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Cell senescence, glycolysis, and mitochondrial deficit jointly regulate the development of septic acute kidney injury (SAKI). This study aimed to explore the role of circular RNA HIPK3 (circHIPK3) in mitochondrial function in SAKI. The SAKI mouse model was established by Candida albicans infection, followed by Western blot assay, measurements of serum lactate, and adenosine triphosphate (ATP), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) staining and flow cytometry. Human renal tubular epithelial cells were treated with lipopolysaccharide to establish the SAKI cell model, followed by cell counting kit-8 assay, tests of hexokinase activity, lactate production, oxygen consumption rate, extracellular acidification rate, ATP, and JC-1 staining, and Western blot assay. The roles of mitochondrial pyruvate carrier 1 (MPC1) were validated by kidney function tests, hematoxylin and eosin staining, periodic acid-Schiff staining, and SA-β-gal staining. circHIPK3 downregulation reduced glycolysis and mitochondrial dysfunction both in vivo and in vitro through the microRNA (miR)-148b-3p/DNMT1/3a/Klotho axis. Inhibition of miR-148b-3p or Klotho increased glycolysis and mitochondrial dysfunction. Knockdown of MPC1 increased lactate content and decreased ATP levels and MMP both in vivo and in vitro. Collectively, circHIPK3, in concert with the miR-148b-3p/DNMT1/3a/Klotho axis, increased glycolysis, and inhibited the negative regulation of lactate production by MPC1, and aggravated mitochondrial dysfunction and cell senescence in SAKI., (© 2024 Wiley Periodicals LLC.)

Neural radiance fields (NeRFs) leverage a neural representation to encode scenes, obtaining photorealistic rendering of novel views. However, NeRF has notable limitations. A significant drawback is that it does not capture surface geometry and only renders the object surface colors. Furthermore, the training of NeRF is exceedingly time-consuming. We propose Depth-NeRF as a solution to these issues. Specifically, our approach employs a fast depth completion algorithm to denoise and complete the depth maps generated by RGB-D cameras. These improved depth maps guide the sampling points of NeRF to be distributed closer to the scene's surface, benefiting from dense depth information. Furthermore, we have optimized the network structure of NeRF and integrated depth information to constrain the optimization process, ensuring that the termination distribution of the ray is consistent with the scene's geometry. Compared to NeRF, our method accelerates the training speed by 18%, and the rendered images achieve a higher PSNR than those obtained by mainstream methods. Additionally, there is a significant reduction in RMSE between the rendered scene depth and the ground truth depth, which indicates that our method can better capture the geometric information of the scene. With these improvements, we can train the NeRF model more efficiently and achieve more accurate rendering results.

Purpose: The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown., Methods and Materials: In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed., Results: Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P = .06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P = .067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P = .028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P = .037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P = .076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P = .038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P = .041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ = -0.45; P = .02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ = -0.56; P = .003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ = 0.40; P = .05) in posttreatment samples., Conclusions: nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The machine learning models with dose factors and the deep learning models with dose distribution matrix have been used to building lung toxics models for radiotherapy and achieve promising results. However, few studies have integrated clinical features into deep learning models. This study aimed to explore the role of three-dimension dose distribution and clinical features in predicting radiation pneumonitis (RP) in esophageal cancer patients after radiotherapy and designed a new hybrid deep learning network to predict the incidence of RP., Methods: A total of 105 esophageal cancer patients previously treated with radiotherapy were enrolled in this study. The three-dimension (3D) dose distributions within the lung were extracted from the treatment planning system, converted into 3D matrixes and used as inputs to predict RP with ResNet. In total, 15 clinical factors were normalized and converted into one-dimension (1D) matrixes. A new prediction model (HybridNet) was then built based on a hybrid deep learning network, which combined 3D ResNet18 and 1D convolution layers. Machine learning-based prediction models, which use the traditional dosiomic factors with and without the clinical factors as inputs, were also constructed and their predictive performance compared with that of HybridNet using tenfold cross validation. Accuracy and area under the receiver operator characteristic curve (AUC) were used to evaluate the model effect. DeLong test was used to compare the prediction results of the models., Results: The deep learning-based model achieved superior prediction results compared with machine learning-based models. ResNet performed best in the group that only considered dose factors (accuracy, 0.78 ± 0.05; AUC, 0.82 ± 0.25), whereas HybridNet performed best in the group that considered both dose factors and clinical factors (accuracy, 0.85 ± 0.13; AUC, 0.91 ± 0.09). HybridNet had higher accuracy than that of Resnet (p = 0.009)., Conclusion: Based on prediction results, the proposed HybridNet model could predict RP in esophageal cancer patients after radiotherapy with significantly higher accuracy, suggesting its potential as a useful tool for clinical decision-making. This study demonstrated that the information in dose distribution is worth further exploration, and combining multiple types of features contributes to predict radiotherapy response., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: This prospective study investigated the incidence of radiation pneumonitis (RP) after immunotherapy followed by radiotherapy in non-small-cell lung cancer, analyzed the risk factors for RP, and explored the predictive performance of dosimetry and dosiomics. Methods & materials: Risk factors for grade ≥2 RP were calculated by using a logistic regression model. Predictive performance was compared on the basis of area under the curve values. Results: Grade ≥2 RP occurred in 16 cases (26.7%). The AUC values of V 5 Gy , gray-level dependence matrix-small dependence high gray-level emphasis (GLDM-SDHGLE) and combined features were 0.685, 0.724 and 0.734, respectively. Conclusion: Smoking history, bilateral lung V 5 Gy  and GLDM-SDHGLE were independent risk factors for RP. Dosiomics can effectively predict RP.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Circular RNAs (circRNAs) have been widely reported to play a role in the pathogenesis of various tumors. Nevertheless, the function of circ_0001955 in NSCLC progression has not been explored yet. This study aims to explore the functions of circ_0001955 in NSCLC and investigate its regulatory molecular mechanism. First, we determined that circ_0001955 was upregulated in NSCLC cells. Subsequently, we demonstrated that knockdown of circ_0001955 restrained cell proliferation and invasion. In vivo experiments further proved the suppressive effect of circ_0001955 silence on tumor growth. Mechanism assays revealed that circ_0001955 enhanced nuclear factor-κB (NF-κB) inhibitor interacting Ras-like protein 2 (NKIRAS2) expression by sponging microRNA-29a-3p (miR-29a-3p). Upregulation of NKIRAS2 led to the deceased level of IκBβ but increased levels of nuclear p65, thus activating the NF-κB signaling pathway. In conclusion, Circ_0001955 activates the NF-κB pathway to promote NSCLC cell proliferation and invasion by regulating miR-29a-3p/NKIRAS2 axis., (© 2023 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Our aim was to investigate the predictive value of microRNA (miR)-411-5p and computed tomography perfusion (CTP) parameters on the prognosis of acute cerebral infarction (ACI) patients receiving intravenous thrombolysis based on analyzing the expression changes of miR-411-5p before and after thrombolytic therapy., Methods: Serum miR-411-5p expression in 96 patients with ACI was measured using quantitative real-time PCR. To evaluate prognosis, we measured National Institutes of Health Stroke Scale (NIHSS) scores before and 24 h after thrombolytic therapy in ACI patients and the modified Rankin scale (mRS) score at 3 months (90 days) after ACI onset. Influence factors analysis to predict the prognosis of patients who received thrombolytic therapy was performed by logistic regression analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy and thresholds of factors associated with thrombolytic prognosis., Results: Serum miR-411-5p at 24 h after thrombolysis and at 3 months after onset in ACI patients was upregulated. Additionally, the correlation of miR-411-5p with NIHSS score and CTP parameters were found. Moreover, miR-411-5p and two CTP parameters [cerebral blood flow (CBF) and cerebral blood volume (CBV)] were identified as independent predictors of short- and long-term prognosis following thrombolysis in ACI patients. Furthermore, miR-411-5p, CBF and CBV had high predictive accuracy for patient prognosis, and their combination had the best accuracy., Conclusion: miR-411-5p is increased by thrombolytic therapy in ACI patients, and miR-411-5p, CBF and CBV may serve as independent biomarkers for predicting short- and long-term prognosis following intravenous thrombolysis in ACI patients., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)

Trees growing on paved lands endure many environmental stresses in the urban environment. However, the morphological and physiological mechanisms underlying tree adaptation to pavement in the field are less known. In this study, we investigated 40 sites where Ginkgo biloba and Platanus orientalis grow on adjacent pairs of paved and vegetated plots in parks and roadsides in Beijing, China. Relative to the vegetated land, the mean increments in the diameter at breast height and height in the paved land were significantly decreased by 44.5% and 31.9% for G. biloba and 31.7% and 60.1% for P. orientalis , respectively. These decreases are related to both the decrease in assimilation products due to the reductions in leaf area, leaf total nitrogen content, and chlorophyll content and the increase in energy cost due to the synthesis of more soluble sugar and proline for mitigating stress. The increase in leaf soluble sugar content, proline content, and δ 13 C indicated that trees could adapt to the paved land through the regulation of osmotic balance and the enhancement of water-use efficiency. Piecewise structural equation models showed that trees growing on the paved land are stressed by compounding impacts of the leaf morphological and physiological changes. Therefore, it is critical to explore the complex response of plant morphological and physiological traits to the pavement-induced stress for improving tree health in urban greening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with the authors BC, CG, DZ, ZO and XW at the time of the review., (Copyright © 2022 Cui, Wang, Su, Gong, Zhang, Ouyang and Wang.)

Thyroid dysfunction (TD) induced by programmed death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely reported. However, the effects of ICI-induced TD on the survival of patients with esophageal squamous cell carcinoma (ESCC) have not been described. Herein, a retrospective study was conducted, which 82 patients with advanced metastatic or recurrent ESCC treated with camrelizumab were enrolled. Twenty patients (24.4%) experienced TD during camrelizumab treatment with or without chemotherapy. The median onset time of TD was 1.7 months. The incidence of TD was 35.6% in patients who previously received thoracic radiotherapy versus 10.8% in patients who did not (P =0.009). Patients with TD had significantly longer median progression-free survival (5.5 months vs 3.5 months, P =0.035) and overall survival (26.7 months vs 11.5 months, P <0.001). TD is frequently observed in ESCC patients treated with camrelizumab and especially in patients who received radiotherapy previously. ESCC patients with TD during ICIs treatment often have better prognosis., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Ying Chen et al.)

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. Some microRNAs (miRNAs) play critical roles in the development of many neurological diseases. This study aims to evaluate the clinical significance and biological function of miR-485-3p in the development and progression of PD. The expression of miR-485-3p in serum of PD patients was analyzed by quantitative real-time PCR (qRT-PCR). LPS-treated microglia BV2 cells were used to mimic neuroinflammation in the pathogenesis of PD. The levels of inflammatory cytokines, including IL-1β, IL-6 and TNF-α, were detected by enzyme-linked immunosorbent assay (ELISA). The diagnosis value of miR-485-3p was evaluated by plotting receiver operating characteristic (ROC) curves. A luciferase reporter assay was performed to demonstrate the interaction between miR-485-3p and FBXO45. The results showed that miR-485-3p was significantly up-regulated in serum of PD patients compared with that in both Alzheimer's disease (AD) and healthy cases, and had diagnostic accuracy for PD screening. The activated microglia BV2 cells induced by LPS also had elevated miR-485-3p, and the knockdown of miR-485-3p inhibited the release of pro-inflammatory cytokines. FBXO protein 45 (FBXO45) served as a potential target of miR-485-3p, which was speculated to mediate the function of miR-485-3p. Our results suggest that the up-regulated expression of miR-485-3p in PD may be a novel diagnostic biomarker for PD. Reducing the expression level of miR-485-3p can inhibit the inflammatory responses of BV2 cells, which indicated that miR-485-3p, as a regulator of neuroinflammation, may have the potential as a therapeutic target in PD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lung squamous cell carcinoma (LUSC) is a prevalent subtype of nonsmall cell lung cancer (NSCLC). Dysregulated long noncoding RNAs (lncRNAs) are increasingly identified as pivotal modulators in cancer progression. NCK1 divergent transcript (NCK1-AS1) is a lncRNA that has been proven to be oncogenic in different types of human cancers. However, whether it exerts similar functions in LUSC remains to be elusive. The present study focused on investigating the influence of NCK1-AS1 on the cellular process in LUSC and exploring its underlying mechanism. Through online bioinformatics analysis, we obtained a high NCK1-AS1 level in LUSC tissues. Meanwhile, we confirmed that NCK1-AS1 was upregulated in LUSC cells. Gain- or loss-of-function assays suggested that NCK1-AS1 prompted cell proliferation and migration, whilst impeded cell apoptosis in LUSC. Mechanistically, we revealed that NCK1-AS1 induced the upregulation of its nearby gene NCK adaptor protein 1 (NCK1) at the transcriptional level by interacting with the transcription factor MYC proto-oncogene (MYC). Rescue assays indicated that NCK1 participated in the regulation of NCK1-AS1 on LUSC progression. In conclusion, we firstly demonstrated the oncogenic role of NCK1-AS1 in LUSC and illustrated its downstream molecular mechanism.

Purpose: Radiation dose used in the neoadjuvant chemoradiotherapy (NCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) varies in different trials and clinical practice. Methods and Materials: Data from patients diagnosed with ESCC receiving NCRT followed by esophagectomy were retrospectively collected from February 2013 to December 2017. Lower dose (LD) radiotherapy was defined as ≤45 Gy, and >45 Gy was considered as higher dose (HD). Survival rates were calculated by the Kaplan-Meier method and compared with long-rank test. Multivariate Cox regression analyses were performed to identify variables associated with survival. Results: A total of 118 patients treated with NCRT were included in our analysis: 62 patients received LD radiotherapy, and 56 patients received HD radiotherapy. The median follow-up time was 24.3 months (0.67-65.3 m). Two-years overall survival (OS) rates were 75.0 and 79.0% in HD and LD group, respectively ( P = 0.360), and complete pathological remission (pCR) rates in two groups were 42.9 and 30.6%, respectively ( P = 0.17). The incidences of toxic effects including post-operative complications were not significantly different between two groups. Multivariate analysis showed that tumor T stage, M1a disease, smoking history, and pCR rate were significantly associated with OS. Conclusions: In ESCC patients treated with NCRT followed by surgery, higher radiation dose was not significantly associated with a higher pCR rate and longer survival. Lower radiation dose might be a preferable time-dose fraction scheme. Our finding needs to be further validated by randomized trials., (Copyright © 2020 Yang, Xu, Zhou, Bao, Zhang, Gu, Du, Chen and Qiu.)

The purpose of the present study was to study the effects of resveratrol on cognitive function in rats with vascular dementia and to investigate the molecular mechanisms of its neuroprotective effects. Forty‑five SD rats were randomly divided into 3 groups: The control group (Con group, n=15), the model group (VD group, n=15) and the resveratrol‑treated VD group (Res group, n=15). The VD rats (the VD group and the Res group) were generated by bilateral common carotid artery occlusion. The rats in the Res group received daily resveratrol treatment intraperitoneally for 4 weeks. Cognitive function was tested using the Morris water maze test. The levels of SOD and MDA (oxidative stress indicators) were detected by ELISA kits. The protein expression of Bax, Bcl‑2 and caspase‑3 was detected by western blotting. Compared with the rats in the Con group, the rats in the VD group exhibited decreased cognitive function, significantly increased hippocampal content of MDA, Bax and caspase‑3 (P<0.05), and significantly reduced hippocampal expression of SOD and Bcl‑2 (P<0.05). Compared with the rats in the VD group, the rats in the Res group exhibited increased cognitive ability, reduced hippocampal content of MDA, Bax and caspase‑3 (P<0.05), and increased hippocampal expression of SOD and Bcl‑2 (P<0.05). Resveratrol treatment significantly improved the spatial learning and memory of the VD rats. The mechanism associated with the neuroprotective effects of resveratrol may be closely related to the inhibition of the apoptosis pathway and oxidative stress injury.

Background: Primary familial brain calcification (PFBC) is a rare calcifying disorder of the brain with extensive clinical and genetic heterogeneity. Its prevalence is underestimated due to clinical selection bias (compared with symptomatic PFBC patients, asymptomatic ones are less likely to undergo genetic testing)., Methods: A total of 273 PFBC probands were enrolled in a multicenter retrospective cohort study by two different approaches. In Group I (nonsystematic approach), 37 probands diagnosed at our clinic were enrolled. In Group II (systematic approach), 236 probands were enrolled by searching the medical imaging databases of 50 other hospitals using specific keywords. Genetic testing of four genes known to be causative of autosomal dominant PFBC was performed in all probands using cDNA. All identified variants were further confirmed using genomic DNA and classified according to ACMG-AMP recommendations., Results: Thirty-two variants including 22 novel variants were detected in 37 probands. Among these probands, 83.8% (31/37) were asymptomatic. Two probands with homozygous pathogenic SLC20A2 variants presented more severe brain calcification and symptoms. Based on the variant detection rate of probands in Group II, we extrapolated an overall minimal prevalence of PFBC of 6.6 per 1,000, much higher than previously reported (2.1 per 1000)., Conclusions: We identified a higher proportion of genetically confirmed PFBC probands who were asymptomatic. These patients would be overlooked due to clinical selection bias, leading to underestimation of the disease prevalence. Considering that PFBC patients with biallelic variants had more severe phenotypes, this specific condition should be focused on in genetic counseling., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To explore the effect of lean management on cost control of single disease in patients with acute cerebral infarction (ACI) in stroke center., Methods: A retrospective study was conducted. The patients with ACI who underwent intravenous thrombolysis in the stroke center of Taizhou Central Hospital in Zhejiang Province were enrolled. Thirty patients adopted traditional management procedures from July 2016 to September 2017 were enrolled in the control group, and 32 patients received lean management from October 2017 to December 2018 were enrolled in the lean group. The patients in the control group were treated with traditional intravenous thrombolysis, and the patients were sent to the neurology ward for intravenous thrombolysis. The patients in the lean group applied lean management value stream to optimize process management, the lean management team of the stroke center was established, and the green channel for stroke treatment was established to eliminate the waiting time as far as possible. The location of thrombolysis was changed from neurology ward to the neurological intensive care unit (NICU) in emergency department. The patients in the two groups were compared in terms of intravenous thrombolytic door-to-needle time (DNT), admission time to the neurologist's visit time (T1), CT examination time to neurology ward or NICU admission time (T2), neurology ward/NICU visit time to medication time (T3), and the proportion of patients with DNT controlled within 40 minutes, recovery of neurological impairment 7 days after thrombolysis [national institutes of health stroke scale (NIHSS) score], activity of daily living assessment (Barthel index), length of hospital stay, cost of hospital stay and patient satisfaction. At the same time, the main process quality and the implementation rate of easily missed indexes of cerebral infarction single disease were recorded., Results: Compared with the control group, DNT, T1 and T2 in the lean group were significantly shortened [DNT (minutes): 39.56±11.12 vs. 63.03±19.63, T1 (minutes): 16.23±6.79 vs. 33.48±12.63, T2 (minutes): 13.45±3.84 vs. 17.47±5.56, all P < 0.01], T3 was slightly shortened (minutes: 9.88±1.95 vs. 10.95±2.69, P > 0.05), and the proportion of DNT control within 40 minutes was significantly increased [75.0% (24/32) vs. 16.7% (5/30), P < 0.01], the 7-day NIHSS score was decreased significantly (8.66±4.12 vs. 13.00±5.63, P < 0.01), 7-day Barthel index was increased significantly (71.6±16.7 vs. 54.7±17.1, P < 0.01), the length of hospital stay was significantly shortened (days: 9.69±4.06 vs. 12.47±3.83, P < 0.01), the hospital costs were significantly reduced (Yuan: 16 338±5 481 vs. 19 470±5 495, P < 0.05), the satisfaction of patients was improved significantly [(91.38±2.69)% vs. (86.53±2.78)%, P < 0.01]. In terms of the implementation rate of quality indicators such as pre-application evaluation of thrombolytic drugs, evaluation of dysphagia, and evaluation of vascular function, health education of ACI, rehabilitation evaluation and implementation within 24 hours, etc., the lean group was significantly improved as compared with the control group [(87.5% (28/32) vs. 53.3% (16/30), 96.9% (31/32) vs. 73.3% (22/30), 78.1% (25/32) vs. 43.3% (13/30), 100.0% (32/32) vs. 76.7% (23/30), 75.0% (24/32) vs. 33.3% (10/30), all P < 0.05]., Conclusions: Lean thinking can realize the standardization of stroke center process, effectively utilize medical resources, improve medical quality and reduce the cost of cerebral infarction single disease.

Objective: To investigate the effect of intermittent high glucose on oxygen-glucose deprivation/refurnish (OGD/R) neuronal survival., Methods: The primary cultured hippocampal neurons of mice were sub-cultured when the cell fusion reached about 80%. Cells in logarithmic growth phase were placed in a hypoxic incubator (37 centigrade, 5% CO 2 , 95% N 2 ) to simulate cell hypoxia. The culture medium was replaced by glucose-free Hank equilibrium salt solution (HBSS) to simulate cell hypoglycemia. The normal glucose and oxygen control group was set up. Cell morphology was observed under inverted phase contrast microscope after 6 hours of hypoxia and hypoglycemia treatment, and cell viability was detected by CCK-8 cell proliferation assay kit, and then grouping experiment was carried out. The cells were randomly divided into four groups. The cells were cultured in different concentration glucose medium under normal oxygen, 5% CO 2 and 37 centigrade for 72 hours to prepare OGD/R model of cell ischemia/reperfusion. The low-glucose control group was cultured in medium containing 5.5 mmol/L glucose. The constant high-glucose group was cultured in medium containing 33.0 mmol/L glucose. The intermittent high-glucose group was cultured in medium containing 33.0 mmol/L glucose for 3 hours then in medium containing 5.5 mmol/L glucose for 2 hours alternately for 3 times during the day, and overnight in medium containing 33.0 mmol/L glucose at night. The hyperosmotic control group was made up of 5.5 mmol/L glucose medium and mannitol. The osmotic pressure was the same as that of the constant high-glucose group, and the effective glucose concentration was the same as that of the normal glucose and oxygen group, so as to eliminate the effect of osmotic pressure changes caused by the high-glucose medium on the results. Cell morphology was observed under inverted phase contrast microscope after 72 hours of cell culture in each group. Cell viability was measured by CCK-8 kit, and apoptotic rate was measured by flow cytometry., Results: The inverted phase contrast microscope showed that the cells in the normal glucose and oxygen control group were plump and refractive, and had obvious nucleus, clear processes and high cell activity. After 6 hours of hypoxia and hypoglycemia treatment, the cells were shrunk, refractive index was poor, the nucleus was unclear, the processes were not clear, and the cell activity was significantly lower than that of normal glucose and oxygen control group (A value: 0.34±0.06 vs. 1.09±0.06, P < 0.01), which indicated that the model of oxygen-glucose deprivation (OGD) was successfully prepared. After 72 hours of culture with different concentrations of glucose, the cells in the low-glucose control group were shrunk, the cell membrane was incomplete, the nucleus was unclear, and number of necrotic cells were more. In the constant high-glucose group, the refractive index of cells was poor, a large number of cells floated, and the nucleus was not obvious. In the intermittent high-glucose group, the cell morphology was normal, the refractive rate of cells was decreased slightly, and the necrotic cells were less. In the hypertonic control group, the cell status was close to that in the constant high-glucose group. Compared with the low-glucose control group or constant high-glucose group,the cell viability in the intermittent high-glucose group was significantly increased (A value: 2.04±0.15 vs. 0.64±0.18, 1.16±0.16, both P < 0.01), the apoptotic rate was significantly decreased [(59.60±2.55)% vs. (78.15±15.77)%, (95.60±0.14)%, both P < 0.05]. There was no significant difference in cell activity or apoptotic rate between the hypertonic control group and the constant high-glucose group [cell activity (A value): 1.07±0.07 vs. 1.16±0.16, apoptotic rate: (87.80±4.53)% vs. (95.60±0.14)%, both P > 0.05]., Conclusions: Intermittent high glucose within a certain range had protective effect on OGD/R neuronal survival.

BACKGROUND Ginsenoside is the major bioactive component of ginseng, which has been proven to be a neuroprotective drug. The aim of this study was to evaluate the therapeutic effect of ginsenoside in a diabetic Goto-Kakizaki (GK) rat model. MATERIAL AND METHODS Twenty GK rats were randomly divided into a diabetic model (DM) group (n=10) and a ginsenoside + DM group (n=10); Wistar rats with the same age and body weight were used as the control (CON) group (n=10). Food and water intake, body weight, and blood fasting plasma glucose were measured. The Morris water maze test was used to detect learning and memory functions of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the hippocampus were analyzed after ginsenoside treatment. RESULTS The blood glucose, body weight, Morris correlation index, SOD, MDA, and other test results were increased in the diabetic rats. Ginsenoside ameliorated diabetic cognitive decline. CONCLUSIONS The possible mechanism was related to inhibiting brain oxidative/nitrosative damage and affecting the expression of the cytokines IL-1β, IL-6, and TNF-α.

Background: The use of PCI in early operable patients with small cell lung cancer (SCLC) is still controversial. Therefore, we conducted a systematic review with meta-analysis to investigate the effects of PCI in resected SCLC patients. Methods: Relevant studies were identified from PubMed and EMBASE databases, the pooled hazard risks were obtained by the random-effects model. We also analyzed the brain metastasis (BM) risk in p-stage I patients without PCI. Results: Five retrospective studies were identified and a total of 1691 patients were included in our analysis, 315 of them received PCI. For all the resected patients, PCI was associated with improved overall survival (HR: 0.52, 95% CI: 0.33-0.82), and reduced brain metastasis risk (RR: 0.50, 95%CI: 0.32-0.78). However, with regard to p-stage I patients, no survival benefit was brought by PCI (HR: 0.87, 95% CI: 0.34-2.24). Moreover, the pooled analysis of 7 studies found that the 5-year brain metastasis risk was relatively low (12%, 95% CI: 8%-17%) for p-stage I patients without PCI. Conclusions: PCI might be associated with a favorable survival advantage and reduced BM risk in complete resected SCLC patients, except for p-stage I patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Concurrent chemoradiotherapy (CCRT) using conventional platinum-based doublets are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. We previously reported a phase I trial of CCRT using S-1, an oral 5-fluorouracil derivative, which yielded well safe and active outcomes., Methods: Patients with histologically confirmed esophageal cancer, who were age of 70 years or older with performance status (PS) score of 0-2 or age of 66 to 69 with PS score of 2, were eligible for this Phase II trial. Radiotherapy was delivered in 1.8 Gy per fraction to a total dose of 54 Gy. Concurrently, S-1 was administered at 70 mg/m 2 on days 1-14 and 29-42. The primary end point was 2-year overall survival rate., Results: Thirty patients were enrolled, and 28 patients completed the full course of radiotherapy. No grade 4 toxicity or treatment-related death occurred. The grade 3 toxicities included esophagitis (16.7%), leucopoenia (13.3%), neutropenia (10%), anaemia (3.3%), pneumonitis (3.3%) and fatigue (3.3%). The median progression-free survival time and median survival time was 19 and 24 months, respectively. The 2-year overall survival rate was 45.1%, which exceeded the predefined threshold of 2-year OS 35% and met the primary end point of the study., Conclusions: The results suggest that CCRT using S-1 is effective with mild toxicity in elderly patients with esophageal cancer. A phase III trial is needed to further evaluate this regimen., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

In the present study, clips were used as markers to evaluate displacement differences between proximal and distal ends of esophageal tumors and to test whether their internal target volume (ITV) margins should be determined separately. A total of 23 patients with mid-upper thoracic esophageal squamous-cell carcinoma, a tumor length of ≤8 cm and an esophageal lumen suitable for endoscopic ultrasonography were recruited for the present study. Clips were implanted endoscopically at the proximal and distal ends of the esophageal tumor (upper and lower clips). In a further exploratory study on 16 of the patients, a third clip was placed at the distal esophagus 2 cm above the gastro-esophageal junction (GEJ) (cardiac clip). The clips were contoured for all 10 phases of the four-dimensional computed tomography and the maximum displacements of the clip centroids among different breathing phases in left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions were marked as x, y and z, respectively. The ITV margins that covered 95% of the LR, SI and AP motion were 2.89, 5.00 and 2.36 mm, respectively. Axial displacement (y) was greater than radial displacement (x, z; P<0.05). It was also revealed that LR(x), SI(y) and AP(z) displacement of cardiac clips was greater than that of upper or lower clips (P<0.05). Differences in the axial and radial displacement of the upper and lower clips indicated that axial and radial ITV margins should be determined separately. However, further study is required on patients in whom the distal tumor end is located in proximity to the GEJ.

Eukaryotes initiate autophagy to cope with the lack of external nutrients, which requires the activation of the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase Sirtuin 1 (Sirt1). However, the mechanisms underlying the starvation-induced Sirt1 activation for autophagy initiation remain unclear. Here, we demonstrate that glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a conventional glycolytic enzyme, is a critical mediator of AMP-activated protein kinase (AMPK)-driven Sirt1 activation. Under glucose starvation, but not amino acid starvation, cytoplasmic GAPDH is phosphorylated on Ser122 by activated AMPK. This causes GAPDH to redistribute into the nucleus. Inside the nucleus, GAPDH interacts directly with Sirt1, displacing Sirt1's repressor and causing Sirt1 to become activated. Preventing this shift of GAPDH abolishes Sirt1 activation and autophagy, while enhancing it, through overexpression of nuclear-localized GAPDH, increases Sirt1 activation and autophagy. GAPDH is thus a pivotal and central regulator of autophagy under glucose deficiency, undergoing AMPK-dependent phosphorylation and nuclear translocation to activate Sirt1 deacetylase activity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study investigated the correlation of preoperative plasma fibrinogen level with distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). A total of 255 patients with ESCC who underwent surgery in Zhejiang cancer hospital (Hangzhou, China), between October 2006 and December 2009, were evaluated in this retrospective study. Population controls were selected from a pool of cancer-free subjects in the same region. Each patient and cancer-free people provided 3-mL pretreatment blood. Plasma fibrinogen level was measured by the Clauss method. The effects of hyperfibrinogenemia on locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. The proportion of hyperfibrinogenemia was higher in ESCC patients than those in controls (40.4% vs 13.6%). Subjects with hyperfibrinogenemia had a significantly higher risk of ESCC than those with normal plasma fibrinogen level (adjust OR = 4.61; 95% CI = 3.02-7.01, P < 0.001) after adjusted for age, sex and smoking status. The Kaplan-Meier curves showed that patients with hyperfibrinogenemia had worse DMFS, RFS and OS (P < 0.001). Tumor length, lymph node metastasis and plasma fibrinogen level were independent prognostic factors of ESCC (P < 0.05). Increased plasma fibrinogen level was significantly associated with elevated risk of ESCC. Preoperative plasma fibrinogen level was a predictor of distant metastasis and independently associated with prognosis of patients with ESCC.

This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

Objective: To investigate the association between thromboxane A2 receptor (TXA2R) gene promoter rs2271875, rs768963 polymorphism and acute cerebral infarction in Chinese Han population., Methods: A prospective study was conducted. From October 2009 to May 2013, 223 patients with cerebral infarction (cerebral infarction group) and 142 cohorts with normal physical examination results (control group) from Taizhou City Central Hospital in Zhejiang Province were enrolled. Triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined by enzymatic colorimetry, whereas blood glucose was determined with hexokinase. The genotypes of rs2271875 and rs768963 polymorphism in TXA2R gene were detected by the polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. Differences in gender, age, serum TG, TC, HDL-C, LDL-C, concentration of blood glucose, and blood pressure (systolic pressure, diastolic pressure) between cerebral infarction group and control group were compared as well as TXA2R promoter rs2271875, rs768963 genotype and allele frequencies distribution., Results: The significant differences in males (147 cases vs. 57 cases, χ(2)=23.385, P=0.000), serum TG (2.02±1.14 mmol/L vs. 1.56±0.79 mmol/L, t=4.663, P=0.000), blood glucose (6.40±2.50 mmol/L vs. 5.28±0.92 mmol/L, t=6.084, P=0.000), systolic pressure (146.64±21.34 mmHg vs. 135.73±18.09 mmHg, t=5.234, P=0.000), diastolic blood pressure (86.29±11.79 mmHg vs. 80.74±11.23 mmHg, t=4.468, P=0.000) between cerebral infarction patients and controls were found. The results from multi-logistic regression analysis suggested that male was an independent risk factor for cerebral infarction [odds ratio (OR) 3.300, 95% confidence interval (95%CI) 1.905-5.175, P=0.000]. There were statistically significant differences between infarction group and the control group both in aspects of genotype (TT: 0.112 vs. 0.183, TC: 0.498 vs. 0.535, CC: 0.390 vs. 0.282, χ(2)=6.298, P=0.043) and the allele frequency distribution (T: 0.361 vs. 0.451, C: 0.639 vs. 0.549, χ(2)=5.839, P=0.016) of TXA2R gene rs768963. No statistical significant difference was found in rs2271875 in respect of genotype (GG: 0.336 vs. 0.352, GA: 0.480 vs. 0.451, AA: 0.184 vs. 0.197, χ (2)=0.302, P=0.859) and the allele frequency distribution (G: 0.576 vs. 0.577, A: 0.424 vs. 0.423, χ(2)=0.001, P=0.974). Coefficient of both linkage disequilibrium (D') of rs2271875 and rs768963 was 0.684. When the pair was haplotype AT, the frequency in the infarction group was significantly lower than that in the control group (0.034 vs. 0.081, χ(2)=7.883, P=0.005)., Conclusions: rs768963 gene mutation, but not that of the rs2271875, showed significant correlation with the occurrence of cerebral infarction. There was a loose linkage disequilibrium between rs2271875 and rs768963 of TXA2R. Haplotype AT reduces the risk of cerebral infarction.

Objective: To investigate the association of matrix metalloproteinase-3 (MMP-3) serum level and the promoter 5A/6A polymorphism of the MMP-3 gene with atherosclerotic cerebral infarction (ACI) in a Chinese Han population., Methods: Two hundred and fifteen patients with acute ACI from the Department of Neurology of Taizhou Hospital and 226 healthy controls were included in the study. Serum MMP-3 level was measured by enzyme-linked immunosorbent assay (ELISA). Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the common 5A/6A functional promoter polymorphism of the MMP-3 gene., Results: The genotype distribution of the MMP-3 promoter 5A/6A polymorphism between the ACI patients group and the control group was significantly different (chi (2)= 9.389, P= 0.002). The frequencies of the 5A allele were 14.2% and 7.7% in the ACI patients group and the control group respectively (chi (2)= 9.430, P= 0.002). Serum level of MMP-3 in the ACI patients group was significantly higher than that in the control group (t= 24.867, P= 0.000). Among the ACI patients group, serum MMP-3 levels also had significant difference between the 5A/6A+ 5A/5A and the 6A/6A genotype (t= 2.057, P= 0.041)., Conclusion: The present findings suggest that serum level of MMP-3 obviously increased within 48 hours of ischemic stroke and the genetic polymorphism of 5A/6A in the MMP-3 promoter is associated with ACI and MMP-3 expression in the Chinese Han population.

In order to evaluate the possibility of using Cr³⁺ co-doping to modify the emission properties of Pr³⁺-based quantum cutting phosphors, which emit one ultraviolet (UV) and one visible photon from each vacuum-UV photon absorbed, into phosphors that emit two visible photons, the optical spectroscopies between 150 and 750 nm of CaAl₁₂O₁₉:M³⁺ (M = Pr,Cr) were investigated and compared with those of SrAl₁₂O₁₉:M³⁺ using synchrotron radiation as one of the excitation sources. When Pr³⁺ is excited to its 4f5d states, cascade emission of UV photons from the ¹S₀ state followed by visible photons from the ³P₀ state are both observed in (Ca,Sr)Al₁₂O₁₉:Pr³⁺. Similar to SrAl₁₂O₁₉:M³⁺, there exist desirable spectral overlaps between Pr³⁺ ¹S₀ emissions and the Cr³⁺ higher multiplet absorptions in CaAl₁₂O₁₉, which should be favourable to the energy transfer from Pr³⁺ ¹S₀ to Cr³⁺, converting the UV photon from Pr³⁺ ¹S₀ into the red Cr³⁺ emission. However, the host absorption band and the Cr³⁺-related charge transfer band have an unfavourable overlap with the Pr³⁺ 4f5d states in the vacuum-UV region, preventing efficient selective Pr³⁺ excitation under radiation of Xe discharge, a prerequisite for the quantum cutting process.