Showing papers by "Chinese PLA General Hospital published in 2015"

LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b

Abstract: Background Within the last few years, it has become evident that LPS-preconditioned mesenchymal stromal cells (LPS pre-MSCs) show enhanced paracrine effects, including increased trophic support and improved regenerative and repair properties. MSCs may release large amounts of exosomes for cell-to-cell communication and maintain a dynamic and homeostatic microenvironment for tissue repair. The present study assesses the therapeutic efficacy and mechanisms of LPS-preconditioned MSC-derived exosomes (LPS pre-Exo) for chronic inflammation and wound healing.

A Role for Tubular Necroptosis in Cisplatin-Induced AKI

Abstract: Cell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis,atypeofprogrammednecrosis,hasaroleincisplatin-inducedAKI.Wefoundthatinhibitionof any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination ofcytokines(TNF-a,TNF-relatedweakinducerofapoptosis, andIFN-g)thatwereupregulatedinproximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatintreatedmicewaspartiallydiminishedinRIP3-orMLKL-deficientmice,suggestingapositivefeedbackloop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI.

Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, the interventional oncology sans frontières meeting 2013

Abstract: Objectives Previous attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases.

Decreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances.

Abstract: Circular RNA (circRNA) is a type of RNAs which, unlike the better known linear RNA, forms a covalently closed continuous loop. They have emerged recently as a new player in governing fundamental biological processes. However it remains elusive about the correlation of hsa_circ_001988 abundance with colorectal cancer. To investigate the circular RNA expression in colorectal cancer, the targeted hsa_circ_001988 was selected from next generation sequence data base generated in house and then designed divergent primers to amplify hsa_circ_001988 and sequenced it for validation. The expression of hsa_circ_001988 in 31 matched colorectal cancer tissue and normal colon mucosa was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). We used ΔCt method and investigated the differences between tumor tissues and normal colon mucosa by paired t-test. One-way analysis of variance was conducted to analyze the relationship between hsa_circ_001988 expression level and clinic pathological factors of patients. Receiver operating characteristic (ROC) curve was built by SPSS to evaluate the diagnostic values. The expression of hsa_circ_001988 was significantly correlated with differentiation (P<0.05) and perineural invasion (P<0.05). The area under ROC curve of hsa_circ_001988 was 0.788 (P<0.05). Those results indicate that hsa_circ_001988 may become a novel potential biomarker in the diagnosis of colorectal cancer and a potential novel target for the treatment of colorectal cancer.

Brown Adipose Tissue Transplantation Reverses Obesity in Ob/Ob Mice.

Abstract: Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue Accordingly, BAT transplantation increased whole-body thermogenesis Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT

Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis

Abstract: Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis

Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia.

Abstract: The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and the CD3ζ moiety. All enrolled patients had relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-ALL). Of the nine patients, six had definite extramedullary involvement, and the rate of overall survival at 18 weeks was 56%. One of the two patients who received conditioning chemotherapy achieved a three-month durable complete response with partial regression of extramedullary lesions. Four of seven patients who did not receive conditioning chemotherapy achieved dramatic regression or a mixed response in the haematopoietic system and extramedullary tissues for two to nine months. Grade 2-3 graft-versus-host disease (GVHD) was observed in two patients who received substantial donor-derived anti-CD19 CART (chimeric antigen receptor-modified T) cells 3-4 weeks after cell infusions. These results show for the first time that donor-derived anti-CD19 CART cells can cause GVHD and regression of extramedullary B-ALL. This study is registered at www.clinicaltrials.gov as NCT01864889.

Prognostic Value of Procalcitonin in Adult Patients with Sepsis: A Systematic Review and Meta-Analysis

Abstract: Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients However, studies have produced conflicting results The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality We searched PubMed, Embase, Web of Knowledge and the Cochrane Library Articles written in English were included A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients Two authors independently evaluated study eligibility and extracted data The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model We used the Q-test and I2 index to test heterogeneity Twenty-three studies with 3,994 patients were included An elevated PCT level was associated with a higher risk of death The pooled relative risk (RR) was 260 (95% confidence interval (CI), 205–330) using a random-effects model (I2 = 635%) The overall area under the summary receiver operator characteristic (SROC) curve was 077 (95% CI, 073–080), with a sensitivity and specificity of 076 (95% CI, 067–082) and 064 (95% CI, 052–074), respectively There was significant evidence of heterogeneity for the PCT testing time (P = 0020) Initial PCT values were of limited prognostic value in patients with sepsis PCT non-clearance was a prognostic factor of death in patients with sepsis The pooled RR was 305 (95% CI, 235–395) using a fixed-effects model (I2 = 379%) The overall area under the SROC curve was 079 (95% CI, 075–083), with a sensitivity and specificity of 072 (95% CI, 058–082) and 077 (95% CI, 055–090), respectively Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment

B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway.

Abstract: B7-homologue 3 (B7-H3), a recently identified immunoregulatory protein, has been shown to be overexpressed in human hepatocellular carcinoma (HCC). However, whether the dynamic expression pattern of B7-H3 contributes to early invasion of HCC is largely unknown. In addition, the biological roles of B7-H3 in HCC are still unclear. Herein, we are going to examine B7-H3 expression profile and its clinicopathological significance in primary and metastatic HCC, and further determine whether B7-H3 knockdown simulates different pathological states of HCC progression and metastasis. Using immunohistochemistry, B7-H3 expression was studied on 116 HCC containing primary and metastatic HCCs. Survival curves and log-rank tests were used to test the association of B7-H3 expression with survival. HCC cells with B7-H3 depletion were established by RNA interference to investigate the effect of B7-H3 on cell proliferation, apoptosis, migration and invasion in vitro. Statistical analysis of clinical cases revealed that B7-H3 high expression group had inclinations towards late TNM stage, the presence of vascular invasion, lymph metastasis, and the formation of microsatellite tumors. Increased intensity of tumor B7-H3 staining was detected more significantly in metastatic HCC tumors. Consistently in experiments performed in vitro, B7-H3 was able to stimulate the wound healing, metastasis and invasion of hepatoma cells by targeting epithelial-to-mesenchymal transition (EMT) via JAK2/Stat3/Slug signaling pathway, while no obvious influence on cell growth and apoptosis. B7-H3 in the regulation of the metastatic capacity of HCC cells makes itself a promising therapeutic target for anti-metastasis therapy.

In vivo nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging

Abstract: Cerenkov luminescence imaging utilizes visible photons emitted from radiopharmaceuticals to achieve in vivo optical molecular-derived signals. Since Cerenkov radiation is weak, non-optimum for tissue penetration and continuous regardless of biological interactions, it is challenging to detect this signal with a diagnostic dose. Therefore, it is challenging to achieve useful activated optical imaging for the acquisition of direct molecular information. Here we introduce a novel imaging strategy, which converts γ and Cerenkov radiation from radioisotopes into fluorescence through europium oxide nanoparticles. After a series of imaging studies, we demonstrate that this approach provides strong optical signals with high signal-to-background ratios, an ideal tissue penetration spectrum and activatable imaging ability. In comparison with present imaging techniques, it detects tumour lesions with low radioactive tracer uptake or small tumour lesions more effectively. We believe it will facilitate the development of nuclear and optical molecular imaging for new, highly sensitive imaging applications.

Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis

Abstract: // Tengfei Zhang 1,2,* , Ling Cao 1,3,* , Jing Xie 4,* , Ni Shi 5 , Zhen Zhang 1,3 , Zhenzhen Luo 1,3 , Dongli Yue 1,3 , Zimeng Zhang 6 , Liping Wang 3 , Weidong Han 7 , Zhongwei Xu 8 , Hu Chen 9 and Yi Zhang 1,3,10,11 1 Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2 Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States 3 Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 4 Center for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia 5 Comprehensive Cancer Center, the Ohio State University, Columbus, Ohio, United States 6 Department of Immunology, Harvard Medical School, Boston, Massachusetts United States 7 Molecular & Immunological/Bio-Therapeutic Department, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China 8 Department of Gastroenterology, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania, United States 9 Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Science, Beijing, China 10 Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China 11 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China * These authors have contributed equally to this work Correspondence to: Yi Zhang, email: // Keywords : CD19, chimeric antigen receptor, B cell malignancies, meta analysis, efficiency Received : July 06, 2015 Accepted : August 20, 2015 Published : September 10, 2015 Abstract Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed ( p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.

Fibroblast Growth Factors Stimulate Hair Growth through β-Catenin and Shh Expression in C57BL/6 Mice

Abstract: Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.

Aberrant intra- and inter-network connectivity architectures in Alzheimer’s disease and mild cognitive impairment

Abstract: Alzheimer’s disease (AD) patients and those with high-risk mild cognitive impairment are increasingly considered to have dysfunction syndromes. Large-scale network studies based on neuroimaging techniques may provide additional insight into AD pathophysiology. The aim of the present study is to evaluate the impaired network functional connectivity with the disease progression. For this purpose, we explored altered functional connectivities based on previously well-defined brain areas that comprise the five key functional systems [the default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL), sensorimotor network (SMN)] in 35 with AD and 27 with mild cognitive impairment (MCI) subjects, compared with 27 normal cognitive subjects. Based on three levels of analysis, we found that intra- and inter-network connectivity were impaired in AD. Importantly, the interaction between the sensorimotor and attention functions was first attacked at the MCI stage and then extended to the key functional systems in the AD individuals. Lower cognitive ability (lower MMSE scores) was significantly associated with greater reductions in intra- and inter-network connectivity across all patient groups. These profiles indicate that aberrant intra- and inter-network dysfunctions might be potential biomarkers or predictors of AD progression and provide new insight into AD pathophysiology.

Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer.

Abstract: Background: Lung cancer is becoming the leading cause of cancer-related deaths with high mortality worldwide and in China as well. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer accounting for approximately 85% of all cases. Over 70% of cases are at loco-regionally advanced stages or have distant metastasis at the time of presentation with subsequently poor prognosis. MiRNAs are stable molecules in blood and used as biomarkers for the early diagnosis of various malignancy. The purpose of this study was to evaluate whether circulating miR-125a-5p, miR-145 and miR-146a could be used as biomarkers for the diagnosis of NSCLC through measuring their expression and assess their relationship with clinical pathological factors. Methods: Expression levels of serum miR-125a-5p, miR-145 and miR-146a were detected in 70 pairs of NSCLC patients and healthy controls using quantitative real-time PCR analysis. Results: Serum miR-125a-5p, miR-145 and miR-146a were overexpressed in NSCLC patients compared with healthy controls. Their values of the area under the receiver –operating characteristic curve (AUC-ROC) were 0.71, 0.84 and 0.78. Optimal sensitivity and specificity were 73.53% and 55.71%, 92.75% and 61.43%, 84.06% and 58.57%, respectively in differentiating NSCLC patients from healthy controls. Conclusions: These preliminary data suggest that serum miR-125a-5p, miR-145 and miR-146a may be useful noninvasive biomarkers for the clinical diagnosis of NSCLC.

bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway

Abstract: Autophagy is involved in the development and/or progression of many diseases, including myocardial ischemia/reperfusion (I/R). In this study, we hypothesized a protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the myocardial I/R model. Our results showed that bFGF improved heart function recovery and increased the survival of cardiomyocytes in myocardial I/R model. The protective effect of bFGF is related to the inhibition of LC3II levels. Additionally, bFGF enhances the clearance of Ub by p62 and increases the survival of H9C2 cells. Moreover, silencing of p62 partially blocks the clearance of Ub and abolishes the anti-apoptosis effect of bFGF. An shRNA against the autophagic machinery Atg7 increased the survival of H9C2 cells co-treated with bFGF and rapamycin. bFGF activates the downstream signaling of the PI3K/Akt/mTOR pathway. These results indicate that the role of bFGF in myocardial I/R recovery is related to the inhibition of excessive autophagy and increased ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new direction for bFGF drug development for heart disease and identifies protein signaling pathways involved in bFGF action.

Prognostic Significance of Resting Heart Rate and Use of β-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction Findings From the Swedish Heart Failure Registry

Abstract: Background—In heart failure and reduced ejection fraction, the prognostic role of heart rate (HR) in atrial fibrillation (AF) is unknown and the effectiveness of β-blockers has recently been questioned in AF. Methods and Results—A total of 18 858 patients with heart failure and reduced ejection fraction registered with Swedish Heart Failure Registry were included in this study: patients with sinus rhythm (SR; n=11 466) and patients with AF (n=7392). The outcome measure was all-cause mortality. Compared with HR ≤60 beats per minute, the adjusted hazard ratios for mortality in SR were 1.26 for HR=61 to 70 beats per minute, 1.37 for HR=71 to 80 beats per minute, 1.52 for HR=81 to 90 beats per minute, 1.63 for HR=91 to 100 beats per minute, and 2.69 for HR >100 beats per minute. However, in AF, the hazard ratio increased only for HR >100 beats per minute (1.30; P=0.001). β-blocker use was associated with reduced mortality in SR (hazard ratio, 0.77; P=0.011) and in AF (hazard ratio, 0·71; P<0.001). For β-block...

Deferoxamine attenuates lipopolysaccharide-induced neuroinflammation and memory impairment in mice

Abstract: Neuroinflammation often results in enduring cognitive impairment and is a risk factor for postoperative cognitive dysfunction. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that the iron chelator deferoxamine (DFO) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of DFO on the cognitive sequelae of neuroinflammation is unknown. A mouse model of lipopolysaccharide (LPS)-induced cognitive impairment was established to evaluate the neuroprotective effects of DFO against LPS-induced memory deficits and neuroinflammation. Adult C57BL/6 mice were treated with 0.5 μg of DFO 3 days prior to intracerebroventricular microinjection of 2 μg of LPS. Cognitive function was assessed using a Morris water maze from post-injection days 1 to 3. Animal behavioral tests, as well as pathological and biochemical assays were performed to evaluate the LPS-induced hippocampal damage and the neuroprotective effect of DFO. Treatment of mice with LPS resulted in deficits in cognitive performance in the Morris water maze without changing locomotor activity, which were ameliorated by pretreatment with DFO. DFO prevented LPS-induced microglial activation and elevations of IL-1β and TNF-α levels in the hippocampus. Moreover, DFO attenuated elevated expression of caspase-3, modulated GSK3β activity, and prevented LPS-induced increases of MDA and SOD levels in the hippocampus. DFO also significantly blocked LPS-induced iron accumulation and altered expression of proteins related to iron metabolism in the hippocampus. Our results suggest that DFO may possess a neuroprotective effect against LPS-induced neuroinflammation and cognitive deficits via mechanisms involving maintenance of less brain iron, prevention of neuroinflammation, and alleviation of oxidative stress and apoptosis.

Prostatic arterial embolization for the treatment of lower urinary tract symptoms due to large (>80 mL) benign prostatic hyperplasia: results of midterm follow-up from Chinese population

Abstract: Currently, large prostate size (>80 mL) of benign prostatic hyperplasia (BPH) still pose technical challenges for surgical treatment. This prospective study was designed to explore the safety and efficacy of prostatic arterial embolization (PAE) as an alternative treatment for patients with lower urinary tract symptoms (LUTS) due to largeBPH. A total of 117 patients with prostates >80 mL were included in the study; all were failure of medical treatment and unsuited for surgery. PAE was performed using combination of 50-μm and 100-μm particles in size, under local anaesthesia by a unilateral femoral approach. Clinical follow-up was performed using the international prostate symptoms score (IPSS), quality of life (QoL), peak urinary flow (Qmax), post-void residual volume (PVR), international index of erectile function short form (IIEF-5), prostatic specific antigen (PSA) and prostatic volume (PV) measured by magnetic resonance (MR) imaging, at 1, 3, 6 and every 6 months thereafter. The prostatic artery origins in this study population were different from previously published results. PAE was technically successful in 109 of 117 patients (93.2%). Follow-up data were available for the 105 patients with a mean follow-up of 24 months. The clinical improvements in IPSS, QoL, Qmax, PVR, and PV at 1, 3, 6, 12, and 24 months was 94.3%, 94.3%, 93.3%, 92.6%, and 91.7%, respectively. The mean IPSS (pre-PAE vs post-PAE 26.0 vs 9.0; P < .0.01), the mean QoL (5.0 vs 3.0; P < 0.01), the mean Qmax (8.5 vs 14.5; P < 0.01), the mean PVR (125.0 vs 40.0; P < 0.01), and PV (118.0 vs 69.0, with a mean reduction of 41.5%; P < 0.01 ) at 24-month after PAE were significantly different with respect to baseline. The mean IIEF-5 was not statistically different from baseline. No major complications were noted. PAE is a safe and effective treatment method for patients with LUTS due to large volume BPH. PAE may play an important role in patients in whom medical therapy has failed, who are not candidates for open surgery or TURP or refuse any surgical treatment.

MicroRNAs as prognostic molecular signatures in renal cell carcinoma: a systematic review and meta-analysis.

Abstract: This is a systematic review of studies investigating the prognostic value of different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant studies were identified, with a total of 2578 subjects. We found that elevated expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630, and miR-497 was associated with a poor prognosis in RCC patients. Conversely, decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187, miR-129-3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis. We performed meta-analyses on studies to address the prognostic value of miR-21, miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.28-4.08), cancer specific survival (CSS; HR, 4.16; 95% CI, 2.49-6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16-3.98). The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35; 95% CI, 0.15-0.85), OS (HR, 0.45; 95% CI, 0.30-0.69), and DFS (HR 0.30; 95% CI, 0.18-0.50). Our comprehensive systematic review reveals that miRs, especially miR-21 and miR-126, could be promising prognostic markers and useful therapeutic targets in RCC.

Effects of Exendin-4 on bone marrow mesenchymal stem cell proliferation, migration and apoptosis in vitro.

Abstract: Mesenchymal stem cells (MSC) are regarded as an attractive source of therapeutic stem cells for myocardial infarction. However, their limited self-renewal capacity, low migration capacity and poor viability after transplantation hamper the clinical use of MSC; thus, a strategy to enhance the biological functions of MSC is required. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells. However, little information is available regarding the influence of Ex-4 on MSC. In our study, MSC were isolated from bone marrow and cultured in vitro. After treatment with Ex-4, MSC displayed a higher proliferative capacity, increased C-X-C motif receptor 4 (CXCR4) expression and an enhanced migration response. Moreover, in H2O2-induced apoptosis, Ex-4 preserved mitochondrial function through scavenging ROS and balancing the expression of anti- and pro-apoptotic proteins, leading to the inhibition of the mitochondria-dependent cell death pathways and increased cell survival. Moreover, higher phospho-Akt (p-Akt) expression was observed after Ex-4 intervention. However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival. These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications.

Long- and Short-Term Health Effects of Pesticide Exposure: A Cohort Study from China

Abstract: Pesticides are extensively used by farmers in China. However, the effects of pesticides on farmers’ health have not yet been systematically studied. This study evaluated the effects of pesticides exposure on hematological and neurological indicators over 3 years and 10 days respectively. A cohort of 246 farmers was randomly selected from 3 provinces (Guangdong, Jiangxi, and Hebei) in China. Two rounds of health investigations, including blood tests and neurological examinations, were conducted by medical doctors before and after the crop season in 2012. The data on pesticide use in 2009–2011 were collected retrospectively via face-to-face interviews and the 2012 data were collected from personal records maintained by participants prospectively. Ordinary least square (OLS), Probit, and fixed effect models were used to evaluate the relationship between pesticides exposure frequency and the health indicators. Long-term pesticide exposure was found to be associated with increased abnormality of nerve conductions, especially in sensory nerves. It also affected a wide spectrum of health indicators based on blood tests and decreased the tibial nerve compound muscle action potential amplitudes. Short-term health effects included alterations in complete blood count, hepatic and renal functions, and nerve conduction velocities and amplitudes. However, these effects could not be detected after 3 days following pesticide exposure. Overall, our results demonstrate that pesticide exposure adversely affects blood cells, the liver, and the peripheral nervous system. Future studies are needed to elucidate the specific effects of each pesticide and the mechanisms of these effects.

Dynamic changes in amino acid concentration profiles in patients with sepsis.

Abstract: Objectives The goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies. Methods Thirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured. Results The metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively. Conclusions Critically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic. Trial registration ClinicalTrial.gov identifier NCT01818830.