[Effect of Short-Term Exposure to Air Pollutants on Hospital Admissions for End-Stage Renal Disease Patients Undergoing Hemodialysis]. / çŸ­æœŸç©ºæ°”æ±¡æŸ“ç‰©æš´éœ²å¯¹ç»ˆæœ«æœŸè‚¾è„ç— è¡€æ¶²é€æžæ‚£è€ å ¥é™¢æ¬¡æ•°çš„å½±å“.

Objective: To evaluate the association between short-term exposure to air pollutants of end-stage renal disease (ESRD) patients on maintenance hemodialysis and the number of daily hospital admissions. Methods: The data on hospitalizations were obtained from the database of the municipal Urban Employees' Basic Medical Insurance and Urban Residents' Basic Medical Insurance of a city in Southwest China. Single and multiple pollutant generalized additive models were utilized to estimate the effect of air pollutants (CO, NO2, O3, PM10, PM2.5, and SO2) on patient admissions after the lag time of different numbers of days. In addition, subgroup analyses stratified by sex, age, PM2.5 and PM10 concentration thresholds, seasonality, and comorbidity status for cardiovascular diseases and hypertension were conducted. Results: In the single pollutant models, the pollutants significantly associated with patient admissions and the corresponding lag time of the strongest association were as follows, every time CO increased by 0.1 mg/m3, there was a 2.39% increase (95% confidence interval [CI]: 0.96%-3.83%) in patient admissions after 7 days of lag time; every time NO2, O3, PM2.5, PM10, and SO2 increased by 10 µg/m3, patient admissions increased by 4.02% (95% CI: 1.21%-6.91%) after 7 days of lag time, 3.57% (95% CI: 0.78%-6.44%) after 0-4 days of lag time, 2.00% (95% CI: 1.07%-2.93%) after 6 days of lag time, 1.19% (95% CI: 0.51%-1.88%) after 7 days of lag time, and 8.37% (95% CI: 3.08%-13.93%) after 7 days of lag time, respectively. In the multiple pollutant model, every time O3 and PM2.5 increased by 10 µg/m3, there was an increase of 3.18% (95% CI: 0.34%-6.09%) in daily patient admissions after 0-4 days of lag time and an increase of 1.85% (95% CI: 0.44%-3.28%) after 7 days of lag time. Furthermore, subgroup analyses showed that seasonality, the severity of air pollution, and patients' comorbidities might be the effect modifiers for the association between ambient air pollution and hospital admissions in ESRD patients receiving maintenance hemodialysis. Conclusion: Air pollution is closely associated with hospital admissions in ESRD patients undergoing maintenance hemodialysis and the strength of this association varies according to seasonality, the severity of air pollution, and patients' status of comorbidities.

Bayesian Comorbidity Network and Cost Analysis for Asthma.

The evolving disease spectrum poses significant challenges to the asthma management, thus worsening health quality and increased financial burden on patients. However, potential dependency pattern in comorbidity spectrum remains unclear. We built comorbidity networks based on Bayesian networks utilizing 19604 asthma-patient hospitalization data to investigate dependency patterns among asthma comorbidities. We analyze static properties and trajectory behaviors of gender- and age-stratified asthmatic comorbidity networks. Results suggest that chronic obstructive pulmonary disease, respiratory failure, hypertension, atherosclerosis, and gastritis and duodenitis are the hubs of the asthma comorbidity network. They have a strong dependency pattern, while most of the associations among other comorbidities are sparse and weak. The strength of association between comorbidities is higher in female asthmatics than in males. Although the comorbidity network in children with asthma is simple and stable, the onset of common comorbidities as they age will enhance the association between comorbidities and thus increase the risk of developing other comorbidities. Furthermore, the more attributes of comorbidities, the stronger association with each other, and the greater risk of causing high treatment costs. Our study will help to dissect the asthma co-morbidity network and provide a basis for improving asthma management and cost control.

Nanomedicine for urologic cancers: diagnosis and management.

Urologic cancers accounted for more than two million new cases and around 0.8 million deaths in 2020. Although surgery, chemotherapy, and radiotherapy, as well as castration for prostate cancer, remain the cornerstones for managing urologic neoplasms, they can result in severe adverse effects, poor patient compliance, and unsatisfactory survival rates, thus, it is essential to develop novel options that enable the early detection of these malignancies, together with providing accurate diagnoses, and more efficient treatment strategies. Nanomedicine represents an emerging approach that can deliver formulations or drugs across traditional biological barriers in the body and be directed to specific cell types within target organs via active targeting or passive targeting, thus, showing potential to improve the management of urologic cancers. In this review, we discussed the most recent updates on the application of nanomedicines in the diagnosis and treatment of urologic cancers, with focus on prostate, bladder and kidney tumors. We also presented the anti-tumor molecular mechanisms of newly designed nanomedicine for treating urologic cancers, mainly including image-guided surgery, chemotherapy, radiotherapy, gene therapy, immunotherapy, and their synergetic therapy. Current studies have demonstrated the potential advantages of nanomedicine over conventional approaches. However, most developments and new findings in this area have not been validated in clinical trials yet, and therefore, efforts shall be made to translate these research insights into clinical practices for urologic cancers.

CircACTR2 in macrophages promotes renal fibrosis by activating macrophage inflammation and epithelial-mesenchymal transition of renal tubular epithelial cells.

The crosstalk between macrophages and tubular epithelial cells (TECs) actively regulates the progression of renal fibrosis. In the present study, we revealed the significance of circular RNA ACTR2 (circACTR2) in regulating macrophage inflammation, epithelial-mesenchymal transition (EMT) of TECs, and the development of renal fibrosis. Our results showed UUO-induced renal fibrosis was associated with increased inflammation and EMT, hypertrophy of contralateral kidney, up-regulations of circACTR2 and NLRP3, and the down-regulation of miR-561. CircACTR2 sufficiently and essentially promoted the activation of NLRP3 inflammasome, pyroptosis, and inflammation in macrophages, and through paracrine effect, stimulated EMT and fibrosis of TECs. Mechanistically, circACTR2 sponged miR-561 and up-regulated NLRP3 expression level to induce the secretion of IL-1ß. In TECs, IL-1ß induced renal fibrosis via up-regulating fascin-1. Knocking down circACTR2 or elevating miR-561 potently alleviated renal fibrosis in vivo. In summary, circACTR2, by sponging miR-561, activated NLRP3 inflammasome, promoted macrophage inflammation, and stimulated macrophage-induced EMT and fibrosis of TECs. Knocking down circACTR2 and overexpressing miR-561 may, thus, benefit the treatment of renal fibrosis.

Implication of excessive length of stay of asthma patient with heterogenous status attributed to air pollution.

OBJECTIVE: Air pollution has potential risk on asthma patients, further prolongs the length of stay. However, it is unclear that the impact of air pollution on excessive length of stay (ELoS) of heterogeneous asthma patients. In this study, we proposed a K-Nearest Neighbor (KNN) embedded approach incorporating with patient status to analyze the impact of short-term air pollution on the ELoS of asthma patients. METHODS: The KNN embedded approach includes two stages. Firstly, the KNN algorithm was employed to search for the most similar patient community and approximate kernel proxy of each index patient by Euclidean distance. Then, we built the differential fixed-effect linear model to estimate the risk of air pollution to the ELoS. RESULTS: We analyzed 6563 asthma patients' medical insurance records in a large city of China from January to December in 2014. It was found that when the duration of exposure to air pollution (i.e., PM2.5, PM10, SO2, NO2, and CO) reaches around 4-5 days, the risk of increasing the ELoS becomes the largest. But only O3 shows the opposite effect. What's more, CO is the dominant risk to increase the ELoS. With a 1 mg/m3 increment of CO average concentration in 5 days, the ELoS will go up by 0.8157 day (95%CI:0.72,0.9114). Based on the kernel proxy in the top 1% similar patient community, the additional financial burden posed on each patient increases by RMB 488.6002 (95%CI:430.1962,547.0043) due to the ELoS. CONCLUSIONS: The KNN embedded approach is an innovative method that takes into account the heterogeneous patient status, and effectively estimates the impact of air pollution on the ELoS. It is concluded that air pollution poses adverse effects and additional financial burdens on asthma patients. Heterogeneous patients should adopt different strategies in health management to reduce the risk of increasing the ELoS due to air pollution, and improve the efficiency of medical resource utilization. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40201-020-00584-8.

Design Comorbidity Portfolios to Improve Treatment Cost Prediction of Asthma Using Machine Learning.

Comorbidity is an important factor to consider when trying to predict the cost of treating asthma patients. When an asthmatic patient suffered from comorbidity, the cost of treating such a patient becomes dependent on the nature of the comorbidity. Therefore, lack of recognition of comorbidity on asthmatic patient poses a challenge in predicting the cost of treatment. In this study, we proposed a comorbidity portfolio design that improves the prediction cost of treating asthmatic patients by regrouping frequently occurred comorbidities in different cost groups. In the experiment, predictive models, including logistic regression, random forest, support vector machine, classification regression tree, and backpropagation neural network were trained with real-world data of asthmatic patients from 2012 to 2014 in a large city of China. The 10-fold cross validation and random search algorithm were employed to optimize the hyper-parameters. We recorded significant improvements using our model, which are attributed to comorbidity portfolios in area under curve (AUC) and sensitivity increase of 46.89% (standard deviation: 4.45%) and 101.07% (standard deviation: 44.94%), respectively. In risk analysis of comorbidity on cost, respiratory diseases with a cumulative proportion in the adjusted odds ratio of 36.38% (95%CI: 27.61%, 47.86%) and circulatory diseases with a cumulative proportion in the adjusted odds ratio of 23.83% (95%CI: 15.95%, 35.22%) are the dominant risks of asthmatic patients that affects the treatment cost. It is found that the comorbidity portfolio is robust, and provides a better prediction of the high-cost of treating asthmatic patients. The preliminary characterization of the joint risk of multiple comorbidities posed on cost are also reported. This study will be of great help in improving cost prediction and comorbidity management.

Prediction of Proximal Junctional Kyphosis After Posterior Scoliosis Surgery With Machine Learning in the Lenke 5 Adolescent Idiopathic Scoliosis Patient.

OBJECTIVE: To build a model for proximal junctional kyphosis (PJK) prognostication in Lenke 5 adolescent idiopathic scoliosis (AIS) patients undergoing long posterior instrumentation and fusion surgery by machine learning and analyze the risk factors for PJK. MATERIALS AND METHODS: In total, 44 AIS patients (female/male: 34/10; PJK/non-PJK: 34/10) who met the inclusion criteria between January 2013 and December 2018 were retrospectively recruited from West China Hospital. Thirty-seven clinical and radiological features were acquired by two independent investigators. Univariate analyses between PJK and non-PJK groups were carried out. Twelve models were built by using four types of machine learning algorithms in conjunction with two oversampling methods [the synthetic minority technique (SMOTE) and random oversampling]. Area under the receiver operating characteristic curve (AUC) was used for model discrimination, and the clinical utility was evaluated by using F1 score and accuracy. The risk factors were simultaneously analyzed by a Cox regression and machine learning. RESULTS: Statistical differences between PJK and non-PJK groups were as follows: gender (p = 0.001), preoperative factors [thoracic kyphosis (p = 0.03), T1 slope angle (T1S, p = 0.078)], and postoperative factors [T1S (p = 0.097), proximal junctional angle (p = 0.003), upper instrumented vertebra (UIV) - UIV + 1 (p = 0.001)]. Random forest using SMOTE achieved the best prediction performance with AUC = 0.944, accuracy = 0.909, and F1 score = 0.667 on independent testing dataset. Cox model revealed that male gender and larger preoperative T1S were independent prognostic factors of PJK (odds ratio = 10.701 and 57.074, respectively). Gender was also at the first place in the importance ranking of the model with best performance. CONCLUSION: The random forest using SMOTE model has the great value for predicting the individual risk of developing PJK after long instrumentation and fusion surgery in Lenke 5 AIS patients. Moreover, the combination of the outcomes of a Cox model and the feature ranking extracted by machine learning is more valuable than any one alone, especially in the interpretation of risk factors.

MiR-200b/c family inhibits renal fibrosis through modulating epithelial-to-mesenchymal transition via targeting fascin-1/CD44 axis.

BACKGROUND: Renal fibrosis is the characteristic of all kinds of chronic kidney diseases (CKDs). Fascin-1 plays an important role in tumor development, but the roles of fascin-1 in renal fibrosis have not been studied. Here, we explored the role of fascin-1 in renal fibrosis and the potential mechanisms. METHODS: Kidney unilateral ureteral obstruction (UUO) mouse model was used as an in vivo model, and proximal tubule epithelial cell lines treated with TGF-ß1 were used as in vitro model of renal fibrosis. Cell transfection was performed to manipulate the expression of miR-200b/c, fascin-1 and CD44. Western blotting, qRT-PCR, immunohistochemistry or immunofluorescence assays were used to measure levels of miR-200b/c, fascin-1, CD44, and fibrosis and EMT-related markers. H&E and Masson stainings were used to examine the degree of injury and fibrosis in kidneys. Dual luciferase assay was used to examine the interaction between miR-200b/c family and fascin-1. RESULTS: Fascin-1 and CD44 levels were both significantly up-regulated while miR-200b/c family was reduced in models of renal fibrosis. Furthermore, overexpression of miR-200b/c family and inhibition of fascin-1 or CD44 ameliorated renal fibrosis through suppressing EMT process. Mechanistically, miR-200b/c family directly and negatively regulated the expression of fascin-1. Overexpression of fascin-1 could reverse the effects of miR-200b/c family on renal fibrosis, and fascin-1 regulated renal fibrosis by activating CD44. CONCLUSION: Our study is the first to show that fascin-1 plays a critical role in renal fibrosis. MiR-200b/c family could inhibit renal fibrosis through modulating EMT process by directly targeting fascin-1/CD44 axis.

Financial implications of dialysis modalities in the developing world: A Chinese perspective.

BACKGROUND: End-stage renal disease has been imposing a heavy economic burden on public health; however, few studies have been performed on the cost-effectiveness of dialysis modalities. We aim to estimate the cost-effectiveness of different dialysis modalities in China. METHODS: Cost-effectiveness analyses were performed using Markov models based on published data of hemodialysis (HD) and peritoneal dialysis (PD) modalities in China. Sensitivity analyses were conducted to identify key variables influencing the results. RESULTS: Over a 10-year time horizon, the base-case cost-effectiveness analysis indicated that PD-first absolutely dominated the HD-first option by gaining 0.13 more quality-adjusted life years (QALYs) and costing RMB ¥81,081 less. When using reported mortality of HD and PD from the United States, the PD-first option still dominated HD-first with higher QALYs and lower costs. Sensitivity analyses revealed that the results were more sensitive to the direct cost of HD, utility of HD, utility of PD, direct cost of PD, PD mortality, and HD mortality, while less sensitive to the indirect costs and transition probabilities. The HD utility needed to be at least 0.148 higher than PD utility for HD to be cost-effective. PD was about 72% likely to be considered cost-effective compared with HD, regardless of the willingness-to-pay for QALYs. CONCLUSION: PD appears to be more cost-effective than HD in China, and the major influential factors on the cost-effectiveness are the direct costs of HD, utility of HD, utility of PD, direct costs of PD, PD mortality, and HD mortality.

A novel "AIE + ESIPT" near-infrared nanoprobe for the imaging of γ-glutamyl transpeptidase in living cells and the application in precision medicine.

γ-Glutamyl transpeptidase (GGT) has been reported as a biomarker of hepatocellular carcinoma (HCC), and its imaging is of great benefit for early detection in precise medicine as well as intraoperative navigation. Herein, we have designed and synthesized a novel near-infrared fluorescent probe coupled aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) effect for the detection of GGT. Thanks to conjugated glutamate acid, this probe could be dispersed in aqueous solution and showed barely any fluorescence emission. Through a GGT-mediated enzymatic reaction, the aggregation state of the probe in aqueous solution was changed and an intramolecular hydrogen bond was formed, resulting in an enhanced fluorescence emission. An excellent linear relationship was observed and the concentration of GGT measured was in the range of 10-90 U L-1 with a limit of detection calculated at 2.9 U L-1. Its feasibility has been confirmed by detecting GGT in HepG2 cells with high specificity and long-term sustainability, satisfying clinical need. Moreover, this nanoprobe showed great potential for precise medicine guided surgery by realizing fluorescence imaging in human liver tumour tissue and distinguishing it from normal tissue. Thus, we supposed that our AIE coupled ESIPT fluorescent nanoprobe has great potential in the early detection of HCC, the selective fluorescence imaging of GGT positive cells during surgery and application in precision medicine.

Identification of hub genes with diagnostic values in pancreatic cancer by bioinformatics analyses and supervised learning methods.

BACKGROUND: Pancreatic cancer is one of the most lethal tumors with poor prognosis, and lacks of effective biomarkers in diagnosis and treatment. The aim of this investigation was to identify hub genes in pancreatic cancer, which would serve as potential biomarkers for cancer diagnosis and therapy in the future. METHODS: Combination of two expression profiles of GSE16515 and GSE22780 from Gene Expression Omnibus (GEO) database was served as training set. Differentially expressed genes (DEGs) with top 25% variance followed by protein-protein interaction (PPI) network were performed to find candidate genes. Then, hub genes were further screened by survival and cox analyses in The Cancer Genome Atlas (TCGA) database. Finally, hub genes were validated in GSE15471 dataset from GEO by supervised learning methods k-nearest neighbor (kNN) and random forest algorithms. RESULTS: After quality control and batch effect elimination of training set, 181 DEGs bearing top 25% variance were identified as candidate genes. Then, two hub genes, MMP7 and ITGA2, correlating with diagnosis and prognosis of pancreatic cancer were screened as hub genes according to above-mentioned bioinformatics methods. Finally, hub genes were demonstrated to successfully differ tumor samples from normal tissues with predictive accuracies reached to 93.59 and 81.31% by using kNN and random forest algorithms, respectively. CONCLUSIONS: All the hub genes were associated with the regulation of tumor microenvironment, which implicated in tumor proliferation, progression, migration, and metastasis. Our results provide a novel prospect for diagnosis and treatment of pancreatic cancer, which may have a further application in clinical.

Fascin1 promotes gastric cancer progression by facilitatingcell migrationand epithelial-mesenchymal transition.

BACKGROUND: Fascin1 regulates cell motility, migration and invasion. Abnormal fascin1 expression has been implicated in a variety of cancers. In this study, we measured fascin1 expression in gastric cancer tissues from 80 gastric cancer patients, and assessed the correlation of fascin1 expression with a series of clinicopathologic gastric cancer parameters.We also verified the results with 4 gastric cancer cell lines in subsequent in vitro studies. METHODS: We measured mRNA expression of fascin1 with RT-qPCR, and measured protein expressions of fascin1 and EMT markers with western blot in gastric cancer cells. Additionally, we used RT-qPCR to assess fascin1 expression in gastric cancer tissues and adjacent normal tissue.Transwell assay was used for cell migration. Xenograft was established by subcutaneous injection of Fascin1 knockdown gastric cancer cells. RESULTS: Fascin1 expression was greater in gastric cancer cell lines compared to normal cells and the expression increased with decreasing cell differentiation. In addition, fascin1 expression was significantly different between gastric cancer tissue and adjacent normal tissue. Fascin1 positivity was higher in poorly differentiated carcinomas compared to moderately and highly differentiated carcinomas. The fascin1 expression was associated with differentiation, tumor size, lymph node status, distant metastasis and TNM stage, but not patient age and sex. Fascin1 expression in gastric carcinoma cells and tissues is significantly higher than in normal gastric mucosa and adjacent tissue to cancerous tissues, and it increases as cancer cell differentiation decreases. Furthermore, fascin1 expression regulates gastric cancer cell migration, expressions of EMT markers and transcription factors as well as xenograft tumor formation. CONCLUSION: Fascin1 is related with clinicopathologic parameters of gastric cancer and overexpressed both in gastric cell lines and gastric tumor tissue. Knockdown of Fascin1 inhibited gastric cancer cell migration and EMT markers expression.

Effects and mechanisms of action of SARI on androgen-independent prostate cancer (DU145) cells.

This study aimed to characterize the role and mechanisms of action of suppressor of AP-1, regulated by IFN (SARI) in androgen-independent prostate cancer cells using the DU145 cell line. Prostate cancer cell lines were transfected to permit both the overexpression and inhibition of SARI. MTT assays and Transwell assays were performed to detect the effects of SARI overexpression and inhibition on the proliferation activity, invasiveness, and metastatic ability of DU145 cells. Expression of vascular endothelial growth factor (VEGF) and tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was monitored in the experimental groups using a qPCR assay and western blot analysis. Additionally, DU145 cells were separately treated with 5, 50, and 100 µmol/L AG490 for 48 h and SARI expression was detected using the qPCR assay and western blot analysis. We also monitored the effects of AG490 treatment (100 µmol/L for 48 h) on both the SARI-SiRNA DU145 cells and empty vector DU145 (DU145-V) cells using the MTT assay and a Transwell migration assay. SARI overexpression and SARI-SiRNA DU145 prostate cancer cell lines were successfully established. The proliferation activity and the invasion and migration abilities of DU145-SARI cells were significantly lower compared with the DU145-V group (P < 0.05). Conversely, the proliferation activity and the invasion and migration abilities of SARI-SiRNA cells were significantly higher compared with the DU145-V group (P < 0.05). VEGF and p-STAT3 expression levels were lower in the SARI overexpression group compared with the DU145-V group and the control group (P < 0.05). In contrast, VEGF and p-STAT3 expression levels were higher in the SARI-SiRNA group compared with both the DU145-V group and the control group (P < 0.05). In comparison with the control group, SARI expression levels were higher in DU145 cells treated with 50 and 100 µmol/L AG490. Upon treatment with 100 µmol/L AG490 for 48 h, the proliferation activity and invasiveness and migration abilities of SARI-SiRNA cells were significantly higher compared with the DU145-V group (P < 0.05). SARI significantly affects the proliferation, invasion, and metastasis of DU145 cells. It is possible that SARI inhibits the proliferation, invasion, and migration of androgen-independent prostate cancer cells by regulating downstream genes through the SARI/STAT3/VEGF pathways.

Aryne-Mediated [2,3]-Sigmatropic Rearrangement of Tertiary Allylic Amines.

A new strategy has been established for the [2,3]-sigmatropic rearrangement of quaternary allylic ammonium ylides via in situ activation of tertiary allylic amines with arynes under mild conditions. Using 2-(trimethylsilyl)aryl triflates as aryne precursors, a range of tertiary allylic amines bearing electron-withdrawing groups underwent [2,3]-sigmatropic rearrangement to furnish structurally diverse homoallylic amines in moderate to good yields. The reaction enabled construction of quaternary stereocenters with excellent enantiopurity and functionalized cyclopropanes with extremely high diastereoselectivity.

Study of breakthrough cancer pain in an animal model induced by endothelin-1.

Cancer patients with bone metastases often suffer breakthrough pain. However, little progress has been made in the treatment of breakthrough pain and its associated mechanism(s) in the patient with cancer due to lacking of resembling and predictive animal models. We previously have demonstrated that endothelin-1 plays an important role in breakthrough cancer pain. In the present study, we have established an animal model of breakthrough cancer pain induced by endothelin-1. The animal model of breakthrough cancer pain is strictly followed the definition and meets the characteristics of breakthrough pain. The model is reliable, reproducible and easy to be produced. To our knowledge, this is the first report for establishing such an animal model. In addition, we also found that a selective ETA receptor antagonist BQ-123 could reverse endothelin-1 induced breakthrough pain. We further studied the characteristics of pain behaviors such as hind limb use score and voluntary wheel running as well as the electrophysiology of sciatic nerve fibers with the model. The murine model shows high resemblance compared to the breakthrough cancer pain in the patients with cancer clinically. It provides a platform for further study of the pathogenesis of breakthrough cancer pain and targeted intervention.

The Nuclear Molecular Imaging of Protein Brain Receptors in Chronic Pain.

Chronic pain is thought to be a brain disease, but the mechanisms are not well-known. In recent years, brain imaging has become an indispensable tool for pain research. For example, nuclear molecular imaging is a safe and noninvasive technology that allows researchers to probe potential brain regions of interest with suitable biomarkers. These studies help us to understand the central mechanisms of chronic pain states in humans. Brain receptors, such as the opioid receptors, dopamine receptors, NK-1 receptors, 5-HT receptors, NMDA receptors and CGRP receptors, are effector sites of neurotransmission and have prominent roles in pain generation and modulation. With nuclear molecular imaging, density, activity and distribution of such brain receptors can be visualized in vivo. Many PET and SPECT studies have shown that there is a disturbance in the function of these receptors in chronic pain states and other neurologic and/or psychiatric pathologies. Thus, these technologies have the potential to provide us with substantial and useful information of neurochemical and neurocircuit basis for pain. In recent studies, the development of nuclear molecular imaging of these receptors in the brain is summarized.

[Discovery of novel protein biomarkers in early silicosis by proteomics and identification of alpha B-crystallin].

OBJECTIVE: To establish 2-dimensional gel electrophoresis (2-DE) image for the early lung injury rats induced by silica dioxide and to identify differentially expressed protein biomarkers during the early stage of silicosis.
 METHODS: The animal models of silicosis were established and morphology changes were observed by HE staining, and then the key protein biomarkers in silicosis were identified by 2-DE and matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI-TOF-MS) and verified by Western blot.
 RESULTS: The well qualified 2-DE gel images for experimental and control lung tissues were successfully established, and 40 different protein spots was observed when comparing the gel images between the experimental and control groups. Twenty of them were analyzed by MALDI-TOF-MS. A total of 13 altered proteins were identified, including alpha B-crystallin, mast cell protease 6, annexin 1, etc. The expression of alpha B-crystallin in lung was further verified by Western blot.
 CONCLUSION: The protein expression of alpha B-crystallin was increased significantly, suggesting that it might play an important role in the progress of silicosis.

Expression and mechanism of action of the SARI tumor suppressor in prostate cancer.

The objective of this study was to assess the expression of SARI (Suppressor of AP-1, Regulated by IFN) in prostate cancer (Pca) and explore the effects and possible mechanism of action of SARI in the occurrence and development of Pca. In the current study, the expression of SARI was detected using PCR in 40 patients with prostate cancer, 20 patients with prostatic hyperplasia, and prostate cancer cells (LNCaP. and DU145). In addition, the effects of the pro-inflammatory cytokine interferon (IFN)-ß on the expression of SARI in DU145 prostate cancer cells and the possible potential signaling pathways activated by SARI were detected using RT-PCR. The expression of SARI protein was downregulated from 0.6957 ± 0.0104 to 0.1597 ± 0.0032 in prostate cancer cells compared with normal prostate tissues and cells. In addition, SARI gene expression increased from 0.0794 ± 0.0133 to 0.1232 ± 0.0162 significantly in a concentration- and time-dependent manner in DU145 cells treated with IFN-ß (P<0.05). Finally, MTT assays demonstrated that DU145 cells growth slowed down, flow cytometry demonstrated that IFN-ß induced apoptosis increased from 0.0343 ± 0.0039 to 0.0612 + 0.0025 in DU145 prostate cancer cells. In conclusion, the results of the current study suggest that SARI might play an important role in the occurrence and development of prostate cancer. In addition, IFN-ß might inhibit the growth of prostate cancer and promote cellular apoptosis by inducing the expression of SARI.

MicroRNA-145 and MicroRNA-133a Inhibited Proliferation, Migration, and Invasion, While Promoted Apoptosis in Hepatocellular Carcinoma Cells Via Targeting FSCN1.

BACKGROUND: Deregulation of FSCN1 has been observed in human cancers. However, the regulatory mechanism of FSCN1 in hepatocellular carcinoma (HCC) remains largely unknown. AIMS: Our study aimed to reveal the roles of microRNA (miR)-133a, miR-145, and FSCN1 in HCC cells. METHODS: Real-time RT-PCR and western blot were performed to determine the expression of miR-133a, miR-145, and FSCN1. Luciferase reporter assay was used to determine whether FSCN1 was a target of miR-133a and miR-145. Effects of miR-133a, miR-145, and FSCN1 on HCC cell proliferation, apoptosis, migration, and invasion were then investigated. RESULTS: We showed that the expression of FSCN1 was increased in HCC tissues compared to the normal adjacent tissues. Moreover, upregulation of FSCN1 and downregulation of miR-145 and miR-133a co-existed in HCC. Functional studies revealed that miR-145 and miR-133a negatively regulated the expression of FSCN1 in HCC cells, via directly binding to the 3'-untranslational region of FSCN1 mRNA. Overexpression of miR-145 and miR-133a led to decreased FSCN1 expression, and downregulation of miR-145 and miR-133a resulted in increased FSCN1 expression in HCC cells. Furthermore, overexpression of miR-145 and miR-133a inhibited cellular proliferation, migration, and invasion, while promoted apoptosis in HCC cells. On the contrary, inhibition of miR-145 and miR-133a promoted cellular proliferation, migration, and invasion, while suppressed apoptosis in HCC cells. CONCLUSION: Our study suggests that the abnormal upregulation of FSCN1 in HCC is associated with downregulation of miR-145 and miR-133a, and miR-145 and miR-133a inhibit malignant progression of HCC in vitro, possibly via directly targeting FSCN1.

Kinetic resolution of primary allylic amines via palladium-catalyzed asymmetric allylic alkylation of malononitriles.

A range of primary allylic amines were resolved with selectivity factors of up to 491 through [Pd(allyl)Cl]2/(S)-BINAP-catalyzed and mesitylsulfonyl hydrazide-accelerated asymmetric allylic alkylation of malononitriles involving enantioselective C-N bond cleavage under aerobic conditions. Moreover, the reaction proved useful for the asymmetric synthesis of α-branched allyl-substituted malononitriles with high enantiopurity.