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Background: Prostate cancer is a significant clinical issue, particularly for high Gleason score (GS) malignancy patients. Our study aimed to engineer and validate a risk model based on the profiles of high-GS PCa patients for early identification and the prediction of prognosis. Methods: We conducted differential gene expression analysis on patient samples from The Cancer Genome Atlas (TCGA) and enriched our understanding of gene functions. Using the least absolute selection and shrinkage operator (LASSO) regression, we established a risk model and validated it using an independent dataset from the International Cancer Genome Consortium (ICGC). Clinical variables were incorporated into a nomogram to predict overall survival (OS), and machine learning was used to explore the risk factor characteristics’ impact on PCa prognosis. Our prognostic model was confirmed using various databases, including single-cell RNA-sequencing datasets (scRNA-seq), the Cancer Cell Line Encyclopedia (CCLE), PCa cell lines, and tumor tissues. Results: We identified 83 differentially expressed genes (DEGs). Furthermore, WASIR1, KRTAP5-1, TLX1, KIF4A, and IQGAP3 were determined to be significant risk factors for OS and progression-free survival (PFS). Based on these five risk factors, we developed a risk model and nomogram for predicting OS and PFS, with a C-index of 0.823 (95% CI, 0.766–0.881) and a 10-year area under the curve (AUC) value of 0.788 (95% CI, 0.633–0.943). Additionally, the 3-year AUC was 0.759 when validating using ICGC. KRTAP5-1 and WASIR1 were found to be the most influential prognosis factors when using the optimized machine learning model. Finally, the established model was interrelated with immune cell infiltration, and the signals were found to be differentially expressed in PCa cells when using scRNA-seq datasets and tissues. Conclusions: We engineered an original and novel prognostic model based on five gene signatures through TCGA and machine learning, providing new insights into the risk of scarification and survival prediction for PCa patients in clinical practice.

Background and aim: Noninvasive and simple surrogates of right ventricular-arterial coupling (RVAC) have been explored, such as the ratio of tricuspid annular plane systolic excursion / systolic pulmonary artery pressure (TAPSE/sPAP) and systolic volume / end-systolic volume (SV/ESV) deduced from the simplified formula of conductance catheterization. Thus we aimed to investigate the value of three-dimensional echocardiography (3DE) derived SV/ESV in evaluating RVAC of pre-capillary pulmonary hypertension (PH) and compare it with TAPSE/sPAP. We also explored the relationship between SV/ESV with right heart function, hemodynamic index, clinical indicators and prognostic risk stratification. Methods: The study included 59 pre-capillary PH patients who completed right heart catheterization (RHC), cardiac magnetic resonance imaging (CMR) and echocardiography within 7 days. The "gold standard" of RVAC indexes were derived by RHC and CMR data, including Ees/Ea for right ventricular pulmonary artery coupling, Ees for right ventricular end-systolic maximum elasticity and Ea for pulmonary artery effective elasticity. The corresponding 3DE coupling parameters were SV/ESV, 3D Ees and 3D Ea, respectively. Spearman test and Bland-Altman test were used to analyze the correlation and consistency between 3DE coupling parameters with RHC-CMR coupling standard and TAPSE/sPAP; With right ventricular ejection fraction (RV EF)＜35% measured by CMR as the standard diagnostic criterion of uncoupling, the ROC curve was adopted to determine the diagnostic threshold of SV/ESV and TAPSE/sPAP uncoupling. According to SV/ESV diagnostic threshold, patients were divided into coupling and uncoupling group. Independent sample t test and Chi-square test were used to compare the two groups in terms of right heart function, hemodynamic index, clinical indicators and prognostic risk stratification. Results: 3DE coupling parameters (SV/ESV, 3D Ees, 3D Ea) were strongly correlated with RHC-CMR coupling standard (Ees/Ea, Ees and Ea) , respectively (r = 0.880, 0.755, 0.759, P < 0.05). SV/ESV and TAPSE/sPAP were moderately related (r = 0.611, P < 0.05). 3DE coupling parameters and RHC-CMR coupling standard were in good agreement with a low bias, respectively (SV/ESV vs Ees/Ea:-0.053, 3D Ees vs Ees: 0.176 mmHg/mL/m2, 3D Ea vs Ea: 0.393 mmHg/mL/m2) and a satisfactory limits of agreement. The consistency of SV/ESV with TAPSE/sPAP was acceptable (bias: 0.379, 95% CI: -0.006, 0.765). The ROC curve analysis showed the area under the curve (AUC) of TAPSE/sPAP was 0.714 (95% CI, 0.570–0.832）with a optimal cut-off value 0.199 (sensitivity: 70%, specificity: 61.29%). The AUC of SV/ESV was 0.872 (95% CI, 0.759–0.945）with diagnostic threshold 0.533 (sensitivity: 85%, specificity: 74.36%). Right heart echocardiographic parameters (TAPSE, GLS, S’, FAC, RA area, RV/LV, RVOT act), hemodynamic index (mPAP, PVR), clinical indexes (6-minute walking distance, NT-proBNP, WHO FC) and prognostic risk stratification were statistically significant between coupling and uncoupling group (P < 0.05). Conclusion: 3DE derived SV/ESV can reliably evaluate RVAC as a new noninvasive surrogate. SV/ESV less than 0.533 predicted decreased right cardiac function, worsening hemodynamic and clinical status, and higher prognostic risk stratification.

Background According to the new ‘AT(N)’ system, those with a normal amyloid biomarker but with abnormal tauopathy or biomarkers of neurodegeneration or neuronal injury, have been labeled suspected non-Alzheimer’s pathophysiology (SNAP). We aimed to estimate the long-term clinical and cognitive trajectories of SNAP individuals in non-demented elders and its comparison with individual in the Alzheimer’s disease (AD) pathophysiology using ‘AT(N)’ system. Methods We included individuals with available baseline cerebrospinal fluid (CSF) Aβ (A), CSF phosphorylated tau examination (T) and 18F-fluorodeoxyglucose PET or volumetric magnetic resonance imaging (N) from the Alzheimer's Disease Neuroimaging Initiative database. Longitudinal change in clinical outcomes are assessed using linear mixed effects models. Conversion risk from cognitively normal (CN) to cognitively impairment, and conversion from mild cognitive impairment (MCI) to dementia are assessed using multivariate Cox proportional hazard models. Results Totally, 366 SNAP individuals were included (114 A-T-N-, 154 A-T + N-, 54 A-T-N + and 44 A-T + N+) of whom 178 were CN and 188 were MCI. Compared with A-T-N-, CN elders with A-T + N-, A-T-N + and A-T + N + had a faster rate of ADNI-MEM score decline. Moreover, CN older individuals with A-T + N + also had a faster rate of decline in ADNI-MEM score than those with A-T + N- individuals. MCI patients with A-T + N + had a faster rate of ADNI-MEM and ADNI-EF decline and hippocampal volume loss compared with A-T-N- and A-T + N- profiles. CN older individuals with A-T + N + had an increased risk of conversion to cognitive impairment (CDR-GS ≥ 0.5) compared with A-T + N- and A-T-N-. In MCI patients, A-T + N + also had an increased risk of conversion to dementia compared with A-T + N- and A-T-N-. Compared with A-T + N-, CN elders and MCI patients with A + T + N- and A + T + N + had a faster rate of ADNI-MEM score, ADNI-EF score decline, and hippocampal volume loss. CN individuals with A + T + N + had a faster rate of ADNI-EF score decline compare with A-T + N + individuals. Moreover, MCI patients with A + T + N + also had a faster rate of decline in ADNI-MEM score, ADNI-EF score and hippocampal volume loss than those with A-T + N + individuals. Conclusions The findings from clinical, imaging and biomarker studies on SNAP, and its comparison with AD pathophysiology offered an important foundation for future studies.

IntroductionParkinson’s disease is a neurodegenerative disorder involving loss of dopaminergic neurons. Multiple studies implicate the microbiota-gut-brain axis in Parkinson’s disease pathophysiology. Ping-wei-san plus Herbal Decoction, a traditional Chinese medicine composition with beneficial effects in Parkinson’s disease, may have a complex array of actions. Here we sought to determine whether gut microbiota and metabolic pathways are involved in Ping-wei-san plus herbal therapy for Parkinson’s disease and to identify functional pathways to guide research.Methods and resultsThe model of Parkinson’s disease were induced with the rotenone. The Ping-wei-san plus group received the PWP herbal decoction for 90 days, after which all groups were analyzed experimentally. PWP herbal treatment improved motor behavior and emotional performance, balanced gut microbiota, and benefited dietary metabolism. Tandem Mass Tags mass spectrometry identified many differentially expressed proteins (DEPs) in the substantia nigra and duodenum in the PWP group, and these DEPs were enriched in pathways such as those involving cAMP signaling, glutamatergic synapses, dopaminergic synapses, and ribosome-rich functions in the gut. The PWP group showed increases in recombinant tissue inhibitors of metalloproteinase 3, and nucleotide-binding oligomerization domain, leucine rich repeat, and pyrin domain containing proteins 6 in the substantia nigra and decreased parkin, gasdermin D, recombinant tissue inhibitors of metalloproteinase 3, and nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing proteins 6 in the duodenum.DiscussionIn conclusion, this study combined gut microbiota, metabolomics, and proteomics to evaluate the mechanism of action of Ping-wei-san plus on Parkinson’s disease and revealed that PWP herbal treatment modulated gut microbiota, altered metabolite biological pathways, and affected functional pathway protein expression in Parkinson’s disease mice, resulting in therapeutic effects.

Background The standard management for upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). However, some patients cannot undergo this procedure for several reasons, such as unresectable disease, old age, and multiple comorbidities. Our study explored the potential safety and effectiveness of radiotherapy as a curative treatment for UTUC patients unfit for surgery. Methods The data of patients treated with radiotherapy between December 2017 and November 2019 were retrospectively reviewed. For the literature review, computerized PubMed Medline, Index Medicus, and Web of Science databases and reference lists from the identified publications of interest were used. And "upper-tract urothelial carcinoma" and "radiotherapy" were used as key words in the search. Results We describe 8 patients with UTUC who were treated with radiotherapy. The median follow-up time was 13.5 months (range, 8.6-30.9 months). Local tumor control was achieved in all patients. However, distant metastases were observed in 2 patients with T3-4/N+ status. One patient had T4 status and the other had N2+ status. The patients died of tumor progression at 15.0 and 17.7 months. In addition, the other 6 patients who were still alive had relatively early-stage tumors without nodal involvement. Regarding acute toxicity, according to the CTCAE v5.0, mild side effects were noted, including grade 1 nausea and diarrhea. Four patients developed mild anemia, generally of grade 1-2. One patient experienced grade 3 anemia, but it was manageable and improved with symptomatic support. In addition, no grade 4 acute or late toxicities were observed. No significant long-term impairment of renal function occurred. Conclusions For patients with nonmetastatic UTUC who are not suitable for surgery, radiotherapy is a safe treatment and can achieve good local tumor control.

Several echocardiographic methods to estimate pulmonary vascular resistance (PVR) have been proposed. So far, most studies have focused on relatively low PVR in patients with a nonspecific type of pulmonary hypertension. We aimed to clarify the clinical usefulness of a new echocardiographic index for evaluating markedly elevated PVR in chronic thromboembolic pulmonary hypertension (CTEPH). We studied 127 CTEPH patients. We estimated the systolic and mean pulmonary artery pressure using echocardiography (sPAP

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.

The glucagon-like peptide-1 (GLP-1) plays important roles in the regulation of food intake and energy metabolism. Peripheral or central GLP-1 suppresses food intake and reduces body weight. The electrophysiological properties of neurons in the mammalian central nervous system reflect the neuronal excitability and the functional organization of the brain. Recent studies focus on elucidating GLP-1-induced suppression of feeding behaviors and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that activation of GLP-1 receptor (GLP-1R) suppresses food intake and induces postsynaptic depolarization of membrane potential and/or presynaptic modulation of glutamatergic or GABAergic neurotransmission in brain nuclei located within the medulla oblongata, pons, mesencephalon, diencephalon, and telencephalon. This review may provide a background to guide future research about the cellular mechanisms of GLP-1-induced feeding inhibition.

PurposeIt is difficult to contour nerve structures with the naked eye due to poor differentiation between the nerve structures with other soft tissues on CT images. Magnetic resonance neurography (MRN) has the advantage in nerve visualization. The purpose of this study is to identify one MRN sequence to better assist the delineation of the lumbosacral plexus (LSP) nerves to assess the radiation dose to the LSP using the magnetic resonance (MR)/CT deformable coregistration technique.MethodsA total of 18 cases of patients with prostate cancer and one volunteer with radiation-induced lumbosacral plexopathy (RILSP) were enrolled. The data of simulation CT images and original treatment plans were collected. Two MRN sequences (Lr_NerveVIEW sequence and Cs_NerveVIEW sequence) were optimized from a published MRN sequence (3D NerveVIEW sequence). The nerve visualization ability of the Lr_NerveVIEW sequence and the Cs_NerveVIEW sequence was evaluated via a four-point nerve visualization score (NVS) scale in the first 10 patients enrolled to determine the better MRN sequence for assisting nerve contouring. Deformable registration was applied to the selected MRN sequence and simulation CT images to get fused MR/CT images, on which the LSP was delineated. The contouring of the LSP did not alter treatment planning. The dosimetric data of the LSP nerve were collected from the dose–volume histogram in the original treatment plans. The data of the maximal dose (Dmax) and the location of the maximal radiation point received by the LSP structures were collected.ResultsThe Cs_NerveVIEW sequence gained lower NVS scores than the Lr_NerveVIEW sequence (Z=-2.887, p=0.004). The LSP structures were successfully created in 18 patients and one volunteer with MRN (Lr_NerveVIEW)/CT deformable registration techniques, and the LSP structures conformed with the anatomic distribution. In the patient cohort, the percentage of the LSP receiving doses exceeding 50, 55, and 60 Gy was 68% (12/18), 33% (6/18), and 17% (3/18), respectively. For the volunteer with RILSP, the maximum irradiation dose to his LSP nerves was 69 Gy.ConclusionThe Lr_NerveVIEW MRN sequence performed better than the Cs_NerveVIEW sequence in nerve visualization. The dose in the LSP needs to be measured to understand the potential impact on treatment-induced neuropathy.

BackgroundIt is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death.MethodsWe identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan–Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems.ResultsWe analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system.ConclusionsThe NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations.

Background:. The antioxidant effects of bilirubin in Parkinson's disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD. Methods:. Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software. Results:. A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050–0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102–0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: −0.223, 95% CI: −0.952–0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324–0.698, P = 0.000, I2 = 58.0%). Conclusion:. Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.

BACKGROUND: Cardiac flow closely interact with function, however, the correlation of right ventricular (RV) flow and function remains unknown, thus our objective is to observe right ventricular flow with four-dimensional phase-contrast cardiovascular magnetic resonance imaging (4D flow CMR) in patients with pulmonary arterial hypertension (PAH) and to analyze flow components with RV function and hemodynamics. METHODS: This study retrospectively enrolled 30 patients with PAH (mean age: 49±13 years, 16 females) and 14 age- and sex-matched healthy volunteers as controls (mean age: 44±12 years, 9 females). All patients who underwent CMR and right heart catheterization (RHC) within 1 week between January 2019 and July 2020 were included. Hemodynamics were measured with RHC. RV flow components, including the percentages of direct flow (RVPDF), retained inflow (RVPRI), delayed ejection flow (RVPDEF) and residual volume (RVPRVo) were quantified using 4D flow CMR. The associations between RV flow components and other CMR metrics, clinical data, and hemodynamics were analyzed by Spearman’s correlation analysis. RESULTS: In patients with PAH, RVPDF was decreased and RVPRVo was increased compared with the normal control group. The sum of RVPDF and RVPDEF RV was significantly correlated with RV ejection fraction (RVEF) (r=0.802, P

Purpose: Increased volume ratio of Biologic Effective Dose (BED) was associated with higher local control rate in a setting of large (greater than 5 cm) non-small cell lung cancer (NSCLC) via photon partial stereotactic ablative boost radiotherapy (P-SABR). Taking advantage of unique physics characteristic of the Bragg peak, we exploit the potential dosimetric and clinical benefit of using proton P-SABR.Methods: Thirty patients’ CT structure set with large NSCLC previously treated with photon P-SABR were re-planned with three different treatment modalities: intensity modulated proton therapy (Proton-IMPT), proton volumetric modulated arc therapy (Proton-Arc) and photon volumetric modulated arc therapy (Photon-VMAT). Proton-Arc was mimicked with 8 to 14 beams (10 to 20 degree apart). Dosimetric metrics were compared among all of three treatment modalities in which tumor and organ at risks (OARs) doses were compared in volumes receiving >50% and ≤50% of the prescription dose, representing high- and low-dose regions, respectively. Normal Tissue Complication Probability (NTCP) of lungs and esophagus were compared as well.Results: In the high-dose region, mean doses of PTVs were 72.64 GyE, 80.42 GyE and 82.22 GyE and B90 (the ratio of BED>90GyE to the in-field tumor) were 71.17%, 86.59% and 87.32% for Photon-VMAT, Proton-IMPT and Proton-Arc plans, respectively (photon versus proton, p50 of esophageal were comparable for the three treatment modalities (p>0.05). In the low-dose region, doses of OARs were reduced dramatically in proton plans compared with Photon-VMAT plans (pConclusion: Higher BED inside the target could be achieved by using proton beam therapy with similar OARs dose sparing in high-dose region and significantly better OARs low dose sparing compared with photon techniques. Proton techniques has a potential role in the management of large NSCLC to increase the local control rate while reducing the side effect.

The co-contamination discharge of Phthalate esters (PAEs) by human activities and the increased UV radiation is increasing in aquatic ecosystems. However, little information is available about the combined detrimental effects of UV and PAEs on phytoplankton. In this study, the combined effects of UV-B irradiation and di-(2-ethylhexyl) phthalate (DEHP) on photosynthesis and antioxidant system of Scenedesmus acuminatus, and the DEHP degradation were investigated. Results showed that UV-B radiation decreased the chlorophyll a fluorescence yield, photosynthetic activity (Fv/Fm), pigment content and superoxide dismutase activity. This radiation also increased the reactive oxygen species (ROS) production and soluble protein and malondialdehyde contents. UV-B radiation with 10 mg L−1 DEHP improved the Fv/Fm and alleviated the cell damage of S. acuminatus, and the addition of high DEHP concentration (≥50 mg L−1) aggravated cell damage. The ROS generation also decreased with the increased DEHP concentration. UV-B radiation can effectively promote the DEHP degradation, with the highest degradation rate of 89.9% at an initial DEHP concentration of 10 mg L−1 within 6 h. This result may be attributed to that UV-B irradiance induced DEHP degradation under the regulation of ROS generated by S. acuminatus. Our findings will contribute to the understanding of the combined toxic mechanisms of UV-B and DEHP and in the evaluation of ecological environment risks for primary producers in aquatic ecosystems.

Purpose In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells. Patients and methods We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Results We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P 0.05). The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P 0.05). Conclusion Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels.

Xiaobin Gu,1 Xianshu Gao,1 Ming Cui,1 Mu Xie,1 Mingwei Ma,1 Shangbin Qin,1 Xiaoying Li,1 Xin Qi,1 Yun Bai,1 Dian Wang2 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China; 2Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA Objective: This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results: A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7months for RP and EBRT groups, respectively (P20ng/mL were significant risk factors for both CSS and OS. Conclusion: This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged

Yun Bai,1 Xian-shu Gao,1 Shang-bin Qin,1 Jia-yan Chen,1 Meng-meng Su,1 Qing Liu,2 Xiu-bo Qin,2 Ming-wei Ma,1 Bo Zhao,1 Xiao-bin Gu,1 Mu Xie,1 Ming Cui,1 Xin Qi,1 Xiao-ying Li1 1Department of Radiation Oncology, Peking University First Hospital, Beijing, China; 2Department of Medical Imaging, Peking University First Hospital, Beijing, China Purpose: Bulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC. Patients and methods: From December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated. Results: Median follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects .CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P

// Ming Cui 1 , Xian-Shu Gao 1 , Xiaobin Gu 1 , Wei Guo 2 , Xiaoying Li 1 , Mingwei Ma 1 , Shangbin Qin 1 , Xin Qi 1 , Mu Xie 1 , Chuan Peng 1 and Yun Bai 1 1 Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China 2 Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei, China Correspondence to: Xian-Shu Gao, email: doctorgaoxs@126.com Keywords: BRCA2, mutation, prostate cancer, survival, molecular classification Received: January 23, 2017 Accepted: March 21, 2017 Published: March 30, 2017 ABSTRACT The aim of this study was to focus on clinicopathological characteristics and prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 ( BRCA2 ) gene mutation and to offer convincing evidence to consider BRCA2 mutation as a marker of poor prognosis in the molecular classification of PCa. We searched relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library databases to evaluate the differences in the overall survival (OS) and cancer-specific survival (CSS) between BRCA2 mutation carriers and non-carriers in patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers in total from 10 studies in our meta-analysis. The results showed that carrying a BRCA2 mutation was correlated with a reduced CSS and OS when compared with that of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval (CI): 2.10–3.06, P 7), TNM stage (> T3, N1, M1), and risk level than non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor survival outcomes in patients with prostate cancer, especially in those undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.

Importance The prevalence and characteristics of short stature (SS) among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies. Thus far, there have been no accurate estimates of the prevalence of SS in China. Objective To analyze the prevalence of SS among children in China and to explore the influences of sex, area, age, study year, and study site on prevalence rates. Methods Relevant literature was identified by searching the following databases: PubMed, Embase, The Cochrane Library, Chinese Biomedical Literature, China Knowledge Resource Integrated, WeiPu, and WanFang databases. Meta‐analysis was carried out using STATA 11.2. Results This meta‐analysis included 39 studies with 348 326 Chinese participants; the studies covered 20 provinces, municipalities, and autonomous regions. The pooled prevalence of SS was 3.2% (95% confidence interval [CI], 2.6%–3.7%; I 2 = 99.8%). The prevalence of SS in boys and girls were 3.1% (95% CI, 2.5%–3.7%) and 3.2% (95% CI, 2.6%–3.9%), respectively. The sex difference was not statistically significant (P > 0.05). The prevalence of SS was higher in rural areas than in urban areas (4.7% [95% CI, 3.6%–5.8%] vs. 2.8% [95% CI, 2.2%–3.4%]; P < 0.001). The prevalence of SS was higher in West China (5.2%; 95% CI, 4.4%–6.0%) than in Northeast China (0.6%; 95% CI, 0.3%–0.8%), East China (2.3%; 95% CI, 1.9%–2.8%), or Central China (2.9%; 95% CI, 1.9%–3.9%). Interpretation The prevalence of SS among children was higher in western and rural areas of China. Close attention to children’s growth and development is needed to prevent the occurrence of SS.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world. Apart from motor deficits, PD reduces patient’s quality of life through sleep disturbances, cognitive impairment and emotional disorders. However, it’s unclear whether bad life habits such as stay up late exacerbate the patient’s cognition and emotional disorders. Thus we investigated the consequences of sleep deprivation (SD) on memory and emotions using a rotenone-based zebrafish model of PD. Behavioral assays, using locomotor activity assay, showed that rotenone treated zebrafish exhibited PD-like symptoms, whereas sleep deprivation didn’t exacerbate the progression of them. The object discrimination task exhibited that the short-term cognitive deficits of rotenone group are more serious than the sham group after SD. Light-dark box test showed that rotenone treated fish are more dysphoric than the sham fish after SD. Dopamine and DOPAC significantly reduced in rotenone treated fish compared with the sham fish. However, this DOPAC reduction recovered after SD. The expression of D2 and D3 in rotenone treated zebrafish elevated compared with sham group and SD group. However, the rotenone treated zebrafish manifested a decrease level of D2 and D3 after SD. D1 did not show any significantly changes among the four groups. Our findings suggest that zebrafish treated with rotenone may have a more severe damage of memory and emotional function after SD, which may be related to the changes in the DA systems.

Genetic variants of AKT1 have been shown to influence brain function of Parkinson's disease (PD) patients, and in this paper our aim is to investigate the association between the three single-nucleotide polymorphisms (rs2498799; rs2494732; rs1130214) and PD in Han Chinese. 413 Han Chinese PD patients and 450 healthy age and gender-matched controls were genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Both the patient and control groups show similar genotype frequencies at the three loci: rs2498799, rs2494732 and rs1130214. We are able to identify a significant difference in the frequencies of genotype (p=0.019) and G allele (OR=0.764, 95% CI=0.587-0.995, p=0.045) both at rs2498799 between the patient and control groups. Furthermore, the association of subjects with GG genotypes versus those with GA+AA genotype remain significant after adjusting for age in the Han Chinese female cohort (OR=0.538, 95%CI=0.345-0.841, p=0.006), which is especially evident in the late-onset cohort (OR=0.521, 95%CI=0.309-0.877, p=0.012). In contrast, allele frequencies at rs2494732 and rs1130214 were similar between patients and controls in all subgroup analyses. These results suggest that polymorphism of AKT1 locus is associated with risk of PD and that the G allele at rs2498799 may decrease the risk of PD in the North-eastern part of Han Chinese female population.

// Xiaobin Gu 1 , Xian-Shu Gao 1 , Ming Cui 1 , Mu Xie 1 , Chuan Peng 1 , Yun Bai 1 , Wei Guo 2 , Linjun Han 2 , Xiaodong Gu 3 , Wei Xiong 4 1 Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, China 2 Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei, China 3 Department of Breast Cancer Radiotherapy, Tumor Hospital of Shanxi Provence, Taiyuan, China 4 Department of Oncology, Tangshan People’s Hospital, Hebei, China Correspondence to: Xian-Shu Gao, email: doctorgaoxs@126.com Keywords: PLR, gastric cancer, biomarker, prognosis, meta-analysis Received: March 29, 2016 Accepted: June 30, 2016 Published: July 08, 2016 ABSTRACT The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1–1.52, p = 0.001; Ι ² = 68.5%, P h 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC.

Background We performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer. Methods To assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (N = 2071; dCRT = 869 and surgery = 1202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC). Results The 2-year (OR = 1.199, 95% CI 0.922–1.560; P = 0.177) and 5-year overall survival (OS) rates (OR = 0.947, 95% CI 0.628–1.429; P = 0.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (OR = 1.397, 95% CI 0.740–2.638; P = 0.303) or stage II–III (OR = 0.418, 95% CI 0.022–7.833; P = 0.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (OR = 0.226, 95% CI 0.044–1.169; P = 0.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (OR = 1.522, 95% CI 1.035–2.238; P = 0.033). dCRT and surgery led to similar 5-year progression-free survival rates (OR = 1.06, 95% CI 0.79–1.42; P = 0.70). Conclusions dCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC. Electronic supplementary material The online version of this article (10.1186/s12957-018-1470-y) contains supplementary material, which is available to authorized users.

A bialkali photocathode with the quantum efficiency (QE) in the range of a few percent was fabricated for the 704 MHz SRF gun at Brookhaven National Laboratory. The photoemission properties of the bialkali photocathode in the superconducting radio frequency (SRF) gun were measured for the first time, and a good beam experiment result was obtained. The performance of the bialkali photocathode was investigated during the commissioning process of the 704 MHz SRF gun. The effect of electric field on the QE of the cryo-cooled cathode was characterized by an analytical model and a code for the first time.

Copper indium gallium selenide (CIGS) was deposited by metallic precursors sputtering and subsequently submitted to a selenization process. The upper CdS layers were deposited by chemical bath deposition (CBD) technique. The CdS/CIGS interfaces were investigated by Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). As checked by XPS analysis, the CIGS surface exhibited a hydroxide-terminated CdSe layer when treated with Cd Partial Electrolyte solution (Cd PE). Its thickness was roughly estimated to several nanometers. A 100 nm thick CdS layer was deposited onto CIGS surface. The TEM images revealed a clear and sharp interface between CdS and CIGS. XPS analysis showed a CIGS surface covered by a pinhole free and homogeneous CdS layer. XPS depth profile measurement of the CdS/CIGS interface did not evidence elemental inter-diffusion between the CIGS and CdS layers, in very good agreement with TEM observations.

We reported a new method to investigate the phases and structures of thin film bottom parts. The films were polished by flapping papers to reach the bottoms. The surfaces and cross sections of thin films were observed by Scanning Electron Microscopy. Grazing Incidence X-ray Diffraction, Raman spectra and X-ray Photoelectron Spectroscopy (XPS) were used to investigate the phases, structures and chemical components of the surfaces and bottoms of thin films. By this method, we studied the growth processes of chalcopyrite films after the selenization at various temperatures from 270 to 600 °C. At 270 °C, a great amount of Cu–Se nodules formed at the surface, while (In,Ga)–Se stayed in the bottom. At 380 °C, a double layer structure was observed in the film. The top part was typical CuInSe2 polycrystalline, while the bottom part contained complicated components, like CuInSe2, Cu(In,Ga)3Se5, (In,Ga)Se. At 600 °C, a single layer was formed, which was composed of Cu(In,Ga)Se2 phase. However, a higher Ga/(In+Ga) ratio was obtained towards the back contact. In addition, XPS indicated that the Mo/Cu(In,Ga)Se2 interface was rich in Ga and Se.

We report a study of selenization and annealing treatment of copper indium gallium selenide (CIGS) film. Morphologies and composition of surface and cross section were observed by scanning electron microscopy (SEM) equipped with Energy Dispersive Spectroscopy (EDS). X-ray diffraction (XRD) and Raman spectra were used to investigate film structure. Depth profiles of element distributions were detected by Auger electron spectroscopy (AES). A double-layer structure was formed in the film by selenizing metallic precursor at 450 °C. Further annealing at 600 °C in pure argon enhanced gallium diffusion from the bottom to the top of the film, while additional selenium in the annealing had a negative effect. A MoSe 2 layer was detected between CIGS and Mo layers with annealing in additional Se. The annealing treatment also significantly modified the film surface morphology. A large amount of triangular and polygon shaped islands were observed by SEM. That might be due to different nucleation kinetics for different crystal facets.

There are many researches on the correlation between C-reactive protein (CRP) and prognosis of gastric cancer, but whether CRP could be used as an evaluation indicator for prognosis of gastric cancer patients, which was still controversial. Therefore, we conducted meta-analysis based on 18 studies involving 3656 objects. The results show that, CRP was significantly correlated with the risk of poor prognosis of gastric cancer patients [HR (95%CI) 1.50 (1.24, 1.81) P=0.000], and the risk of the poor prognosis can be significantly increased when CRP>10mg/L. In the different clinical stage, high expression of CRP can increases the risk of poor prognosis. The CRP can be used as an important indicator of poor prognosis of gastric cancer patients.

In this work, we report a study of the evolution of Cu–In–Ga–Se system during selenization. The metallic precursors were selenized in Se vapour atmosphere at temperature range from 210 to 380 °C. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman spectra were used to investigate morphological and structural properties of the films. A great amount of thin platelets appeared in the film surfaces at temperature range from 210 to 270 °C. Most platelets had hexagon or polygon structures. The average sizes of these platelets increased with the temperatures. TEM analyses indicated that these platelets had γ-CuSe phases. Beyond 310 °C, most of CuSe platelets decomposed under release of selenium and formed Cu2−xSe. Cu2−xSe might react with InSe for the formation of tetragonal CuInSe2. The average grain sizes increased obviously with the increased temperatures. A possible reaction path to obtain a chalcopyrite structural film was discussed in the end. In addition, Ga was detected rich in the bottom of the film by energy dispersive spectroscopy and grazing incidence X-ray diffraction.

Xiaobin Gu,1 Xian-Shu Gao,1 Wei Xiong,2 Wei Guo,3 Linjun Han,3 Yun Bai,1 Chuan Peng,1 Ming Cui,1 Mu Xie1 1Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China; 2Department of Oncology, Tangshan People’s Hospital, Hebei, People’s Republic of China; 3Graduate School of Medicine, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China Purpose: Accumulating studies have investigated the prognostic and clinical significance of programmed death ligand-1 (PD-L1) expression in patients with hepatocellular carcinoma (HCC); however, the results were conflicting and inconclusive. We conducted a meta-analysis to combine controversial data to precisely evaluate this issue.Methods: Relevant studies were thoroughly searched on PubMed, Web of Science, and Embase until April 2016. Eligible studies were evaluated by selection criteria. Hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the prognostic role of PD-L1 for overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Odds ratio (OR) with 95% CI were selected to assess the relationship between PD-L1 and clinicopathological features of HCC patients. Publication bias was tested using Begg’s funnel plot.Results: A total of seven studies published from 2009 to 2016 were included for meta-analysis. The data showed that high PD-L1 expression was correlated to shorter OS (HR =2.09, 95% CI: 1.66–2.64, P

Background: The vitamin D receptor (VDR) gene has been identified as a candidate gene for susceptibility to Parkinson's disease (PD), but results from genetic association studies to date are inconsistent. Here, we conducted a meta-analysis of published case-control studies to evaluate the association of the extensively studied VDR ApaI (G/T), BsmI (G/A), FokI (C/T), and TaqI (T/C) gene polymorphisms with risk of PD. Methods: Electronic search at PubMed, EMBASE, EBSCO, China National Knowledge Infrastructure, Weipu database, and Wanfang database was conducted to identify all relevant studies. Odds ratio ( OR ) with 95% confidence interval ( CI ) values was applied to evaluate the strength of the association. Results: A total of seven studies with 2034 PD cases and 2432 controls were included in the meta-analysis following the inclusion and exclusion criteria. Overall, no significant association between ApaI, BsmI, and TaqI gene polymorphisms and PD susceptibility in all four genetic models was found (T vs. G: OR = 1.00, 95% CI : 0.89-1.12, P = 0.97; A vs. G: OR = 0.94, 95% CI : 0.77-1.15, P = 0.53; C vs. T: OR = 1.03, 95% CI : 0.85-1.25, P = 0.77) while a significant association between FokI (C/T) and PD risk was observed (C vs. T: OR = 1.41, 95% CI : 1.14-1.75, P = 0.001; CC vs. TT: OR = 2.45, 95% CI : 1.52-3.93, P = 0.0002; CT vs. TT: OR = 2.21, 95% CI : 1.38-3.52, P = 0.0009, CC vs. CT+TT: OR = 2.32, 95% CI : 1.49-3.61, P = 0.0002). Conclusions: Polymorphisms of ApaI, BsmI, and TaqI may not be associated with the susceptibility to PD while the FokI (C/T) polymorphism is possibly associated with increased PD risk. However, conclusions should be cautiously interpreted due to the relatively small number of studies included.

Objective Chronic levodopa (L-dopa) treatment in Parkinson’s disease (PD) is often associated with the development of motor complications, but the corresponding epidemiological data is rare in Chinese PD patients. The present survey was to investigate the prevalence rate of wearing-off (WO) and dyskinesia among the patients with PD in China. Methods From May 2012 to October 2012, a 3-step registry survey for wearing off (WO) and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China. Results There were 1,558 PD patients fulfilling the inclusion criteria. Among them, 1,051 had at least one positive response of 9-item wearing off questionnaire (WOQ-9), 724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists, respectively. The overall prevalence rates of WO and dyskinesia were 46.5% (95% CI 44.0% - 48.9%) and 10.3% (95% CI 8.8% - 11.8%), respectively. The mean score of WOQ-9 for those with WO was 3.8 (SD = 1.8), with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms. Better improvement of motor symptoms (n = 354, 87.8%) and long-term disease control and drug selection (n = 288, 71.5%) were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO. Conclusions This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from mainland China. WO prevalence rate among Chinese PD patients was in line with, while dyskinesia prevalence rate was lower than previous reports from other Countries. Electronic supplementary material The online version of this article (doi:10.1186/2047-9158-3-26) contains supplementary material, which is available to authorized users.

Objective: We investigate the effect of TrkA signaling pathway on the expressions of transient receptor potential channel in 6-hydroxydopamine(6-OHDA) lesioned rat treated by electroacupuncture and to explore the role of trkA signaling pathway and TRP subfamily in the pathogenesis of Parkinson's disease (PD), which would reveals the mechanisms of electroacupuncture (EA) neuroprotective effect. Methods: The experimental models were established by unilateral injection of 6-OHDA into the left medial forebrain bundle (MFB).TrkA signaling pathway inhibitor K252a was infected into MFB through two small burr holes in the skull to block trkA signal.The change of TRPC1 and TRPC3 expressions was detected by use of immunohistochemistry and RT-PCR as well as TUNEL for cell apoptosis. Results: The expressions of TRPC1 and TRPC3 in the substantia nigra (SN) of the 6-OHDA lesioned rat were significantly reduced. Compared with PD model group, TRPC1 and TRPC3 expressions were significantly increased in the EA group. There was no statistically significance in TRPC1 and TRPC3 expressions between K252a and PD model groups (P> 0.05). The number of apoptotic cells in SN increased 54.5% in the PD model rats, while positive apoptotic cells were significantly reduced in the EA group. There was no statistically significance in apoptotic cells between K252a and PD model groups (P>0.05). Conclusion: TRPC1 and TRPC3 expressions downregulated in the SN of the 6-OHDA lesioned rat, which was accompanied by apoptosis increase in the SN. EA treatment could reverse this effect, and trkA signaling pathway inhibitors K252a can attenuate the neuroprotective effect of EA. It suggested that TRPC1 and TRPC3 may play an important role in the pathogenesis of PD, and certain TRPC subfamily expressions change may be associated with the pathogenesis of PD. Its expression might be subject to trkA signaling pathway, and this signal pathway may be the regulation target for EA neuroprotection.