IIAM: Intra and Inter Attention with Mutual Consistency Learning Network for Medical Image Segmentation.

Medical image segmentation provides a reliable basis for diagnosis analysis and disease treatment by capturing the global and local features of the target region. To learn global features, convolutional neural networks are replaced with pure transformers, or transformer layers are stacked at the deepest layers of convolutional neural networks. Nevertheless, they are deficient in exploring local-global cues at each scale and the interaction among consensual regions in multiple scales, hindering the learning about the changes in size, shape, and position of target objects. To cope with these defects, we propose a novel Intra and Inter Attention with Mutual Consistency Learning Network (IIAM). Concretely, we design an intra attention module to aggregate the CNN-based local features and transformer-based global information on each scale. In addition, to capture the interaction among consensual regions in multiple scales, we devise an inter attention module to explore the cross-scale dependency of the object and its surroundings. Moreover, to reduce the impact of blurred regions in medical images on the final segmentation results, we introduce multiple decoders to estimate the model uncertainty, where we adopt a mutual consistency learning strategy to minimize the output discrepancy during the end-to-end training and weight the outputs of the three decoders as the final segmentation result. Extensive experiments on three benchmark datasets verify the efficacy of our method and demonstrate superior performance of our model to state-of-the-art techniques.

Gene expression profiling of venous malformations identifies the role of SDC1 in venous endothelial cells.

Objective: To obtain insight into the molecular process implicated in venous malformations (VMs) and identify potential targets for treatment of VMs, this study profiled the gene expression pattern in VMs, investigated alterations of syndecan-1 (SDC1) expression in VMs, and tested the hypothesis that aberrant SDC1 expression triggers abnormal angiogenesis and VM development. Methods: Microarray analysis was performed to identify differentially expressed genes (DEGs) on a transcriptome-wide level in VMs and conjunctive normal. Gene Ontology molecular functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out to establish enhancement of biological signaling pathways involved in VMs. Among the DEGs, we focused on SDC1, which is involved in matrix remodeling, cell proliferation and invasion, and angiogenesis. SDC1 expression in VMs was verified by qRT-PCR, western blotting, and immunohistochemistry. Loss-of-function of SDC1 was achieved in human umbilical vein endothelial cells (HUVECs) by siRNA to investigate the roles of SDC1 in cell migration, invasion, and angiogenesis. Results: Compared with control tissue, the transcriptome study identified 274 upregulated DEGs and 3 downregulated DEGs. The transcript and protein levels of SDC1 were significantly decreased in VMs compared with normal tissue. Inhibition of SDC1 enhanced HUVEC migration, invasion, and angiogenesis. Conclusion: Our genome-wide microarray analysis suggests the involvement of numerous genes in VMs. Among them, SDC1 plays a substantial role in the process of angiogenesis and development of VMs. SDC1 may represent a potential target for a molecular therapy for VMs.

Discovery of Pyridyl-Benzothiazol Hybrids as Novel Protoporphyrinogen Oxidase Inhibitors via Scaffold Hopping.

In order to discover novel protoporphyrinogen oxidase (PPO) inhibitors with excellent herbicidal activity, a series of structurally novel 6-(pyridin-2-yl) benzothiazole derivatives were designed based on the scaffold hopping strategy. The in vitro experiments demonstrated that the newly synthesized compounds exhibited noteworthy inhibitory activity against Arabidopsis thaliana PPO (AtPPO), with IC50 values ranging from 0.06 to 1.36 µM. Preliminary postemergence herbicidal activity tests and crop safety studies indicated that some of our compounds exhibited excellent herbicidal activity and crop safety. For instance, compound (rac)-7as exhibited superior herbicidal activities to commercially available flumioxazin (FLU) and saflufenacil (SAF) at all the tested concentrations and showed effective herbicidal activities even at a dosage as low as 18.75 g ai/ha. Meanwhile, compound (rac)-7as showed good crop safety for wheat at a dosage as high as 150 g of ai/ha. Although the absolute configuration of compound 7as has no obvious effect on its herbicidal activity, compound (R)-7as showed a slightly higher crop safety than compound (S)-7as. Molecular simulation studies of Nicotiana tabacum PPO (NtPPO) and our candidate compounds showed that the benzothiazole moiety of compounds (R)-7as or (S)-7as formed multiple π-π stacking interactions with FAD, and the pyridine ring generated π-π stacking with Phe-392. Our finding proved that the pyridyl-benzothiazol hybrids are promising scaffolds for the development of PPO-inhibiting herbicides.

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

Design, Synthesis, and Herbicidal Evaluation of Pyrrolidinone-Containing 2-Phenylpyridine Derivatives as Novel Protoporphyrinogen Oxidase Inhibitors.

In this work, a series of pyrrolidinone-containing 2-phenylpyridine derivatives were synthesized and evaluated as novel protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) inhibitors for herbicide development. At 150 g ai/ha, compounds 4d, 4f, and 4l can inhibit the grassy weeds of Echinochloa crus-galli (EC), Digitaria sanguinalis (DS), and Lolium perenne (LP) with a range of 60 to 90%. Remarkably, at 9.375 g ai/ha, these compounds showed 100% inhibition effects against broadleaf weeds of Amaranthus retroflexus (AR) and Abutilon theophrasti (AT), which were comparable to the performance of the commercial herbicides flumioxazin (FLU) and saflufenacil (SAF) and better than that of acifluorfen (ACI). Molecular docking analyses revealed significant hydrogen bonding and π-π stacking interactions between compounds 4d and 4l with Arg98, Asn67, and Phe392, respectively. Additionally, representative compounds were chosen for in vivo assessment of PPO inhibitory activity, with compounds 4d, 4f, and 4l demonstrating excellent inhibitory effects. Notably, compounds 4d and 4l induced the accumulation of reactive oxygen species (ROS) and a reduction in the chlorophyll (Chl) content. Consequently, compounds 4d, 4f, and 4l are promising lead candidates for the development of novel PPO herbicides.

Understanding the role of pathways in a deep neural network.

Deep neural networks have demonstrated superior performance in artificial intelligence applications, but the opaqueness of their inner working mechanism is one major drawback in their application. The prevailing unit-based interpretation is a statistical observation of stimulus-response data, which fails to show a detailed internal process of inherent mechanisms of neural networks. In this work, we analyze a convolutional neural network (CNN) trained in the classification task and present an algorithm to extract the diffusion pathways of individual pixels to identify the locations of pixels in an input image associated with object classes. The pathways allow us to test the causal components which are important for classification and the pathway-based representations are clearly distinguishable between categories. We find that the few largest pathways of an individual pixel from an image tend to cross the feature maps in each layer that is important for classification. And the large pathways of images of the same category are more consistent in their trends than those of different categories. We also apply the pathways to understanding adversarial attacks, object completion, and movement perception. Further, the total number of pathways on feature maps in all layers can clearly discriminate the original, deformed, and target samples.

Herbicidal Activity of Beflubutamid Analogues as PDS Inhibitors and SAR Analysis and Degradation Dynamics in Wheat.

In this work, a series of beflubutamid (BF) analogues' postemergent herbicidal activity was evaluated, and the structure-activity relationship (SAR) was discussed. At a dosage of 300 g ai/ha, compounds (Rac)-6h and (Rac)-6q showed excellent herbicidal activity against Amaranthus retroflexus, Abutilon theophrasti, and Medicago sativa, with inhibition rates of 90, 100, and 80% and 100, 100, and 100%, respectively, comparable to that of commercial herbicide BF, which showed inhibition rates of 90, 100, and 100%, respectively. Notably, at dosages of 150 and 300 g ai/ha, the chiral compounds (S)-6h and (S)-6q exhibited higher herbicidal activities than their racemates. Molecular docking results indicated that compounds (S)-BF and (S)-6h have stronger binding affinities with Oryza sativa phytoene desaturase (OsPDS), resulting in a higher herbicidal activity. Additionally, the degradation dynamics half-life of (S)-BF in wheat was determined to be 77.02 h. Consequently, compounds (S)-6h and (S)-6q are promising lead candidates for the development of highly effective herbicides.

NHC-Catalyzed Chemoselective Reactions of Enals and Cyclopropylcarbaldehydes for Access to Chiral Dihydropyranone Derivatives.

An N-heterocyclic carbene (NHC)-catalyzed chemoselective activation reaction of 1-cyclopropylcarbaldehydes and α-alkynyl enals is reported. NHC selectively catalyzes 1-cyclopropylaldehydes, followed by a [2 + 4] cycloaddition reaction with α-alkynyl enals. The target dihydropyranone derivatives bearing different substituents and substitution patterns can be obtained in good to excellent yields with excellent enantio- and diastereoselectivities under mild conditions.

Self-Adaptive Graph With Nonlocal Attention Network for Skeleton-Based Action Recognition.

Graph convolutional networks (GCNs) have achieved encouraging progress in modeling human body skeletons as spatial-temporal graphs. However, existing methods still suffer from two inherent drawbacks. Firstly, these models process the input data based on the physical structure of the human body, which leads to some latent correlations among joints being ignored. Furthermore, the key temporal relationships between nonadjacent frames are overlooked, preventing to fully learn the changes of the body joints along the temporal dimension. To address these issues, we propose an innovative spatial-temporal model by introducing a self-adaptive GCN (SAGCN) with global attention network, collectively termed SAGGAN. Specifically, the SAGCN module is proposed to construct two additional dynamic topological graphs to learn the common characteristics of all data and represent a unique pattern for each sample, respectively. Meanwhile, the global attention module (spatial attention (SA) and temporal attention (TA) modules) is designed to extract the global connections between different joints in a single frame and model temporal relationships between adjacent and nonadjacent frames in temporal sequences. In this manner, our network can capture richer features of actions for accurate action recognition and overcome the defect of the standard graph convolution. Extensive experiments on three benchmark datasets (NTU-60, NTU-120, and Kinetics) have demonstrated the superiority of our proposed method.

HILPDA-mediated lipidomic remodelling promotes radiotherapy resistance in nasopharyngeal carcinoma by accelerating mitophagy.

Radiotherapy resistance is a major obstacle to nasopharyngeal carcinoma (NPC) therapy and contributes to tumour recurrence and metastasis. Lipid metabolism is a key regulatory mechanism in cancer biology; however, its role in NPC radiotherapy resistance remains unclear. In this study, we identified hypoxia-inducible lipid droplet-associated protein (HILPDA) as a newly discovered regulator of radioresistance that induces not only lipid droplet (LD) formation but also intracellular lipid remodelling, notably changing mitochondrial cardiolipin (CL) levels. Additionally, we found that the upregulation of CL promotes mitophagy in response to irradiation exposure. Mechanistically, HILPDA inhibits PINK1-mediated CLS1 ubiquitination and degradation. The combination of a mitophagy inhibitor and irradiation significantly increases the radiosensitivity of NPC cells. Human cancer-derived data confirmed that the HILPDA-CLS1 pathway promotes NPC radioresistance. Collectively, these findings suggest that HILPDA plays a critical role in promoting NPC radioresistance and might be targeted to overcome radiotherapeutic resistance in NPC patients in the clinic.

Structure-activity relationship and biological evaluation of xanthine derivatives as PCSK9 inhibitors for the treatment of atherosclerosis.

Developing non-statin small molecules for the treatment of hypercholesterolemia remains challenging. The proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapies have attracted considerable attentions. Forty-five 7030B-C5 derivatives were synthesized and evaluated for the PCSK9 repression activity, taking the PCSK9 transcriptional inhibitor 7030B-C5 as the lead. Structure-activity relationship (SAR) analysis at C8 and N7-position was carried out, and compound 3s and 5r exhibited comparable PCSK9 transcriptional inhibitory activity but much lower cytotoxicity with the therapeutic index (TI) values doubled of that of 7030B-C5. In the in vitro assay, both compounds significantly reduced the level of PCSK9 protein and increased LDL receptor (LDLR) protein level. What's more, both compounds promoted LDL cholesterol (LDL-C) clearance more efficiently than 7030B-C5 in HepG2 cells. Most importantly, compound 3s reduced the atherosclerotic plaque areas with promising lipid-lowing effects in ApoE KO mice with a higher in vivo activity and lower toxicity. The regulatory mechanism of 3s was explored that it might target the transcription factor HNF1α and/or HINFP upstream of PCSK9 transcription, similar to that of 7030B-C5. Thus, 3s was considered as a potential anti-atherosclerosis drug candidate as a novel PCSK9 down-regulatory agent, worthy of further investigations.

Bacterial Keratitis Following Small Incision Lenticule Extraction.

Purpose: To describe the development of bacterial keratitis after small incision lenticule extraction in 5 patients and to explore its appropriate therapies. Methods: We retrospectively summarized the clinical treatments of five patients with postoperative bacterial infection after small incision lenticule extraction, who were referred to our hospital from 2019 to 2021. Results: Five male patients had undergone bilateral SMILE in the local hospital due to myopia aged from 18 to 26 years. The onset of keratitis during 1-3 days postoperatively and four of them were severe infection (2 bilateral, 2 unilateral). In five cases, 1 patient (1 eye) who was infected mild keratitis after SMILE was treated with only topical antibiotics; the others who respond poorly to topical antibiotics require surgical treatment, which 1 patient (1 eye) infected necrotic mass of the corneal cap was scraped and irrigated with antibiotic, and 3 patients (5 eyes) were treated by converting the cap to flap, curetting the necrotic tissue and irrigating with the antibiotic solution. In all patients, the duration from onset to resolution was 1-5 weeks. The final uncorrected visual acuity was above 20/32. Conclusion: Owing to the upward popularity of refractive surgery, the incidence of keratitis after SMILE should not be ignored. Early diagnosis and timely treatment of post-SMILE keratitis are essential. For severe keratitis that fails to respond to topical antibiotics, the corneal cap should be opened as a flap.

Arabidopsis RAN GTPases are critical for mitosis during male and female gametogenesis.

The development of male and female gametophytes is a prerequisite for successful propagation of angiosperms. The small GTPases RAN play fundamental roles in numerous cellular processes. Although RAN GTPases have been characterized in plants, their roles in cellular processes are far from understood. We report here that RAN GTPases in Arabidopsis are critical for gametophytic development. RAN1 loss-of-function showed no defects in gametophytic development likely due to redundancy. However, the expression of a dominant negative or constitutively active RAN1 resulted in gametophytic lethality. Genetic interference of RAN GTPases caused the arrest of pollen mitosis I and of mitosis of functional megaspores, implying a key role of properly regulated RAN activity in mitosis during gametophytic development.

Giant Pediatric Supratentorial Tumor: Clinical Feature and Surgical Strategy.

Purpose: To analyze the clinical character of giant pediatric supratentorial tumor (GPST) and explore prognostic factors. Materials and Methods: We analyzed the clinical data comprising of 35 cases of GPST from a single center between January 2015 and December 2020. The tumor volume was measured by 3D slicer software based on preoperative magnetic resonance imaging (MRI). Glasgow Outcome Scale (GOS) was used to evaluate the short-term prognosis. Result: The tumor volume varied from 27.3 to 632.8 ml (mean volume 129.8 ml/ median volume 82.8 ml). Postoperative histopathological types include ependymoma, pilocytic astrocytoma, choroid plexus papilloma (CPP), craniopharyngioma, primitive neuroectoderm tumor (PNET), choroid plexus carcinoma (CPC), immature teratoma, atypical teratoid rhabdoid tumor (AT/RT), anaplastic astrocytoma, and gangliocytoma. Tumors in children younger than 3 years and tumors located at the hemispheres appeared to be larger than their respective counterparts, though no statistical significance was found. A patient with giant immature teratoma died during the operation because of excessive bleeding. Postoperative complications include cerebrospinal fluid subgaleal collection/effusion, infection, neurological deficits, and seizures. The mean GOS score of patients with GPST in 6 months is 3.43 ± 1.12, and 83% of patients (29/35) showed improvement. Favorable GPST characteristics to indicated better GOS included small tumor (≤100 ml) (p = 0.029), low-grade (WHO I-II) (p = 0.001), and gross total resection (GTR) (p = 0.015). WHO grade was highly correlated with GOS score (correlation coefficient = -0.625, p < 0.001). GTR and tumor volume were also correlated (correlation coefficient = -0.428, p = 0.010). Conclusion: The prognosis of GPST is highly correlated with the histopathological type. Smaller tumors are more likely to achieve GTR and might lead to a higher GOS score. Early diagnosis and GTR of the tumor are important for GPST management.

Application Potential of CTHRC1 as a Diagnostic and Prognostic Indicator for Colon Adenocarcinoma.

Colon adenocarcinoma (COAD), ranking third in incidence and second in mortality, is one of the most common cancer types in the world. The initial stages of COAD usually show no obvious clinical symptoms; moreover, effective screening or diagnostic indicators with high sensitivity and specificity are lacking, which often leads to missed treatment opportunities. Collagen triple helix repeat containing 1 (CTHRC1) is a glycosylated protein secreted during tissue repair, which reduces collagen matrix deposition and promotes cell migration. Under physiological conditions, the expression of CTHRC1 is conducive to wound healing; however, the pathological overexpression of CTHRC1 promotes tumour growth and proliferation. In this study, we evaluated the application potential of CTHRC1 as an early diagnosis and prognostic survival monitoring biomarker for COAD in addition to unravelling its molecular mechanism in the development of COAD and exploring new therapeutic targets. Therefore, various tumour databases were used to investigate the expression of CTHRC1 in COAD at the mRNA and protein levels. CTHRC1 expression was found to be significantly increased in COAD, regardless of clinical cancer stage, age, sex or race. Moreover, CTHRC1 expression was significantly correlated with poor prognosis and positively correlated with CD8+ T cell, CD4+ T cell, neutrophil, macrophage and dendritic cell infiltration. The relevant function pathways and neighbouring proteins to CTHRC1 in COAD were identified as ROR2, VAPA, LY6E and several collagen family proteins. Therefore, this study suggests that CTHRC1 is a potential diagnostic and prognostic biomarker for patients with COAD.

Case Report: Whole-Exome Sequencing of Hypothalamic Hamartoma From an Infant With Pallister-Hall Syndrome Revealed Novel de novo Mutation in the GLI3.

Background: GLI-Kruppel family member 3 (GLI3), a zinc finger transcription factor of the sonic hedgehog pathway, is essential for organ development. Mutations in GLI3 cause several congenital conditions, including Pallister-Hall syndrome (PHS), which is characterized by polydactyly and hypothalamic hamartoma. Most patients are diagnosed soon after birth, and surgical removal of hypothalamic hamartoma in the very young is rarely performed because of associated risks. Case presentation: A 7-month-old boy with PHS features, including a suprasellar lesion, bifid epiglottis, tracheal diverticulum, laryngomalacia, left-handed polydactyly and syndactyly, and omental hernia was referred to our service. His suprasellar lesion was partially removed, and whole-exome sequencing was applied to the resected tumor, his peripheral blood, and blood from his parents. Histopathology confirmed the diagnosis of hypothalamic hamartoma, and molecular profiling revealed a likely pathogenic de novo variant, c.2331C>G (p. H777Q), in GLI3. Magnetic resonance imaging follow-up 1 year later showed some residual tumor, and the patient experienced normal development post operation. Conclusions: We presented a case of PHS that carries a novel GLI3 variant. Hypothalamic hamartoma showed a distinct genetic landscape from germline DNA. These data offer insights into the underlying etiology of hypothalamic hamartoma development in patients with PHS.

Influence of global precedence on spatial Stroop effect.

In this study, two experiments were conducted to investigate the influence of global precedence on spatial Stroop effect. Combined stimuli were adopted. In Experiment 1, a Chinese character "" (up) or "" (down) was embedded in an up- or down-pointing arrow; the character was the local feature, whereas the arrow was the global feature. In the spatial task, participants were asked to identify arrow orientation, whereas in the meaning task, they were asked to respond to the character meaning. The results revealed that the RTs were longer for the incongruent trials than for the congruent trials (i.e., spatial Stroop effect) in meaning task, but not in the spatial task. In Experiment 2, an arrow was embedded in a character; the arrow was the local feature, whereas the character was the global feature. The results showed that the effect was found in the spatial task, but not in the meaning task. These results suggest that when combined stimuli are adopted, the spatial Stroop effect is modulated by global precedence. Specifically, the magnitudes of spatial Stroop effect were smaller in the global feature identification than those in the local feature identification.

Dendrobium officinalis inhibited tumor growth in non-small cell lung cancer.

BACKGROUND: Lung cancer is the most common and lethal tumor in the world, and the number of patients who die from lung cancer is growing steadily. Because of conventional chemotherapy drugs' poor tumor selectivity, side effects are significant. Conducting relevant studies and developing highly efficient and low toxicity anti-cancer drugs are urgently needed. Dendrobium officinale, which belongs to Orchidaceae aerophyte, has the characteristic of slow growth and lower natural propagation rate. In China, Dendrobium officinale has a very high value and is often referred to as the "gold of herbs". According to reports in the literature, the active ingredients of Dendrobium officinale have anticancer activity and inhibit neovascularization's potential. This study aimed to investigate the inhibitory effect of Dendrobium officinale in A549 lung cancer cells and its potential involvement in slowing tumor growth. METHODS: We cultured A549 cells and established a cancer xenograft model in nude mice. Infused stomach with Dendrobium officinale was applied to the nude mouse model. Tumor volume and body weight were recorded. RESULTS: The results show that, compared with the negative control group, the gross tumor volume (GTV) of treatment groups decreased (all P<0.05), while the effect of the high concentration of the Dendrobium officinale was more significant than that found in the medium and low group. We believe that Dendrobium officinale exhibits a promising antitumor effect in the nude mouse tumor model. The best treatment concentrations for the nude mouse tumor model were achieved when treatment with the drug began about 7-15 days, and was more significant in high concentrations. CONCLUSIONS: Dendrobium officinale has potent effects of inhibiting tumor on the nude mouse tumor model.

Prognostic value of preoperative hydronephrosis in patients with bladder cancer undergoing radical cystectomy: A meta-analysis.

BACKGROUND: Hydronephrosis is a common finding in patients with bladder cancer. The aim of the study was to appraise the prognostic value of preoperative hydronephrosis in bladder cancer patients undergoing radical cystectomy. METHODS: We conducted a literature search using PubMed and Embase databases in Aug 2018. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effects models. The primary endpoint was overall survival (OS). Secondary endpoints were cancer-specific survival (CSS) and recurrence-free survival (RFS). RESULTS: Overall, 13 studies published between 2008 and 2018 including 4,820 patients were selected for the meta-analysis. The age of bladder cancer patients ranged from 27 to 90.4 years, and the overall proportion of males was 72.5%. Preoperative hydronephrosis was reported in 27.4% of patients. The pooled HR was statistically significant for OS (HR, 1.36; 95% CI [1.20-1.55]) and CSS (HR, 1.64; 95% CI [1.33-2.02]), with no heterogeneity among the enrolled studies. Patients with bilateral hydronephrosis showed a poorer CSS compared to those with no hydronephrosis (HR 5.43, 95% CI [3.14-9.40]). However, there was no difference in CSS between no hydronephrosis and unilateral hydronephrosis groups (HR 1.35, 95% CI [0.84-2.14]). Despite a tendency towards poorer RFS (HR, 1.27; 95% CI [0.96-1.96]), the results demonstrated no significant association between presence of preoperative hydronephrosis and RFS after radical cystectomy. CONCLUSION: This meta-analysis indicates that preoperative hydronephrosis is significantly associated with poorer OS and CSS after radical cystectomy for patients with bladder cancer. Preoperative hydronephrosis has a stronger effect on CSS in patients with bilateral hydronephrosis. The presence of preoperative hydronephrosis not only predicts prognosis, but may also help to identify patients who benefit the most from neoadjuvant chemotherapy.

Development of an Efficient Screening System for HDAC Inhibitor Based on TCF Response Element.

BACKGROUND: Acetylation of core histones is governed by opposing actions of a variety of histone acetyltransferases (HATs) and Histone Deacetylases (HDACs). Deregulation of histone acetylation has been causally linked to cancer development and progression, and can be potentially reversed by drug treatments. HDAC inhibitors (HDACis) have the anti-cancer effects such as induction of cell cycle arrest, promotion of cell apoptosis, and inhibition of metastasis. Many of these HDACis are currently in clinical development. METHODS: To screen for novel compound with HDACis activity, cell-based strategy has been developed in current work. The interaction of HDACs and TCFs was determined by reporter assay, and Natural products library (A10) was screened by our system in colon cancer cells. RESULTS: Based on the interaction of HDACs and TCFs, compounds with HDACis activity could be easily picked out from Natural products library (A10) by using this screening system. Finally, a compound Wsu-18 was preliminarily identified as a potential HDACis. CONCLUSION: These data suggest our screening system for HDACis was efficient and promising, and it is suitable for screening other small molecular chemical libraries.