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Clarifying the time-dependent strength deterioration characteristics of carbonaceous mudstone under dry and wet cycles is of great significance to the design of expressway cut slopes. In this work, we conducted triaxial compression creep tests on carbonaceous mudstone specimens that had undergone different numbers of dry and wet cycles to investigate their creep properties. A function was established between the steady-state viscoplastic creep rate and axial compression. The threshold stress of the steady-state viscoplastic creep rate was assumed as the long-term strength, and the long-term strength deterioration law of carbonaceous mudstone under dry and wet cycles was studied. The results showed that the transient strain, viscoelastic creep, and viscoplastic creep of carbonaceous mudstone increased with the number of dry and wet cycles, and the creep failure stress and transient elasticity modulus decreased. Based on the steady-state viscoplastic creep rate method, the long-term strength of carbonaceous mudstone after n (n = 0, 3, 6, 9) dry and wet cycles was found to be 74.25%, 64.88%, 57.56%, and 53.16% of its uniaxial compression strength, respectively. Compared with the isochronous curve method and the transition creep method, the steady-state viscoplastic creep rate method can more accurately determine the long-term rock strength. The long-term strength of carbonaceous mudstone under dry and wet cycles decays exponentially, and the long-term strength decay rate during the first three dry and wet cycles is about 215 times the average decay rate.

KLF11 is a negative regulator of CSC stemness in sarcoma by repressing YAP/TEAD-dependent transcription., Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.

Although costunolide (Cos), a natural sesquiterpene compound isolated from various medicinal plants, exhibits antiproliferative and pro-apoptotic effects in diverse types of cancers, the mechanism associated with the anticancer property of Cos has not been elucidated. The present investigation was carried out to study the anticarcinogenic influence of Cos on kidney cancer cells. Several human renal cancer cell lines were used and biological and molecular studies were conducted. It was found that Cos significantly suppressed renal carcinoma cell growth via stimulation of apoptosis and autophagy in a concentration-dependent manner. Further studies revealed that Cos increased Bax/Bcl-2 ratio, decreased mitochondrial transmembrane potential (MMP), and enhanced cytoplasmic levels of cytochrome c, and activation of caspase-9, caspase-3, and cleaved PARP, resulting in cell apoptosis. The autophagy induced by Cos resulted from the formation of GFP-LC3 puncta and upregulation of LC3B II and Beclin-1 proteins. Compared with Cos treatment, the autophagy inhibitor 3-MA or ROS scavenger NAC significantly inhibited apoptosis and autophagy. Moreover, NAC and JNK-specific inhibitor SP600125 attenuated the effect of Cos. Taken together, Cos exerted autophagic and apoptotic effects on renal cancer through the ROS/JNK-dependent signal route. These findings suggest that Cos could be a beneficial anticarcinogenic agent.

Nobiletin, a flavonoid found chiefly in oranges and lemons, has exhibited potential anti-proliferative and pro-apoptotic activities in various types of cancers. However, the inhibitory effect and mechanisms of nobiletin on renal cancer cells are unclear. CCK8 and plate clone formation assay were used to determine the effect of nobiletin on the proliferation of renal cancer cells, while scratch healing test was used to assay its effect on migration ability. The effect of nobiletin on the invasion of renal cancer cells was determined using Trans well chamber assay. Flow cytometry was used to determine the effect of nobiletin on apoptosis of renal cancer cells, while Western blotting assay was used to determine its effect on the expressions of JAK2/STAT3 and PI3K/Akt pathway proteins, and apoptosis-related proteins. Nobiletin inhibited the proliferation of renal carcinoma cells in a time- and dose-dependent manner. It inhibited the migration and invasion of renal cancer cells, and promoted their apoptosis. Western blot results showed that nobiletin inhibited the phosphorylations of JAK2, STAT3, PI3K, and Akt, and promoted the expressions of apoptosis-related proteins. Nobiletin inhibits the proliferation, invasion and migration of renal cell carcinoma by inhibiting JAK2/STAT3 and PI3K/Akt pathways, and promotes their apoptosis. These findings provide a new experimental basis for the application of nobiletin in the treatment of renal cancer.

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immune-related genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.

To investigate the surgical techniques and clinical effect of Memokath transurethral spiral thermo-expandable prostatic stent (STEPS) implantation in the treatment of BPH.From January 2017 to January 2018, 26 BPH patients underwent Memokath transurethral STEPS implantation, 9 under the flexible cystoscope and the other 17 under the rigid cystoscope. The patients were aged 62－91 years old, with a prostate volume of 32－78 ml, postvoid residual urine volume (PVR) of (67.3 ± 11.2) ml, maximum urinary flow rate (Qmax) of (6.3 ± 1.8) ml/s, and IPSS score of 26.7 ± 5.7. Eight of the patients had preoperative urinary retention, of whom, 6 received catheterization and 2 had undergone cystostomy for bladder fistula before STEPS implantation.The operations lasted 15－30 minutes and were successfully completed in 24 cases while stent-shedding occurred in the other 2. Twenty-two of the patients achieved spontaneous urination immediately after surgery and 2 experienced bladder clot embolism. At 3 month after surgery, 24 of the patients showed significant improvement in PVR (［21.4 ± 7.7］ ml), Qmax (［18.3 ± 4.7］ ml/s) and IPSS (8.3 ± 2.1), and 13 exhibited no statistically significant difference from the baseline in the IIEF-5 score (14.1 ± 1.1 vs 14.3 ± 1.0, P0.05). At 12 months, all the patients were found with markedly improved urination but no adverse events except recurrent urinary tract infection in 2 cases.Memokath STEPS implantation, with its advantages of simple operation, high safety, definite effectiveness, non-influence on sexual function, is a new effective surgical option for the treatment of BPH.

Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer.We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC).Based on the RNA-seq data of 444 stage I-III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I-III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I-III ccRCC.Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival.Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03-1.75; p=0.028] to 1.89 [95% CI, 1.55-2.31; p0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II-III patients.The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I-III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management.The RCClnc4 classifier could facilitate patient management and treatment decisions.

New evidence suggests that microRNAs (miRNAs) play an important role in regulating the development and progression of prostate cancer. However, their specific functions and mechanisms remained to be further explored. MiR-129 has been reported in gastric cancers, colon cancer and lung cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in prostate cancer. The purpose of our study is to clarify the effects of miR-129 in cellular processes correlated with cancer development and progression of prostate cancer cell by regulating ETS1. MiR-129 and ETS1 expression in prostate cancer tissues, tumor adjacent tissues and cells were tested by quantitative real-time PCR. We validated the target relationship between miR-129 and ETS1 by dual luciferase reporter gene system. MTT, colony formation, tumorigenesis assays, flow cytometry, wound healing and transwell assays were used to analyze cell viability, proliferation, migration, and invasiveness in vivo and in vitro. The level of ETS1 protein expression was detected by western blot. Here we demonstrate that miR-129 have a relatively reduced expression in prostate cancer cell lines and tissues. Morever, the miR-129 inhibits the expression of ETS1 by binding its 3'-UTR. The overexpression of miR-129 can inhibit PC-3 cell viability, proliferation, migration and invasion through targeting ETS1 by PI3K/AKT/mTOR signaling pathway. These findings suggested that miR-129 could directly suppress ETS1, which might be one of potential mechanisms in inhibiting cell processes including viability, proliferation, migration and invasiveness of prostate cancercells and it provides new clues for us to understand the carcinogenesis of prostate cancer. In addition, it may help to develop a treatment approach for ETS1-activated prostate cancer.

To investigate the miRNA-21 over-expression in the acute kidney injury induced by sepsis, we developed a sepsis induced in vitro model by lip polysaccharide (LPS) and in vovo model by cecal ligation and puncture (CLP) surgery. LPS or CLP surgery induced kidney cell apoptosis increasing. However, the kidney injury indexes of miRNA groups which were transfected with miRNA-21 were significantly suppressed. In further study, the relative proteins expressions were evaluated to explain the miRNA-21 mechanism to improve sepsis induced kidney cell apoptosis. The results were shown that miRNA-21 over-expression had effects to protect kidney cell apoptosis induced by sepsis via PTEN/PI3K/AKT signaling pathway.

Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) in THP‑1 macrophage-derived foam cells. THP‑1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP‑1 macrophage-derived foam cells.

This work reports on a new impedimetric immunosensing strategy for sensitive detection of prostate-specific antigen (PSA) in biological fluids. The assay was carried out on monoclonal anti-PSA capture antibody-modified glassy carbon electrode with a sandwich-type detection format. Gold nanoparticles-decorated g-C3N4 nanosheets (AuNP/g-C3N4), synthesized by the wet-chemistry method, were utilized for the labeling of polyclonal anti-PSA detection antibody and horseradish peroxidase (HRP). Upon target PSA introduction, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Followed by the AuNP/g-C3N4, the labeled HRP could catalyze 4-choloro-1-naphthol into benzo-4-chlorohexadienone. The as-generated insoluble product was coated on the electrode surface, thus increasing the Faradaic impedance of Fe(CN)6(4-/3)(-) indicator between the solution and the base electrode. Under the optimal conditions, the impedance increased with the increasing target PSA in the sample, and exhibited a wide linear range from 10pgmL(-1) and 30ngmL(-1) with a detection limit of 5.2pgmL(-1). A repeatability and intermediate precision of

Phase field crystal model is used for studying the grain boundary premelting system under an applied strain at high temperature. The evolution of the dislocation configuration and proliferation and annihilation process of the dislocation and also the characteristic of the morphology of the premelting regions are observed. The results show that the extension premelting domain of the dislocation induced by the applied strain can be regarded as a new phase region (the softening crystal phase domain, SCPD). Due to the lattice softening of the SCPD, two alternant slipping systems exist in it. The cycle processes of the dislocation proliferation by blocking and annihilation by gliding in the SCPD can be regarded as two processes of dynamic recoveries. The evolution of the dislocation configuration and the microscopic mechanism of the cycle dynamic recovery-controlled dislocation at high temperature under plastic deformation in SCPD can well be revealed by the improved KM model.

In this work, the annihilation process of subgrain boundary (SGB) and splitting of low-angle symmetric till grain boundaries(GBs) during plastic deformation in the representatively system of these materials near but below the melting point and the temperature far from liquid-solid coexistence line are simulated using the phase filed crystals (PFC) model, respectively. The results show that premelting GBs at the temperature far from liquid-solid coexistence line will split into two SGBs and glide under strain. With the strain increasing, these SGBs of dislocations with opposite sign Burgers vectors are close to each other, and generate new grains to swallow up the old one. Finally these SGBs meet each other and annihilate, and then the SGBs and premelting regions disappear. The system with two grains transforms into that of one grain. The GBs at the temperature close to melting point under external exerting strain split into two SGBs with opposite sign dislocation, and move to approach other SGB split from other GB. The SGBs with opposite sign move close to each other at certain distance to form a dipole of dislocation pair in relative stability. Owing to the shear stress, the dislocation pair in the SGBs changes its direction two times, about 120°. After that, the SGBs move reverse to approach other opposite SGB, and appear to dislocation dissociation and transform into "Zigzag" shape of SGBs, and then the dissociated dislocation annihilates each other. For the premelting GB of the dislocation pair dipole under strain, it will start to extend and consolidate together, then decompose and separate from each other. In this process, the interaction of dislocation of different types occur, and also the generation of new dislocations and annihilation of dislocation by gliding, which will result in the change of Burgers vector of dislocation and the exchange of types of dislocation. The nature of this process is that the atomic lattices are softening inside the premelting region, which lead to the atomic array easily to gliding and torsional deformation under applying strain, and result in dislocation reaction in different types inside the premelting region and the change of Burgers vector of dislocation.

Prostate cancer (PCa) is one of the most prevalent diagnosed malignancies globally. Previous studies have demonstrated that prostaglandin E2 (PGE2) is closely associated with the tumorigenesis and progression of PCa. However, the underlying molecular mechanisms remain unclear and require further investigation. Matrix metalloproteinases (MMPs), receptor activator of nuclear factor‑κB ligand (RANKL) and runt‑related transcription factor 2 (RUNX2), which are involved in cell growth and bone metastasis, are frequently activated or overexpressed in various types of cancer, including PCa. The present study was designed to investigate the associations between PGE2 and the PGE2 receptor EP4, and MMPs, RANKL and RUNX2 in PCa, and to define their roles in PCa cell proliferation and invasion in addition to understanding the molecular mechanisms. The results of western blotting and reverse transcription‑quantitative polymerase chain reaction demonstrated that the protein and the mRNA expression levels of MMP‑2, MMP‑9, RANKL and RUNX2 in PC‑3 cells were significantly upregulated by treatment with PGE2, respectively, and knockdown of these proteins blocked PGE2‑induced cell proliferation and invasion in PC‑3 cells, as determined by Cell Counting Kit‑8 and Matrigel invasion assays, respectively. The effect of PGE2 on the protein and mRNA expression levels was primarily regulated via the EP4 receptor. EP4 receptor signaling activates the cyclic (c)AMP‑protein kinase A (PKA) signaling pathway, and forskolin, an activator of adenylate cyclase (AC), exhibited similar effects to an EP4 receptor agonist on the protein expression, while SQ22536, an inhibitor of AC, inhibited the protein expression. These results confirmed that the AC/cAMP pathway may be involved in EP4 receptor‑mediated upregulation of protein expression. By using a specific inhibitor of PKA, it was also demonstrated that cAMP/PKA was also involved in the EP4 receptor‑mediated upregulation of protein expression. In addition to the signaling pathway involving PKA, the EP4 receptor also exerts activities through activation of Akt kinase. The results in the present study confirmed the hypothesis that EP4 receptor‑mediated protein expression in PCa cells that were pretreated with a specific inhibitor of phosphatidylinositol 3‑kinase (PI3K) was significantly inhibited. In conclusion, the results of the present study indicate that PGE2 significantly upregulated the mRNA and protein expression levels of the MMP‑2, MMP‑9, RANKL and RUNX2, and the EP4 receptor was involved in the cell proliferation and invasion of PCa via the cAMP‑PKA/PI3K‑Akt signaling pathway. These results may provide novel insight into potential therapeutic strategies for the prevention and treatment of PCa.

Long non‐coding RNAs (lncRNAs) are non‐protein‐coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/β‐catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/β‐catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/β‐catenin signalling pathway‐related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/β‐catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/β‐catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/β‐catenin signalling pathway may be a feasible therapeutic method in the future.

The phase field crystal (PFC) model is used to simulate the premelting dislocation movement of the symmetric tilt grain boundary (STGB) under strain action when the system temperature is at far from the melting point and close to the melting point, respectively. The results show a local premelting occurs surrounding the dislocations as the premelting temperature is approached to from below temperature. The premelting dislocations of the STGB can glide under strain action, and the premelting region is a companion for dislocation gliding. The process of STGB decay is very similar at the two high temperature conditions. As premelting presents, it diminishes the gliding resistance for the dislocations and leads to a faster movement of dislocations, and also brings about more energy reduction of the system during the decay process of STGB. In spite of applying strain to these premelting samples in whole decay processes of STGB, the premelting dislocation region does not obviously develop and extend. This indicates that the external strain action does not promote the premelting at the high temperature, and cannot induce more premelting dislocation, which can be owed to the premelting phase around the dislocation exhibit fluid-like properties and to the premelting dislocation easily gliding and relaxing the strain energy; this is in agreement with the results of experiments and molecular dynamics.

The two-mode phase field-crystal (PFC) method is used to simulate the nanograin growth, including the grain growth in different sets of crystal planes, the grain boundary structure with mismatch, the grain orientation and also the incoherent grain boundary in two dimensional plane. It is obviously observed that there are dislocation structures in nanograin boundary due to mismatch and misorientation of grains. These simulation results can not only be used in artificial controlling the grain boundary of nanograin, but also is of significant for designing new nanograin with a good grain boundary for structure materials.

The second phase nucleation and precipitation around an edge dislocation are studied using phase field method. A new free energy function including the elastic strain energy is established to describe the dislocation interaction with the solute. The results give the distribution of strain field of dislocation and show the precipitates grow up according to the power growth law with the index 2. The simulated results are in good agreement with that of theory of non-uniform nucleation.

The phase field method was applied to study the effect of second-phase particles (SPP) with different geometric orientations and shapes on grain growth. The results show that, in the grain growth process, most of the spherical second-phase particles located at triple junctions, while the stick SPPs located at the grain boundaries along the grain boundary. The second-phase particles are of the strong pinning effect on grain boundary and the limiting grain radius can be expressed by Zener relations. In the condition of the second-phase particles area fraction and size remaining the same, the stick SPPs are of more effective pinning on grain growth than that for spherical SPPs, and the orientation of disk second-phase particles is also an influence factor for pinning effect. Stick second-phase particles with multiple orientations can make a better pining effect than those with only one orientation.

Background MicroRNAs, as a class of small, well-conserved, non-coding RNAs, are increasing identified as diagnostic biomarkers in many cancers. The dysregulated microRNA-129 (miR-129) is closely related with tumorigenesis and cancer progression. However, their potential role of miR-129 in prostate cancer still remains largely elusive. Aim In this study, we aimed to investigate the evidence of miR-129 as prognostic biomarkers for tumor progression and clinical prognosis in prostate cancer patients. Results The prostate cancer tissues exhibited a significant reduction in miR-129 expression compared with the paracancerous tissues (P

Background Renal cell carcinoma (RCC) is the most common kidney cancer in adults prognosis. Increasing appreciation of cell heterogeneity and a challenging disease with poor within clear cell renal cell carcinoma (ccRCC) has focused attention on a distinct subpopulation of cells called tumour initiating cells (T-ICs) or cancer stem cells (CSCs) in ccRCC. T-ICs exhibit extended self-renewal potential and tumour initiating ability. Tumours that harbour an abundant T-IC population or have high expression of stemness-related genes may signal a poor clinical outcome in RCC patients. Therefore, identification of the underlying mechanisms governing renal T-ICs propagation may lead to the discovery of promising therapeutic strategies for RCC patients. Methods Long non-coding RNA (lncRNA) is a subgroup of transcripts with more than 200 nt and limited coding potential. lncRNAs modulate biological process via diverse mechanisms, including mobilizing transcriptional co-regulators or chromatin-modifying complex at transcription level, and interacting with RNAs and protein complex or modifying signal proteins at post-transcription level. Several lncRNAs have been reported to regulate the self-renewal of T-ICs especially liver T-ICs. Nevertheless, the role of lncRNA in the regulation of renal T-ICs remains unknown. lncARSR (lncRNA Activated in RCC with Sunitinib Resistance, ENST00000424980) was a newly identified lncRNA to promote the sunitinib resistance of RCC in our previous study. Accumulating evidence indicated that T-ICs surviving from drug therapy and giving rise to tumour regrowth might be a major culprit for therapeutic resistance. Indeed, the expression signature of stem cell or targets of Nanog, Oct4, Sox2 and c-Myc (NOSM) in human ESCs were significantly enriched in our mRNA profile of sunitinib-resistant RCC cells (GSE69535), prompting us to explore the role of lncARSR in renal T-ICs. Results In this study, we first find that lncARSR is highly expressed in primary renal T-ICs and predicts poor prognosis. Next, by using loss-of-function analysis in T-ICs and gain-of-function analysis in RCC cells, we demonstrate that lncARSR promotes the self-renewal capacity, tumorigenicity and metastasis of renal T-ICs. Further mechanism study reveals that lncARSR interacts with Yes-associated protein (YAP) to block its phosphorylation by LATS1, facilitating YAP nuclear translocation. Interestingly, we find that YAP in turn promotes the transcription of lncARSR, forming a feed-forward loop. Clinical investigation also confirms the correlation between lncARSR and YAP, and demonstrates the value of combining lncARSR and YAP to improve the prognostic accuracy for RCC patients. Conclusions Altogether, we discover that lncARSR promotes the expansion of renal T-ICs via interacting with YAP.

Background The incidence of renal cell carcinoma (RCC) has been rising throughout the world. Approximately 20% of RCC patients presented with advanced stage disease at the time of diagnosis, and in patients with localized RCC, nearly 30% will develop recurrence and metastasis after tumor resection. Recently, improved comprehension of RCC pathogenesis led to the development of receptor tyrosine kinase (RTK) inhibitors, such as sunitinib, as the mainstay of therapeutic options for advanced RCC patients. Sunitinib is an oral multi-targeted RTK inhibitor, which has potent anti-angiogenic effects and direct anti-tumor activities due to the inhibition of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptors (PDGFR), stem-cell growth factor receptor (KIT) and FMS-like tyrosine kinase 3 (FLT3). However, 10–20% of advanced RCC patients are inherently refractory to sunitinib therapy, and most of the remaining patients end up with drug resistance and tumor progression after 6–15 months of therapy, resulting in failure of sunitinib to efficiently prolong the survival of RCC patients. Several studies have proposed the activation of compensatory signaling pathways for the acquisition of sunitinib resistance, but the picture remains unclear. On the other hand, few prognostic factors have been validated as predictive biomarkers of sunitinib response. Thus, it is urgent to elucidate the underlying mechanisms of sunitinib resistance and discover reliable biomarkers that can predict sunitinib response in RCC patients. Methods Exosomes can be secreted from multiple types of cells and participate in intercellular communication by transmitting intracellular cargoes, such as proteins and nucleic acids. Increasingly, some studies have suggested that exosomes from stromal cells could potentially affect therapeutic response though transfer of proteins and miRNAs. However, whether exosomes derived from resistant cancer cells can confer drug resistance to sensitive cells needs to be illustrated. Moreover, components embedded in circulating exosomes may serve as easily accessible biomarkers for the evaluation of drug response in patients. Long non-coding RNA (lncRNA) is a heterogeneous class of transcripts with a minimum length of 200 bases and without protein-coding potential. lncRNAs are involved in multilevel regulation of gene expression, including transcriptional regulation by recruiting chromatin-modifying complexes and post-transcriptional regulation by interacting with miRNAs, mRNAs or proteins. Emerging evidence supports the notion that lncRNAs modulate numerous hallmarks of cancer, including proliferation, apoptosis, metastasis and metabolism. However, the roles of lncRNAs in sunitinib resistance are poorly understood. In this study, we identify an upregulated lncRNA (lncARSR) in sunitinib-resistant RCC cells. We then investigate the contributions of lncARSR to sunitinib resistance and its therapeutic implications for sunitinib-resistant RCC patients. Results Herein we identified an lncRNA, named lncARSR (lncRNA Activated in RCC with Sunitinib Resistance), that correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids (LNA) targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response. Conclusions lncARSR may serve as a predictor and a potential therapeutic target for sunitinib resistance.

Background To summarize our clinical experience and review our technique of retroperitoneal robotic-assisted laparoscopic partial nephrectomy (RALPN) in management of T1b renal carcinoma. Assess the clinical efficacy and safety of retroperitoneal RALPN. Methods Retrospective review of 52 T1b renal carcinoma patients underwent retroperitoneal RALPN form January 2014 to October 2016. The patients included 30 males and 22 females, with an average age of (55.2±9.5) years old. There were 32 tumors in the left and 20 in the right. The mean lesion diameter was 4.5±0.7 cm. Results All cases were performed successfully. The operation was completed in a mean of 80.5±12.3 min, the mean warm ischemia time was 17.4±5.1 min, the mean blood loss was 38.2±7.4 mL and the mean extubation time was 2.1±0.7 d. Postoperative pathology reported malignant tumor in all cases, including renal clear cell carcinoma in 45 cases, papillary renal cell carcinoma in 5 cases and chromophobe cell carcinoma in 2 cases. The surgical margin of all cases were negative. Conclusions Retroperitoneal RALPN is an effective, safe and minimally invasive surgical management for T1b renal carcinoma.

Background Prostate cancer (PCa) is one of the most prevalent diagnosed malignancies in the world. Previous studies have proved that prostaglandin E2 (PGE2) was closely related to the tumorigenesis and progression of PCa. However, the molecular mechanisms are not very clear, and it is necessary to be further studied. MMPs, RANKL and RUNX2, involved in the cell growth and bone metastasis, are activated or overexpressed in many cancers, including PCa. Methods This study was designed to demonstrate the internal relationship and molecular mechanisms among the PGE2, EP4 and MMPs, RANKL and RUNX2 in PCa, and to define their roles in PCa cell proliferation and invasion. Results The results in this study showed that the protein and the mRNA expression levels of the MMP-2, MMP-9, RANKL and RUNX2 in PC3 cells were significantly upregulated by treated with PGE2, and knockdown of these proteins blocked PGE2-induced cell proliferation and invasion in PC3 cells. The effect of PGE2 on the protein and mRNA expression levels was mainly regulated via the EP4 receptor. EP4 receptor signaling activated cAMP-PKA signaling pathway, and forskolin, the activator of the adenylate cyclase (AC), has similar effects of the EP4 receptor agonist on the protein expression, while SQ22536, the inhibitor of AC, inhibited the protein expression. These results confirmed the AC/cAMP pathway was involved in EP4 receptor-mediated protein expression upregulation. By using specific inhibitor of PKA, it is demonstrated that cAMP/PKA was also related to the upregulation of the EP4 receptor-mediated protein expression. In addition to the signaling pathway of the PKA, the EP4 receptor also exerts activities through activating Akt kinase. The results in present study confirmed the hypothesis that the EP4 receptor-mediated protein expression of PCa cells, which were pretreated with the specific inhibitor of PI3K, was significantly inhibited. Conclusions In summary, it is revealed that PGE2 significantly upregulates the mRNA and protein expression levels of the MMPs, RANKL and RUNX2, and the EP4 receptor was involved in the cell proliferation and invasion of PCa via the cMAP-PKA/PI3K-AKT signaling pathway in this study. The present study may provide a new way of thinking and therapeutic strategy for the prevention and treatment of PCa.

Background Bone metastasis is one of the most common complications in clinical intractable castration-resistant prostate cancer (CRPC) and advanced prostate cancer period. The invasion ability of cancer cells was thought to have important relationship with the potential of cancer metastasis. EP4 receptor is overexpressed in several cancers, and enhanced EP4 receptor signaling has been previously shown to correlate with the invasion of several different cancer types. In present study, we found that EP4 antagonist can in vitro suppress the invasion phenotype abilities of CRPC PC3 cells, LNCaP cells with EP4 overexpressed which have the tendency to castration-resistance and in vivo suppress the CRPC bone metastasis animal models. Methods RNA interference was used to stably transfected EP4 to LNCaP with the pcDNA3.1-EP4, so as to be the LNCaP with vector control (LNCaP-mock) and LNCaP with EP4 overexpressed (LNCaP/EP4+) as described in our previous article. Effect on cell proliferation was determined firstly by the MTT assay. Transwell invasion assay was used to in vitro examine the metastasis abilities of PC3 cells, LNCaP cells, LNCaP/EP4+ and all after EP4 antagonist affected. Cells with ONO-AE3-208 at the final concentration of 0.1, 1 and 10 µmol/L were administrated to be the experimental group. To observe the effect of EP4 antagonist on the bone metastasis of prostate cancer in vivo, PC3/Luc cells were inoculated into the left cardiac ventricle of 5-week-old male nude mice. The mice developed osteolytic lesions with a mean endpoint at 52±7 days. To assess whether EP4 antagonist suppresses bone metastasis, ONO-AE3-208 (10 mg/kg/d) was given to the animals 5 days a week i.p. which the same volume of DDW was given as the control. To detect PC3 cell dissemination, bioluminescent imaging (BLI) was applied using a cooled CCD camera. We evaluated the efficacy of ONO-AE3-208 by measuring the photon counts of the metastatic lesions in the mandible and both hip joints in a blinded manner. Results The invasion assay showed that ONO-AE3-208 can inhibit the invasive abilities of both PC3 and LNCaP/EP4+ in a dose-dependent manner (P

Background To describe our experiences on robot-assisted laparoscopic radical prostatectomy (RALRP) for patients treated with transurethral resection of prostate (TURP) previously. Methods The clinical data of 14 patients who underwent RALRP after previous TURP between March 2012 and March 2017 at our hospital were retrospectively analyzed. All patients were followed-up about 4–64 months. Patients’ mean operation time, mean blood loss, mean postoperative catheter retained time, mean hospitalization time, complications, micturition control and oncologic outcome were comparatively reviewed. Results All cases were successfully performed through the abdominal cavity through the robotic surgical system. Mean operation time was (141±58) min. Mean blood loss was (198±220) mL, mean postoperative catheter retained time was (7.3±3.8) days, mean hospitalization time was (8.5±4.1) days. Three cases of postoperative pathology were positive, one patient was leaking urine after surgery, and no lymphatic leakage occurred. No distant metastasis occurred. One patient needed 1–2 pads per day after operation and the others were of urinary continence. Conclusions RALRP is an effective treatment for patients with prostate cancer who underwent previous TURP. It can be safely performed without compromising functional and oncology results. RALRP for patients treated with previous TURP is more difficult in technical performing than for patients without TURP treatment, because of the inflammatory response, tissue adhesion and continuity of the urethra caused by TURP.

Background The present study was designed to explore the clinical values of microRNA-129 (miR-129) expression in peripheral blood mononuclear cells for prostate cancer patients and the role of miR-129 in the proliferation of prostate cancer. Methods The peripheral blood mononuclear cells were isolated form blood simple from 98 patients confirmed with prostate cancer and 56 matched healthy volunteers. Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression level of miR-129 in peripheral blood mononuclear cells. Cox proportional hazards regression models and Kaplan-Meier analysis were used to evaluate the association of miR-129 expression with clinical and pathological characteristics of prostate cancer patients. The effect of miR-129 on the proliferation of prostate cancer cells in vitro was also determined. Results Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression of miR-129 was dramatically down-regulated in peripheral blood mononuclear cells for prostate cancer patients in comparison with healthy controls (P

Background To analyze the common causes of double J tube retention and to explore the safety and effectiveness of endoscopic minimally invasive management of double J tube retention. Methods The clinical data of 34 patients with difficult extubation of double J tube under conventional cystoscope from November 2012 to March 2018 in our center were retrospectively analyzed, including 22 cases of double J tube indwelling in the operation of upper urinary calculi and 12 cases due to ureteral stenosis and obstruction. Patients were diagnosed as double J tube retention according to the medical history, combined with abdominal plain tablets (KUB) plain film, total abdominal CT and other imaging findings. Among them, double J tube was located in the left side of ureter in 15 cases, right side in 15 cases, bilateral in 4 cases, with an average retention time of 10.64 months (0.5 to 72 months). The minimally invasive endoscopic technique was performed alone or in combination with cystoscopy, ureteroscopy and percutaneous nephrolithotomy. Results Seventeen cases with peri-tube stone formation and 10 cases of double J tube displacement resulting in retention and difficulty in extubation. Four patients had forgotten extubation after discharge. Two patients with severe urinary tract infection underwent stents replacement after anti infection treatment. One case of severe hematuria accompanied by bladder spasm led to failure of extubation. All stranded double J tubes were successfully removed, of which 14 cases were removed by ureteroscopy, 12 by cystoscopy or ureteroscopic lithotripsy, and 8 cases were removed by the combination of cystoscopy, ureteroscopy and percutaneous nephroscope. The average operation time was 68.5 minutes (14 to 275 minutes). No case was transferred to open surgery. Except for a small amount of hematuria, there were no severe complications such as ureteral perforation, laceration and nephrectomy. Two patients developed hyperthermia after operation and the body temperature returned to normal with active anti-infection treatment. Residual stones were found in 4 patients after operation. The average postoperative hospital stay was 2.7 days (1 to 12 days). Conclusions The peri-tube stone formation and displacement of double J tube after long term indwelling are the main reasons for the retention of double J tube. According to the patient’s condition, it is safe and effective to remove the stranded double J tube through minimally invasive endoscopic technique alone or in combination with cystoscopy, ureteroscopy and percutaneous nephroscopy. Moreover, it is necessary to strengthen the management of patients with double J tube indwelling, so as to avoid double J tube being left behind.

To compare robot-assisted laparoscopic radical prostatectomy (RALRP) with laparoscopic radical prostatectomy (LRP) in the treatment of prostate cancer and investigate the clinical application value of RLRP.We retrospectively analyzed 70 cases of prostate cancer treated by RALRP and another 32 cases treated by LRP. We compared the operation time, intraoperative blood loss and transfusion, catheter-indwelling time, postoperative hospital stay, incisal margin positive rate, biochemical recurrence, and normal postoperative urinary continence and penile erectile function between the two groups of patients.All the operations were successfully accomplished. RALRP exhibited a significant superiority over LRP in intraoperative blood loss and transfusion, catheter-indwelling time, and postoperative hospital stay, urinary continence and erectile function (P0.05).Robot-assisted laparoscopic radical prostatectomy, with its advantages of few postoperative complications and well-preserved urinary continence and penile erectile function, is an effective, safe and minimally invasive surgical option for prostate cancer.

Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-β (lncRNA-ATB) is a stimulator of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways.

MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding RNAs that are increasingly identified as diagnostic and prognostic biomarkers in a number of cancers. Deregulated miR‑129 is closely associated with tumorigenesis and cancer progression. However, the potential role of miR‑129 in prostate cancer remains largely elusive. The present study investigated the role of miR‑129 as a prognostic biomarker for tumor progression and clinical prognosis in prostate cancer patients. The examined prostate cancer tissues exhibited a significant reduction in miR‑129 expression compared with the normal tissues (P=0.013). The expression levels of miR‑129 were negatively correlated with histological grade (P

Objective This study aims to profile dysregulated microRNA (miRNA) expression in clear cell renal cell carcinoma (ccRCC) and to identify key regulatory miRNAs in ccRCC. Methods and Results miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452) and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p) in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429) were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3’ untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes. Conclusions This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429) may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

Objective To assess the efficacy of Xianlong Capsule (XLC) in treating senile vascular dementia (VD).

To examine the effect of ONO-AE3-208, an EP4 antagonist, on the formation of bone metastasis from prostate cancer in mice.Thirty-four 6-week old nude mice were divided into an experimental and a control group of equal number to be treated by intraperitoneal injection of ONO-AE3-208 and double distilled water, respectively. Then PC3/LUC cells were constructed by stably transfecting luciferin to prostate cancer PC3 cells and inoculated into the left ventricle of the mice to establish an animal model of systemic bone metastasis. The time of metastasis formation, photon tumor burdens, and changes of the survival curves after modeling were compared between the two groups of mice.At 30 days after modeling, bioluminescence imaging analysis showed that the photon tumor burdens were significantly increased in a time-dependent manner in the control group in comparison with those in the experimental group (P0.01). The rate of metastasis formation was significantly higher in the former than in the latter (93.3% vs 33.3%, P0.001). The median time of metastasis formation was 29 d (95% CI 26.547 - 35.262) in the experimental animals as compared with 21 d (95% CI 17.213 -24.787) in the controls (P0.001).EP4 antagonist ONO-AE3-208 can inhibit the formation of bone metastasis from prostate cancer in mice.

To investigate the effects of the downregulated expression of the prostate androgen regulated (PAR) gene on the cell cycle and apoptosis of PC3 cells as well as on the expression level of Bcl-2/Bax.After transfecting PC3 cells with small interfering RNA (siRNA) targeting PAR, we detected the inhibitory effect of PAR depletion on the proliferation of the PC3 cells by MTT assay, determined their apoptosis by flow cytometry, and measured the expression levels of Bcl-2 and Bax by Western blot.The expression of PAR was suppressed by siRNA, the G2-M phase PC3 cells were increased to (29.95 +/- 3.25)%, and the apoptosis of the cells was enhanced to (20.61 +/- 2.73)%, with statistically significant difference from the control group (P0.01). Western blot showed a decreased expression of Bcl-2, an increased expression of Bax, and an elevated ratio of Bax to Bcl-2.Downregulation of the PAR expression increases the Bax/Bcl-2 ratio and Bax expression, and thus induces the G2-M phase arrest and apoptosis of PC3 cells.

Background This study aims to profile dysregulated microRNA (miRNA) expression in clear cell renal cell carcinoma (ccRCC) and to identify key regulatory miRNAs in ccRCC. Methods miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Results Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452) and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p) in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429) were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3’ untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes. Conclusions This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429) may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

Background Renal-cell carcinoma (RCC) is resistant to almost all chemotherapeutics and radiation therapy. Wnt/β-catenin signaling plays an important role in RCC tumorigenesis, a drug targeting the Wnt signaling is likely to have therapeutic benefit. 15-oxospiramilactone is a new Wnt molecule inhibiter. In the present study, anti-tumor effects on RCC cells and the involved mechanisms were investigated. Methods Human RCC 786-0 and ACHN cells were treated with different concentrations of 15-oxospiramilactone, and cell viability, cell cycle and apoptosis were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Protein and mRNA expression were assayed by western blotting and quantitative real-time PCR (qPCR). Protein distribution and the association between proteins were assayed by Cytosol and nucleus fractionation and co-immunoprecipitation, respectively. Xenograft assay was used to examine the effect of 15-oxospiramilactone on renal cancer cell proliferation in vivo. Results 15-oxospiramilactone inhibited the viability of 786-0 and ACHN cells in a dose -dependent manner and it could also significantly suppress the growth of renal carcinoma xenografts and metastasis in nude mice. It also arrested RCC cells at G2/M phase of the cell cycle and induced cell apoptosis. Further study showed that 15-oxospiramilactone inhibited Top-flash reporter activity and decreased the mRNA and/or protein expression of Wnt target genes Axin2, LEF1, NKD1, Cyclin D1 and Survivin, as well as decreased the protein levels of Cdc25c and Cdc2. 15-oxospiramilactone did not affect the cytosol-nuclear distribution, but decreased β-catenin/TCF4 association in RCC cells. Conclusions Our data provide first evidence that 15-oxospiramilactone can inhibit cell proliferation in vitro and in vivo, arrest cell cycle at G2/M phase and induce cell apoptosis in RCC cells. The anti-tumor effect is associated with the inhibition of Wnt/β-catenin signaling in RCC cells. The new molecule may be a potential compound for treating renal cell carcinoma.

To study the causes, clinical manifestations, treatment and prevention of calculus that develops in the prostatic cavity after transurethral resection of the prostate.We reported 11 cases of calculus that developed in the prostatic cavity after transurethral resection or transurethral plasmakinetic resection of prostate. The patients complained of repeated symptoms of frequent micturition, urgent micturition and urodynia after operation, accompanied with urinary tract infection and some with urinary obstruction, which failed to respond to anti-infective therapies. Cystoscopy revealed calculi in the prostatic cavity, with eschar, sphacelus, uneven wound surface and small diverticula in some cases. After diagnosis, 1 case was treated by holmium laser lithotripsy and a second transurethral resection of the prostate, while the other 10 had the calculi removed under the cystoscope, followed by 1 -2 weeks of anti-infective therapy.After treatment, all the 11 cases showed normal results of routine urinalysis, and no more symptoms of frequent micturition, urgent micturition and urodynia. Three- to six-month follow-up found no bladder irritation symptoms and urinary tract infection.Repeated symptoms of frequent micturition, urgent micturition, urodynia and urinary tract infection after transurethral resection of the prostate should be considered as the indicators of calculus in the prostatic cavity, which can be confirmed by cystoscopy. It can be treated by lithotripsy or removal of the calculus under the cystoscope, or even a second transurethral resection of the prostate. For its prevention, excessive electric coagulation and uneven wound surface should be avoided and anti-infection treatment is needed.

To explore the feasibility of the treatment of hypospadias with penile and scrotal skin flaps.Twenty-three hypospadias patients aged 3.5-19 (mean 6. 8) years underwent urethroplasty with penile and scrotal skin flaps. All were followed up for 6 years and analyzed retrospectively.Of the total number of patients, 21 (91.3%) succeeded in one operation and the other 2 developed complications, including urethral fistula and urethral structure.Penile and scrotal skin, advantageous for its adequacy, rich blood supply and contribution to high success rate of surgery, is believed to be the first choice for urethroplasty in the treatment of hypospadias.

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

To observe clinical curative effect of Shenxiong Bushen Capsule for the treatment of mild vascular dementia (VaD), and probe the partial mechanism.With a block random, double-blinded and controled clinical research method adopted, seventy patients with VaD were randomly assigned to two groups in a ratio of 5:2, including 50 cases in the trial group and 20 cases in the control group. The patients in the trial group were given the Shenxiong Bushen Capsule (5 tablets, thrice a day), while those in the control group were given Piracetam (5 tablets, twice a day). All patients of the two groups were treated for 2 months, and one third cases were follow-up surveyed for 1 month. The cognitive ability, the activities of daily living, Chinese medicine syndrome of VaD, and the quality of life were measured respectively before and after the treatment.According to the Mini-Mental State Examination, the clinical effects of patients showed that there was insignificant difference between the trial group (total effective rate was 74.46% and 80.85%, respectively) and the control group (total effective rate was 68.42% and 78.95%, respectively) on the cognitive ability and the activities of daily living (P0.05), while the curative effect of the trial group (total effective rate was 85.11%) was superior to that of the control group (total effective rate was 63.16%) on Chinese medicine syndrome of VaD, and had significant difference between the two groups (P0.05). The results measured by WHOQOL-SF36 indicated that the total scores and the scores of each field in both the trial group and the control group after treatment increased more than those of before treatment (P0.01, P0.05), except physical function (PF) field and role physical (RP) field of the control group (P0.05). The scores of the trial group about total body, PF field, RP field and vitality (VT) field increased more than those of the control group (P0.05); while no difference was shown between the trial group and control group in the scores of bodily pain field, role emotional field, general health field, social function field and mental health field (P0.05).Shenxiong Bushen Capsule has a definite curative effect on mild VaD, and it can improve the quality of life of patients. Adopting the SF36 Scale to evalute the quality of life of patients with VaD has significance and avaibility to some extent.

To observe the clinical efficacy of modified Huanglian Wendan Decoction (HWD) in treating senile mild cognitive impairment (MCI) of turbid-phlegm blocking orifice syndrome.With a block randomized, double-blinded and controlled design adopted, the 64 patients of MCI selected from December 2007 to February 2009 were randomly and equally assigned to two groups. The treatment group was treated with HWD in dose of 200 mL, twice a day; the control group was given Aniracetam 0.2 g (for patients over 70-years-old, 0.1 g) three times a day. And the illusive medicine in dosage-form of capsule/decoction simulated to that used in the opposite group was applied. The medication and observation lasted for three months. Chinese medicine syndrome, cognition capacity (by MMSE), laboratory indexes [acetylcholine (Ach), superoxide dismutase (SOD), malondialdehyde (MDA)] and safety related indexes in patients were observed.After treatment, MMSE score increased in both groups, but the increment in the treatment group was significantly higher than that in the control group (P0.01); Chinese medicine syndrome estimated by scoring showed that after treatment, all scores of syndromes, excepting the expectoration, were improved in the treatment group with the post-treatment scores significantly lower than those in the control group respectively (P0.05 or P0.01); while in the control group, lowering of scores only showed in some symptoms such as poor memory, heavy head or dizziness, and heavy sensation in limbs and body. Serum levels of Ach and SOD decreased and MDA increased in both groups after treatment, but the change of Ach was more significant in the treatment group (P0.01). No obvious adverse reactions were found during the treatment.For treatment of MCI, HWD shows effects in improving patients' symptoms, cognition capacity and elevating serum Ach content better than that of Aniracetam; and with effects for raising SOD activity and reducing MDA level similar to those of Aniracetam.

To determine the clinicopathological characteristics, treatment and prognostic features of prostatic small cell carcinoma (SCC).One case of SCC was reported, and the relevant literature was reviewed and analyzed.Prostate specific antigen (PSA) was increased (39.26 ng/ml); computed tomography revealed multiple nodules in the retroperitoneum and cavita pelvis; ECT showed multiple osseous metastasis; and needle biopsy of the prostate confirmed SCC. Negative expressions of PSA, Bcl-2 and P504S were found by immunohistochemical staining. The cancer was clinically staged at T4N1M1. Because the patient was beyond surgery and refused chemotherapy, Zadaxin (thymosin alpha 1) was given to relieve the clinical symptoms. The patient died five months after the diagnosis.SCC is a rare subset of prostate cancer, with high malignancy, rapid growth, fast metastasis and very poor prognosis. Its diagnosis relies on pathological examinations. PSA cannot be a specific tumor marker of SCC, but some immunophenotypes may help its differential diagnosis. As for its treatment, surgery should be considered in the early stage; neither hormonal therapy nor chemotherapy can afford a favorable prognosis, although the latter may effect a short-term relief of the clinical symptoms.

To assess the safety of hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis in patients with prostate cancer, and to investigate its effect on the growth of indolent prostate cancer in vivo.Thirty severe combined-immunodeficient mice received subcutaneous injection of human prostate cancer LNCaP cells. Then they were randomized to an experimental and a control group and exposed to 20 sessions of hyperbaric oxygen and normobaric air, respectively, followed by a 4-week observation on the growth of the transplanted tumors and analyses of their histopathological features at 28 days, including the volume, microvessel density (CD34), apoptosis markers (p53 and p27 proteins) and the proliferation index (Ki-67) of the LNCaP tumors.On the 28th day after tumor vaccination, the tumor volume was (120 +/- 7.9) mm3 in the HBO and (122 +/- 8.2) mm3 in the control group; the microvessel density and the expressions of Ki-67, p53 and p27 were 39.3 +/- 5.2, (78.1 +/- 7.6)%, (40.4 +/- 6.2)% and (63.7 +/- 5.1)% in the former, and 36.2 +/- 4.9, (75.3 +/- 8.4)%, (44.2 +/- 5.7)% and (61.5 +/- 5.5)% in the latter. There were no significant differences in all the indexes above between the two groups (P0.05).Hyperbaric oxygen did not promote the growth of indolent prostate cancer in the murine model, nor did it have any significant effect on the new vessels.

To investigate the anti-tumor effect of the endothelin A receptor antagonist BQ123 on human prostate cancer cell line PC-3M in vitro by observing its impact on the proliferation and apoptosis of human prostate cancer cells.The inhibiting effect of BQ123 on the proliferation of PC-3M cells was observed by MTT assay, erosion trace test and Transwell chamber chemotaxis assay, and its induction of their apoptosis determined by Annexin V-FITC/PI staining and cytometry.BQ123 exhibited increased inhibition of PC-3M cells in a time-dependent manner, with inhibition rates of 22.32%, 44.88% and 64.47% at 24 h, 48 h and 72 h, respectively (P0.05). The migration distances of the PC-3M cells in the BQ123 group were (103.42 +/- 75.63) microm, (243.75 +/- 121.53) microm and (422.07 +/- 36.01) microm at 12 h, 24 h and 48 h, obviously lower than (162.93 +/- 19.87) microm, (317.19 +/- 43.19) microm and (692.74 +/- 40.84) microm in the control group (P0.05). The number of the PC-3M cells that invaded the inferior chamber in the BQ123 group was (79.2 +/- 9.58), significantly decreased as compared with (92.6 +/- 5.94) in the control (P0.05). The apoptosis rate of PC-3M exposed to BQ123 was (15.03 +/- 0.93)%, significantly higher than (9.38 +/- 1.37)% in the control (P0.05). The ratio of PC-3M cells in different cycles showed no significant differences.BQ123 inhibits the proliferation of PC-3M cells and induces their apoptosis in vitro, which may give a new idea on the studies of prostate cancer therapies.

To investigate the expressions of VEGF in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), their clinical significance and their relationship with that of ET-1.A total of 44 specimens of PCa and 36 of BPH tissues were examined by the immunohistochemical Elivision plus method for the expressions of VEGF and ET-1. The intensity of staining for VEGF and ET-1 was assessed by light microscopy on a scale from "-" to "+ + +".The rates of positive expression of VEGF were 69.4% in BPH and 80.9% in PCa, positive staining mostly in the cytoplasm of glandular epithelia and cancer cells, and strongly positive in all the stroma vascular endothelial cells. The staining intensity of VEGF was significantly higher in the PCa than in the BPH group (P0.05) , in the bone metastasis (BM) than in the non-BM group (P0.01), and in the lowly than in the highly and moderately differentiated PCa tissues (P0.01). The expression of VEGF was positively correlated with that of ET-1 ( r(s) = 0.780, P0.01).VEGF is involved in the development, progression and metastasis of PCa. VEGF and ET-1 may play a joint role in its development and progression.

Cyclooxygenase-2 (Cox-2) is over-expressed in prostate cancer (PCa) and involved in its development and progression by facilitating inflammatory response, reducing cell apoptosis, increasing angiogenesis and damaging DNA oxidation. Selective Cox-2 inhibitors suppress PCa growth through various channels and therefore have a promising application value in the management of prostate cancer.

To investigate the anti-tumor effect of celecoxib on human prostate cancer cell line PC-3 in vitroby observing its effects on the proliferation and apoptosis of PC-3 cells.The effects of Celecoxib on the proliferation of PC-3 cells were observed by MTT assay, erosion trace test and Transwell-chamber chemotaxis assay, and their apoptosis detected by Annexin V/FITC fluorescent staining and flow cytometry.With the increasing concentration and exposure time, Celecoxib exhibited an increased rate of inhibition on PC-3 cells in a dose- and time-dependent manner (P0.05). Compared with the controls, the migration distance of the PC-3 cells and the number of the PC-3 cells that invaded the inferior chamber were significantly decreased in the 100 gm/L Celecoxib group (P0.05). Celecoxib induced the apoptosis of PC-3 cells and, at 100 microm/L, significantly increased the percentage of PC-3 cells in the G0/G1 phase but decreased it in the S phase as compared with the control group (P0.05).Celecoxib inhibits the proliferation and induces the apoptosis of PC-3 cells in vitro, which, as a new therapeutic for prostate cancer, well deserves further investigation.

To investigate the different expressions of endothelin-1 ET-1) in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) tissues and their clinical significance.A total of 36 BPH and 44 PCa specimens were examined for the expression of ET-1 by immunohistochemical technique (Elivision plus method). The staining intensity for ET-1 was assessed by light microscopy on a scale from "-" to "+ + +".Positive immunoreactivity was found in BPH and PCa, with a positive rate of 100%. Positive staining was located mostly in the cytoplasm of glandular epithelia and smooth muscle cells of both BPH and PCa and was noted in all stroma vascular endothelial cells. These were no significant differences in the intensity of positive staining for ET-1 between the groups of BPH and PCa (P0.05), bone metastasis (BM) and non-BM (P0.05), and highly and moderately differentiated PCa (P0.05), but the staining intensity for ET-1 was significantly higher in the poorly than in the highly and moderately differentiated PCa (P0.01).ET-1 has a high expression and the localization is the same in both BPH and PCa. It is involved in the development and progression of BPH and PCa.