocele Treatment.

In this study, 4 different spermatic vein ligation procedures for varicocele (VC) treatment were compared based on recurrence rate, postoperative complications, and semen quality. Between January 2012 and May 2013, a total of 345 male patients with VC were recruited at The First Affiliated Hospital of Soochow University. Patients were performed by different ligation procedures, and they were divided into 4 groups: laparoscopic varicocelectomy group (LV group: n = 84), microscopic inguinal varicocelectomy group (MIV group: n = 85), microscopic retroperitoneal varicocelectomy group (MRV group: n = 86), and microscopic subinguinal varicocelectomy group (MSV group: n = 90). In MSV group, the operative time was 55 ± 6.9 minutes, which was significantly longer than LV, MIV, and MRV groups (P < 0.05). Recurrence rate in LV group was at 11.9%, the highest rate observed compared with the MIV, MRV, and MSV groups (P < 0.05). Scrotal edema and testicular atrophy in MSV group were markedly decreased (P < 0.05), and scrotal pain was relieved in almost all patients in the MSV group at a significantly higher rate than LV, MIV, and MRV groups (P < 0.05). Sperm concentration, sperm count of grades a + b, and sperm motility (%) in the MSV group were sharply higher than LV, MIV, and MRV groups (all P < 0.05). Our study indicates that MSV is the most beneficial of the 4 spermatic vein ligation procedures and may be offered as the first-line treatment for VC in infertile men.