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Zhida Bian,1,2,&ast; Hui Li,3,4,&ast; Yanlong Liu,5,&ast; Yanjun Cao,2 Yanxia Kang,2 Yongjun Yu,2 Feng Zhang,1,2 Cunbao Li,1 Yimin Kang,1 Fan Wang2,4 1Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, 010110, People’s Republic of China; 2Beijing Hui-Long-Guan Hospital, Peking University, Beijing, 100096, People’s Republic of China; 3Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, People’s Republic of China; 4Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital, Urumqi, 830063, People’s Republic of China; 5School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fan WangBeijing Hui-Long-Guan Hospital, Peking University, Beijing, 100096, People’s Republic of ChinaTel +86 10 83024429; +86 991-4609006Fax +86 10 62716285; +86 991-4609100Email FanWang@bjmu.edu.cnYimin KangPsychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, 010110, People’s Republic of ChinaTel/Fax +86 471-6657548Email kangym@immu.edu.cnBackground: The occurrence of depression was related with a state of mild hypoxia for a long time. Hypoxia-inducible factor-2α (HIF-2α) modulates the process from acute to chronic hypoxia, consequently regulating changes in inducible nitric oxide synthase (iNOS). Increasing levels of iNOS combined with major depressive disorder (MDD) have been associated with the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which increase the severity of depression.Objective: The aim was to investigate whether depressive symptoms might be improved by regulating HIF-2α levels to decrease the degree of oxidative stress and inflammation using electroconvulsive therapy (ECT).Methods: In this observational study, 49 MDD patients were divided into the ECT group (n=32) and control group (n=17). The Hamilton Depression Rating Scale (HAMD) was used to evaluate depressive symptoms of patients at enrollment and after 2 weeks of treatment. The levels of HIF-2α, NOS, IL-6, and TNF-α in plasma were analyzed accordingly.Results: The total score in each dimension of HAMD decreased more efficiently in the ECT group than in the control group (p < 0.05). The plasma levels of IL-6 in the ECT group were notably decreased after the 2-week treatment (t = 3.596, p = 0.001). The decreased trend to statistical significance of HIF-2α was observed after treatment in the ECT group (p = 0.091).Conclusion: The present study demonstrated that the therapeutic effects of long-term ECT therapy for MDD may further benefit from and contribute to the improvement of MDD-associated chronic hypoxia.Keywords: major depressive disorder, modified electroconvulsive therapy, hypoxia-inducible factor, neuroinflammation, oxidative stress

Research has confirmed that plasma albumin (Alb), prealbumin (PA) and fibrinogen (Fib) are involved in regulating the occurrence and development of various tumors. Their levels in peripheral blood are related to the survival outcome and treatment response of patients, but the accuracy and specificity of single application have yet to be fully realized. A growing amount of evidence indicates that predictors such as preoperative fibrinogen to prealbumin ratio (FPR), fibrinogen to albumin ratio (FAR) or albumin to fibrinogen ratio (AFR) are emerging as comprehensive indicators. Indeed, their components play a key regulatory role in the progression of colorectal cancer (CRC). Preoperative FPR, FAR or AFR levels, therefore, are expected to become new biomarkers for prognosis evaluation and curative effect prediction for CRC patients and are significant in the guidance they could provide for the development of individualized treatment strategies.

Cancer is a worldwide problem that threatens human health. Radiotherapy plays an important role in a variety of cancer treatment methods. The administration of radiotherapy can alter the differentiation pathways and functions of T cells, which in turn improves the immune response of T cells. Radiotherapy can also induce up-regulation of PD-L1 expression, which means that it has great potential for enhancing the therapeutic effect of anti-PD-1/PD-L1 inhibitors and reducing the risk of drug resistance toward them. At present, the combination of radiotherapy and anti-PD-1/PD-L1 inhibitors has shown significant therapeutic effects in clinical tumor research. This review focuses on the mechanism of radiotherapy on T cells reported in recent years, as well as related research progress in the application of PD-1/PD-L1 blockers. It will provide a theoretical basis for the rational clinical application of radiotherapy combined with PD-1/PD-L1 inhibitors.

This study analyzed the trend in semen quality of infertile male patients in Wenzhou, China, based on the data obtained from 38 905 patients during 2008-2016 in The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). The results showed that only 24.9% of the patients had normal semen quality. For the semen quality of infertile male patients, that of the workers and 40-year-olds was significantly worse than the other occupational and age groups. For all the infertile patients, low semen volume, asthenozoospermia, and teratozoospermia accounted for 8.4%, 50.5%, and 54.1%, respectively. During 2008-2016, the annual mean percentage of fast forward motile spermatozoa, percentage of total forward motile spermatozoa, and percentage of spermatozoa with normal morphology decreased linearly with slopes of -2.11, -2.59, and -0.70, respectively. The proportion of patients with asthenozoospermia and multi-abnormal spermatozoa increased during 2008-2016 with slopes of 4.70 and 4.87, respectively, while for low semen volume, it decreased with a slope of -0.47 in the same time period. The proportion of patients with teratozoospermia increased from 2008 to 2011 and from 2011 to 2016 with slopes of 17.10 and 2.09, respectively. In general, the deteriorating trend of semen quality of infertile male patients in Wenzhou was obvious. Future efforts should be made to reveal the adverse influences on semen quality, such as occupational exposure, environmental quality, and living habits. Furthermore, more pervasive reproduction health education is necessary.

Background Cigarette smoking has shown to be associated with sleep disturbance, especially prolonged sleep onset latency (SOL). Cigarette smoking stimulates the release of dopamine (DA) and serotonin (5-HT), which might promote awakening and inhibit rapid eye movement sleep. Dopamine transporter (DAT) and serotonin transporter play a key role in the reuptake of DA and 5-HT from the synaptic cleft into presynaptic neurons. However, the relationship among cigarette smoking, sleep disturbance and neurotransmitters has never been investigated in human cerebrospinal fluid (CSF). Methods A total of 159 Chinese male subjects (81 active smokers and 78 non-smokers) who would undergo lumbar puncture before the surgery of anterior cruciate ligament reconstruction were recruited and 5mL-CSF samples were collected incidentally. CSF levels of DA, DAT, 5-HT, and serotonin transporter were measured using radioimmunoassay and ELISA. Sociodemographic data and the Pittsburgh Sleep Quality Index (PSQI) scale were collected before surgery. Results PSQI global scores, SOL, and CSF DA levels were significantly higher in active smokers compared to non-smokers (2.00 [1.00-4.75] scores vs 4.00 [3.00-6.00] scores, p = 0.001; 10.00 [5.00-15.00] minutes vs 15.00 [10.00-30.00] minutes, p = 0.002; 87.20 [82.31-96.06]ng/mL vs 107.45 [92.78-114.38] ng/mL, p < 0.001), while CSF DAT levels were significantly lower in active smokers (0.35 [0.31-0.39] ng/mL vs 0.29 [0.26-0.34] ng/mL, p < 0.001). Conclusion Cigarette smoking was indeed associated with sleep disturbance, shown by prolonged SOL, higher DA levels and lower DAT levels in CSF of active smokers.

Colorectal cancer is one of the most common malignant tumors and, hence, has become one of the most important public health issues in the world. Treatment with immune checkpoint inhibitors (ICIs) successfully improves the survival rate of patients with melanoma, non‐small‐cell lung cancer, and other malignancies, and its application in metastatic colorectal cancer is being actively explored. However, a few patients develop drug resistance. Predictive molecular markers are important tools to precisely screen patient groups that can benefit from treatment with ICIs. The current article focused on certain important predictive molecular markers for ICI treatment in colorectal cancer, including not only some of the mature molecular markers, such as deficient mismatch repair (d‐MMR), microsatellite instability‐high (MSI‐H), tumor mutational burden (TMB), programmed death‐ligand‐1 (PD‐L1), tumor immune microenvironment (TiME), and tumor‐infiltrating lymphocytes (TILs), but also some of the novel molecular markers, such as DNA polymerase epsilon (POLE), polymerase delta 1 (POLD1), circulating tumor DNA (ctDNA), and consensus molecular subtypes (CMS). We have reviewed these markers in‐depth and presented the results from certain important studies, which suggest their applicability in CRC and indicate their advantages and disadvantages. We hope this article is helpful for clinicians and researchers to systematically understand these markers and can guide the treatment of colorectal cancer., Predictive molecular markers are important tools to precise screen of patient groups who can benefit from immune checkpoint inhibitors treatment. This article focused on some important predictive molecular markers for ICI treatment in colorectal cancer, which included not only some mature molecular markers such as deficient mismatch repair (d‐MMR) or microsatellite instability‐high (MSI‐H), tumor mutational burden (TMB), programmed death‐ligand 1(PD‐L1), and tumor immune microenvironment (TiME) or tumor‐infiltrating lymphocytes (TILs), but also some novel molecular markers, such as POLE or POLD1, circulating tumor DNA and consensus molecular subtypes (CMS). We have made in‐depth reviews for these markers, which included some important studies in the past, possibility of their application in CRC, the advantages and disadvantages of their application as molecular markers, and the difficulties they are currently facing.

Objective: Cigarette smoking might accelerate cognitive impairment; however, this has never been investigated using human cerebrospinal fluid (CSF). We conducted this study to investigate the association between cigarette smoking and cognitive impairment through metal ions in CSF.Methods: We obtained 5-ml CSF samples from routine lumbar puncture procedures in patients undergoing anterior cruciate ligament reconstruction before surgery in China. A total of 180 Chinese males were recruited (80 active smokers and 100 non-smokers). We measured specific cigarette-related neurotoxic metal ions in CSF, including iron, copper, zinc, lead, aluminum, and manganese. Sociodemographic data and history of smoking were obtained. The Montreal Cognitive Assessment (MoCA) was applied.Results: Active smokers had fewer years of education (11.83 ± 3.13 vs. 13.17 ± 2.60, p = 0.01), and higher age (33.70 ± 10.20 vs. 29.76 ± 9.58, p = 0.01) and body mass index (25.84 ± 3.52 vs. 24.98 ± 4.06, p =0.03) than non-smokers. Compared to non-smokers, active smokers had significantly higher CSF levels of iron, zinc, lead, and aluminum and lower MoCA scores (all p < 0.05). Average daily numbers of cigarettes smoked negatively correlated with the MoCA scores (r = −0.244, p = 0.048). In young smokers, CSF manganese levels negatively correlated with MoCA scores (r = −0.373, p = 0.009).Conclusions and Relevance: Cigarette smoking might be associated with male cognitive impairment, as shown by lower MoCA scores and higher levels of CSF iron, zinc, lead, and aluminum in active smokers. This might be early evidence of cigarette smoking accelerating male cognitive impairment.

Background Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. However, no biomarker of impulsivity available so far. This study explored the association between cerebrospinal fluid (CSF) fibroblast growth factor 21 (FGF21), a key hormonal mediator of the stress response, and impulsivity in healthy subjects. Methods A total of 126 healthy persons subjected to surgery of anterior cruciate ligament were recruited in the present study. The impulsiveness of the subjects was evaluated by the Chinese version of the Barratt Impulsiveness Scale (BIS)-11 before surgery. CSF and blood samples of the subjects were collected before spinal anesthesia for surgery. The levels of FGF21, serotonin and dopamine in CSF and the level of FGF21 in blood of the subjects were measured by ELISA using commercial kits. Results Negative correlations were found between BIS-11 total score and either FGF21, serotonin or dopamine in CSF. However, BIS-11 total score was not correlated with FGF21 in blood. In addition, FGF21 was positively correlated with serotonin and dopamine in CSF, respectively. Multivariable linear regression models indicated that the decrease of FGF21 level associating with the decrease of serotonin and dopamine level in CSF contributed to the higher impulsivity. Furthermore, receiver operating characteristic curve (ROC) analysis indicated an important role of CSF FGF21 predicting high impulsivity. Conclusions FGF21, serotonin and dopamine in CSF associate with impulsivity in opposite directions. The decrease of CSF FGF21 is related to higher impulsivity, and indicate that CSF FGF21 may predict impulsivity in healthy subjects.

Alcohol dependence (AD) is characterized by compulsive alcohol consumption, which involves behavioral impairments such as aggression. Members of fibroblast growth factor (FGF) 19 superfamily, including FGF19, FGF21, and FGF23, are major endocrine mediators that play an important role in alcohol metabolism and alcohol related disorders. The objective of the present study is to explore the possible associations among the interaction of single nucleotide polymorphisms (SNPs) of the FGF 19 superfamily, AD occurrence, and aggression in patients with AD. A total of 956 subjects were enrolled in this study, including 482 AD patients and 474 healthy controls (HCs). Michigan alcoholism screening test (MAST) was used to measure the level of AD, a Chinese version of the Buss–Perry Aggression Questionnaire was used to evaluate the aggressive behavior of subjects, and MassARRAY@ system was used to genotype rs948992 of FGF19, rs11665841 and rs11665896 of FGF21, rs7955866 and rs11063118 of FGF23. The results showed that AD patients presented a significantly higher level of aggression compared to HCs, and MAST scores were significantly positively associated Buss–Perry aggression scores (r = 0.402, p < 0.001) in AD patients. The interaction of FGF19 rs948992 TC × FGF21 rs11665896 GG presented the high-risk genotype combination predicting the high level of AD. In addition, the interaction of FGF19 rs948992 TC × FGF21 rs11665896 TG × FGF23 rs11063118 TT presented the high-risk genotype combination predicting the high level of aggression in AD patients. Our results added evidence linking the combination of rs948992 TC × rs11665896 TG × rs11063118 TT to aggressive behavior in AD patients and pointed out the potential usefulness of the SNPs of FGF19 superfamily as a predictor for the aggression in AD patients.

Background: Acute liver injury (ALI) involves excessive oxidative stress(OS) and inflammatory responses, leading to a high mortality rate due to lack of effective therapy. Carbon tetrachloride (CCl4) is widely used to induce ALI by induction of reactive oxygen species. Probiotics, including Lactobacillus plantarum ST-III, have been shown to produce antibacterial and antioxidant substances such as organic acids or bacteriocins that reduce liver damage. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (L-P-cs) on CCl4-induced liver injury remains unclear.Methods: Mice were pretreated with L-P-cs or medium for 14days before one dose of 0.2% CCl4 at 10ml/kg body weight delivered by intraperitoneal injection. CCl4-induced liver injury was examined by measuring serum levels of liver transaminases and high mobility-group box 1 protein (HMGB1) and liver histological staining. Inflammation and apoptosis in liver were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and TUNEL staining. Apoptosis in NCTC 1469 cells was detected using CCK8 and western blotting (WB). In liver, OS and endoplasmic reticulum stress(ERS)-related proteins were measured using kits and WB.Results: L-P-cs significantly ameliorated CCl4-induced liver injury and reduced CCl4- induced inflammatory response and apoptosis, consistent with NCTC 1469 cells' results. L-P-cs also restored CCl4-induced increases in cell OS and ERS to normalize liver function. Specifically, L-P-cs pretreatment decreased CCl4-induced increases in nuclear factor (erythroid-2 related) factor 2, HO-1, superoxide dismutase, glucose regulatory protein, and activating transcription factor 6.Conclusion: L-P-cs synergistically improves liver lobule necrosis, hepatocyte inflammation, and apoptosis by reducing liver OS and ERS.

Background: Previous researches have shown that the aberrant expression of Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in tumour tissues may serve as a biomarker for colorectal cancer (CRC) prognosis. However, these previous studies have small sample sizes and lacked validation from independently external populations. We therefore aimed to clarify the prognostic value of MALAT1 expression status in CRC patients using a large cohort and validate the findings with another large external cohort. Methods: The prognostic association between MALAT1 expression status and CRC outcomes was evaluated initially in a prospective cohort in China (n=164) and then validated in an external TCGA population (n=596). In the initial cohort, MALAT1 expression levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Propensity score (PS) adjustment method was used to control potential confounding biases. The prognostic significance was reported as PS-adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI). Results: There was no statistically significant association between MALAT1 expression status and CRC patient overall survival (OS) or disease free survival (DFS) in both initial cohort and external validation cohort populations. When combining these populations together, the results did not change materially. The summarized HRPS-adjusted were 1.010 (95%CI, 0.752-1.355, P=0.950) and 1.170 (95%CI, 0.910-1.502, P=0.220) for OS and DFS, respectively. We performed extensive sensitivity analyses, and demonstrated a very robustness of these results. Conclusions: The MALAT1 expression status was not associated with prognostic outcomes in CRC patients. Our findings did not support a prognostic association of MALAT1 expression with CRC outcomes.

ObjectiveThe conventional preoperative CRT provides local tumor control in most LARC patients. However, long-term survival has not obviously improved. Thus, the optimal neoadjuvant treatment is still controversial. Sandwich therapy may be associated with better efficacy.Methods The present study is a single-center, open-label, phase II, non-randomized trial (Clinical trials number: NCT02022852). Pathological diagnosis of eligible patients were as rectal adenocarcinoma and they were clinically confirmed by MRI as cT3-4NxM0, with distal border located＜10cm from anal verge. Hundred and seventy-two patients between July 2013 and July 2015 were enrolled for the trial. The enrolled patients were non-randomly assigned into two treatment types (arm A and arm B). Patients in arm A received capecitabine-based concurrent CRT 25 fractions. In contrast, arm B patients received sequential therapy as induction CapeOx for two cycles, followed by 25 fractions CRT, finally adding one consolidation CapeOx cycle. After preoperative treatment, TME with different adjuvant therapy types were performed in patients.ResultsWith treatment processing, 48 patients were excluded from the trial due to personal reasons and intolerance to treatment toxicities. Finally, there were 61 patients in arm A and 63 patients in arm B (70.9% vs. 73.2%). The 5-years DFS and OS didn’t show significant difference in two arms. However, the postoperative complications of arms A and B were 4.9% and 17.5% (P=0.027).ConclusionsSandwich therapy may lead more postoperative complications than conventional CRT, so that the safety should further research. Compared with conventional CRT, sandwich therapy doesn’t show significant advantage in survival.

Wind power prediction plays an important role in the impact analysis of wind farm connection to power grid. Aiming at the problems of the Elman neural network in wind power prediction, such as the difficulty in determining the structure and weight parameters and the low prediction accuracy, this paper proposes an improved genetic algorithm to optimize the Elman neural network model. The topological structure and weight parameters of the wind power prediction model based on Elman neural network are optimized and determined, and the effect of wind power prediction based on Elman neural network is also improved. The effectiveness of the proposed method is verified by comparing the simulation results with the real values.

BackgroundThe prognostic stratification of colon cancer using only the tumor-node-metastasis (TNM) stage has some limitations. We sought to increase the accuracy of stratifying patients with stage III colon cancer by constructing a prognostic model combining carcinoembryonic antigen (CEA) with TNM.MethodsWe retrospectively analyzed the data generated from stage III colon cancer patients who had early postoperative CEA measurement from 21 to 100 days after surgery from 2006 to 2017. CEA value was processed using restricted cubic splines (RCS) method. The prognostic model was developed using cox proportional hazards regression.ResultsThe time later than 20 days after surgery was optimal for measuring CEA, which was determined by comparing the prognostic value for preoperative and postoperative CEA (N = 2,049), and by evaluating the relationship between the hazard ratio (HR) and postoperative CEA measuring time. Postoperative CEA, T stage and N stage were selected into the final model, and the mean integrated-AUC (iAUC) was 0.78 with 1,000 × bootstrap resampling, which was higher than the model using only T and N stages (TN model; mean iAUC, 0.66). The net reclassification improvement (NRI) was 15% when compared with TN model. Patients could be divided into high and low risk groups by the model, and 3-year disease-free survival (DFS) were 53.7% and 87.0%, respectively (HR, 4.30; 95% CI, 2.65 to 6.96; P < 0.001). Similar results were found in the validation set.ConclusionsStage III colon cancer could be stratified more accurately using the new prognostic model combining postoperative CEA with T and N stage.

Background: During an epidemic, both frontline and non-frontline medical staff endure stressful work circumstances that render their mental health a major public health concern. This study aims at investigating and comparing the prevalence and severity of mental health symptoms (i.e., anxiety, depression and insomnia) between frontline medical staff and non-frontline medical staff during the coronavirus disease 2019 (COVID-19) outbreak. It also seeks to evaluate the association of their mental health with occupational stress.Methods: A cross-sectional study was conducted in Wenzhou, China from 2020 February 16th to 2020 March 2th. A total of 524 medical staff responded to the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire, the Insomnia Severity Index, the Occupational stress Questionnaire, and a demographic data form. Data were principally analyzed with logistic regression.Results: Of the 524 participants, 31.3% reported depression, 41.2% reported anxiety, and 39.3% reported insomnia. Compared with the citizens during the COVID-19 epidemic, medical staff experienced higher level of anxiety, depression and insomnia, especially the frontline medical staff. Furthermore, male, married medical staff with poorer physical health reported lower mental health. Frontline medical staff endorsed higher self-reported occupational stress, especially higher occupational hazards, than non-frontline medical staff. In addition, four indicators on occupational stress (working intensity, working time, working difficulty and working risk) were correlated positively with mental health symptoms. Regression analyses found a significant association between occupational stress and mental health symptoms in both frontline and non-frontline medical staff during COVID-19 outbreak.Conclusion: The results indicated that during the COVID-19 epidemic, medical staff experienced higher levels of anxiety, depression and insomnia than citizens, and their occupational stress had positive effects on their psychological distress. These findings emphasize the importance of occupational stress management interventions to decrease the risk of developing mental health problems among the medical staff during a biological disaster.

Background: Increasing evidence indicates that inflammation and nutritional status are associated with survival outcomes in patients with colorectal cancer (CRC). This study aimed to investigate the prognostic values of preoperative inflammatory and nutritional factors and develop a prognostic model individually predicting overall survival (OS) and disease-free survival (DFS) in patients with CRC. Methods: We retrospectively collected data on patients with CRC who underwent radical surgery. Independent prognostic inflammatory and nutritional markers were identified and novel prognostic models were developed incorporating the identified factors. The discriminative ability and model-fitting performance were evaluated by receiver operating characteristic curves and Akaike information criteria. Clinical usefulness was assessed by decision curve analysis. Results: A total of 400 eligible patients were identified. Multivariate analysis identified pN stage, tumor differentiation grade, neutrophil count, and body mass index as independent prognostic factors for OS, and pN stage, tumor differentiation grade, neutrophil count, neutrophil-lymphocyte ratio, and serum albumin as prognostic factors for DFS. The combined inflammatory and nutritional prognostic model showed better discriminative ability, model-fitting performance, and net benefits than the inflammatory and nutritional models alone, and the American Joint Committee on Cancer (AJCC) 8th TNM classification for predicting OS and DFS. Conclusion: Preoperative nutritional and inflammatory factors have significant prognostic value in patients with CRC. A novel prognostic model incorporating preoperative inflammatory and nutritional markers provides better prognostic performance than the AJCC 8th TNM classification. A novel nomogram incorporating preoperative inflammatory and nutritional markers can individually predict OS and DFS in patients with CRC.

When large-scale wind power is transmitted through ultra-high voltage direct current (UHVDC) system, transient overvoltage (TOV) problems caused by events such as commutation failure and DC blocking seriously affect the safe operation of the system and constrain the power transmission capacity. Accurate modeling of the system is the basis for analyzing the transient overvoltage characteristics of the system. In this paper, the modeling methods of the main components of the system, especially UHVDC transmission line and large-scale wind power cluster, were sorted out in detail. The advantages and disadvantages of various modeling methods were reviewed. Feasible optimization schemes were proposed for future modeling of large-scale wind power connected UHVDC system.

BACKGROUND Determining the status of lymph node (LN) metastasis in rectal cancer patients preoperatively is crucial for the treatment option. However, the diagnostic accuracy of current imaging methods is low. PURPOSE To develop and test a model for predicting metastatic LNs of rectal cancer patients based on clinical data and MR images to improve the diagnosis of metastatic LNs. STUDY TYPE Retrospective. SUBJECTS In all, 341 patients with histologically confirmed rectal cancer were divided into one training set (120 cases) and three validation sets (69, 103, 49 cases). FIELD STRENGTH/SEQUENCE 3.0T, axial and sagittal T2 -weighted turbo spin echo and diffusion-weighted imaging (b = 0 s/mm2 , 800 s/mm2 ) ASSESSMENT: In the training dataset, univariate logistic regression was used to identify the clinical factors (age, gender, and tumor markers) and MR data that correlated with LN metastasis. Then we developed a prediction model with these factors by multiple logistic regression analysis. The accuracy of the model was verified using three validation sets and compared with the traditional MRI method. STATISTICAL TESTS Univariate and multivariate logistic regression. The area under the curve (AUC) value was used to quantify the diagnostic accuracy of the model. RESULTS Eight factors (CEA, CA199, ADCmean, mriT stage, mriN stage, CRM, EMVI, and differentiation degree) were significantly associated with LN metastasis in rectal cancer patients (P

Cigarette smoking has been shown to be associated with sleep disorders and the related neuropathogenesis including neuroinflammation. Previous studies showed that pro- and anti-inflammatory cytokines are physiologically important in maintaining circadian function. In addition, sleep deprivation leads to immune dysregulations. However, no study has been published yet by using cerebrospinal fluid (CSF) biomarkers of neuroinflammation to investigate the relationship between active cigarette smoking and sleep disorders.CSF tissues from subjects of 191 male subjects (non-smokers n = 104; active smokers n = 87) receiving local anesthesia before surgery for anterior cruciate ligament injuries were obtained after the assessment of clinical information and Pittsburgh Sleep Quality Index (PSQI). The levels of tumor necrosis factor alpha (TNFα), Interleukin (IL) 1 beta (IL1β), IL2, IL4, IL6 and IL10 were measured using radioimmunoassay and ELISA.PSQI scores were significantly higher in active smokers than that in non-smokers (p 0.001, Cohen's d = 0.63). Significantly higher levels of CSF TNFα were found in active smokers compared to non-smokers (28 ± 1.97 vs. 22.97 ± 2.48, p 0.05, Cohen's d = 2.23). There was a positive correlation between CSF IL1β levels and PSQI scores in non-smokers (r = 0.31, p = 0.01, adjustment R-Squared = 0.11).This is the first study to reveal the association between higher CSF TNFα levels and poorer sleep quality in active smoking. In addition, CSF IL1β levels might be a potential biomarker in central nervous system for circadian dysregulation.

BACKGROUND AND AIM Differentially expressed (DE) genes detected at the population-level through case-control comparison provide no information on the dysregulation frequencies of DE genes in a cancer. In this work, we aimed to identify the genes with universally upregulated or downregulated expressions in colorectal cancer (CRC). METHODS We firstly clarified that DE genes in an individual cancer tissue should be the disease-relevant genes, which are dysregulated in the cancer tissue in comparison with its own previously normal state. Then, we identified DE genes at the individual level for 2233 CRC samples collected from multiple data sources using the RankComp algorithm. RESULTS We found 26 genes that were upregulated or downregulated in almost all the 2233 CRC samples and validated the results using 124 CRC tissues with paired adjacent normal tissues. Especially, we found that two genes (AJUBA and EGFL6), upregulated universally in CRC tissues, were extremely lowly expressed in normal colorectal tissues, which were considered to be oncogenes in CRC oncogenesis and development. Oppositely, we found that one gene (LPAR1), downregulated universally in CRC tissues, was silenced in CRC tissues but highly expressed in normal colorectal tissues, which were considered to be tumor suppressor genes in CRC. Functional evidences revealed that these three genes may induce CRC through deregulating pathways for ribosome biogenesis, cell proliferation, and cell cycle. CONCLUSIONS In conclusion, the individual-level DE genes analysis can help us find genes dysregulated universally in CRC tissues, which may be important diagnostic biomarkers and therapy targets.

Diabetic nephropathy (DN) is one of general and common complication of diabetes, which severely affects the physical and mental health of diabetic patients. Fibroblast growth factor 1 (FGF1), an effective control agent of blood glucose, plays an effective treatment role on diabetes‐induced renal injury. But the specific molecule mechanism underlying it is still unclear. Since induction of cellular stress is the main and common mechanism of diabetes‐induced complication, we hypothesized that reduction of cellular stress is also the molecular mechanism of FGF1 treatment for DN. Here, we have further confirmed that FGF1 significantly ameliorated the diabetes‐induced renal interstitial fibrosis and glomerular damage. The expression levels of collagen and α‐smooth muscle actin (α‐SMA) also dramatically induced in kidney from db/db mice, but these effects were blocked by FGF1 administration. Our mechanistic investigation had further revealed that diabetes significantly induced oxidative stress, nitrosative stress, and endoplasmic reticulum (ER) stress with upregulation of malondialdehyde (MDA), nitrotyrosine level, ER stress makers and downregulation of antioxidant capacity (AOC). FGF1 treatment significantly attenuated the effect of diabetes on cellular stress. We conclude that FGF1‐associated glucose decreases and subsequent reduction of cellular stress is the another potential molecule mechanism underlying FGF1 treatment for DN.

Histone methylation is closely associated with the occurrence of cancer. Histone H3 trimethylation at lysine 4 (H3K4me3) has been reported to modulate the expression of tumor-associated expression and be altered during the progression of several human cancers. WD Repeat Domain 82 (Wdr82), a key epigenetics-associated factor, is a component of the H3K4me3 methyltransferase complex. An aim of the present study was to determine H3K4me3 and Wdr82 expression and their clinical significances in colorectal cancer (CRC). Immunohistochemistry results demonstrated that the expression level of the H3K4me3 and Wdr82 were significantly decreased in CRC tissues compared with paired noncancerous tissues from 123 patients with CRC. Furthermore, the negative expression of H3K4me3 and Wdr82 expression were significantly associated with lymph node (n=33, P=0.0001) and liver metastasis (n=30, P=0.0001). Additionally, multivariate Cox regression analysis indicated that the low expression level of H3K4me3 or Wdr82 was associated with reduced overall survival (OS, P

Background/Aims: Neonatal hypoxia-ischemia (HI) causes severe brain damage and significantly increases neonatal morbidity and mortality. Increasing evidences have verified that stem cell-based therapy has the potential to rescue the ischemic tissue and restore function via secreting growth factors after HI. Here, we had investigated whether intranasal neural stem cells (NSCs) treatment improves the recovery of neonatal HI, and NSCs overexpressing basic fibroblast growth factor (bFGF) has a better therapeutic effect for recovery than NSCs treatment only. Methods: We performed permanent occlusion of the right common carotid artery in 9-day old ICR mice as animal model of neonatal hypoxia-ischemia. At 3 days post-HI, NSC, NSC-GFP, NSC-bFGF and vehicle were delivered intranasally. To determine the effect of intranasal NSC, NSC-GFP and NSC-bFGF treatment on recovery after HI, we analyzed brain damage, sensor-motor function and cell differentiation. Results: It was observed that intranasal NSC, NSC-GFP and NSC-bFGF treatment decreased gray and white matter loss area in comparison with vehicle-treated mouse. NSC, NSC-GFP and NSC-bFGF treatment also significantly improved sensor motor function in cylinder rearing test and adhesive removal test, however, NSC-bFGF-treatment was more effective than NSC-treatment in the improvement of somatosensory function. Furthermore, compared with NSC and NSC-GFP, NSC-bFGF treatment group appeared to differentiate into more neurons. Conclusion: Taken together, intranasal administration of NSCs is a promising therapy for treatment of neonatal HI, but NSCs overexpressing bFGF promotes the survival and differentiation of NSCs, and consequently achieves a better therapeutic effect in improving recovery after neonatal HI.

// Weinan Xue 1, * , Jingwen Li 1, * , Fan Wang 2, * , Peng Han 1 , Yanlong Liu 1 and Binbin Cui 1 1 Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China 2 Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, 150081, China * These authors contributed equally to this work Correspondence to: Binbin Cui, email: binbincuihrb@126.com Yanlong Liu, email: yanlliu@yahoo.com Keywords: biomarkers, colon adenocarcinoma, expression profiles, long non-coding RNA Received: July 18, 2017 Accepted: August 27, 2017 Published: September 19, 2017 ABSTRACT Colon cancer is the most common type of gastrointestinal cancer and is still the leading cause of cancer-related mortality worldwide. Long non-coding RNAs (lncRNAs) have been proved to be superior biomarkers in cancer diagnosis and prognosis than miRNAs and protein-coding genes. In the current study, our objective was to detect novel lncRNA biomarkers by analyzing lncRNA expression profiles and clinical data in a large cohort of patients with colon patients from The Cancer Genome Atlas (TCGA). By using Cox regression analysis, we identified two lncRNAs ( SNHG6 and CTD-2354A18.1 ) which could be independent prognostic factors for predicting clinical outcome in colon adenocarcinoma. Then a linear combination of these two lncRNA biomarkers ( SNHG6 and CTD-2354A18.1 ), termed two-lncRNA signature, was developed in the training set as a predictor for OS in patients with colon adenocarcinoma, and validated in the testing set and the entire patient set. This two-lncRNA signature demonstrated significant prognostic performance in both the testing set and the entire patient set which classified the patients into two groups with significantly different OS. The multivariate and stratified analysis suggested that the prognostic value of the two-lncRNA signature was independent of other traditional clinical variables. Functional analysis suggested that these two lncRNA biomarkers might be mainly involved in transcription/translation-related or DNA repair-related biological processes. In summary, our results warrant further studies on these lncRNAs that will improve our understanding of the mechanisms associated with pathogenesis and progression of colon adenocarcinoma.

// Jian Chen 1, 2, * , Zhouguang Wang 2, * , Yuqin Mao 2, * , Zengming Zheng 1, 2 , Yu Chen 1 , Sinan Khor 3 , Kesi Shi 1 , Zili He 1 , Jiawei Li 1 , Fanghua Gong 2 , Yanlong Liu 2 , Aiping Hu 2 , Jian Xiao 1, 2 and Xiangyang Wang 1 1 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China 2 Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China 3 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, U.S.A * These authors have contributed equally to this work Correspondence to: Jian Xiao, email: xfxj2000@126.com Xiangyang Wang, email: xiangyangwang@126.com Keyword: spinal cord injury, apoptosis, liraglutide, GLP-1R, autophagy Received: May 26, 2017 Accepted: July 13, 2017 Published: September 08, 2017 ABSTRACT Therapeutics used to treat central nervous system (CNS) injury are designed to promote axonal regeneration and inhibit cell death. Previous studies have shown that liraglutide exerts potent neuroprotective effects after brain injury. However, little is known if liraglutide treatment has neuroprotective effects after spinal cord injury (SCI). This study explores the neuroprotective effects of liraglutide and associated underlying mechanisms. Our results showed that liraglutide could improve recovery after injury by decreasing apoptosis as well as increasing microtubulin acetylation, and autophagy. Autophagy inhibition with 3-methyladenine (3-MA) partially reversed the preservation of spinal cord tissue and decreased microtubule acetylation and polymerization. Additionally, siRNA knockdown of GLP-1R suppressed autophagy and reversed mTOR inhibition induced by liraglutide in vitro , indicating that GLP-1R regulates autophagic flux. GLP-1R knockdown ameliorated the mTOR inhibition and autophagy induction seen with liraglutide treatment in PC12 cells under H 2 O 2 stimulation. Taken together, our study demonstrated that liraglutide could reduce apoptosis, improve functional recovery, and increase microtubule acetylation via autophagy stimulation after SCI. GLP-1R was associated with both the induction of autophagy and suppression of apoptosis in neuronal cultures.

Diabetic peripheral neuropathy (DPN) is one of the most common and troublesome complications of diabetes mellitus. It has been demonstrated that nerve growth factor (NGF) exerts a pivotal role in the regulation of neuronal growth and the promotion of DPN recovery. However, the exact molecular mechanisms are not well understood. Recent studies have indicated that as a novel therapeutic target, endoplasmic reticulum (ER) stress participates in the onset and progression of DPN. In the present study, it has been demonstrated that NGF prevents the sciatic nerve from degeneration and demyelination in DPN rats. Thus, RSC 96 cells, which retain the characteristic features of Schwann cells (SCs), were cultured in medium containing 30 mM glucose (high glucose, HG) to mimic SCs in DPN mice. The 50-ng/ml dose of NGF was identified to be the optimal concentration for treating an excessive ER stress level under HG conditions for 24 h. We found that NGF treatment significantly inhibits HG-induced ER stress and subsequently suppresses ER-related apoptosis. Further, NGF administration also activates the upstream signaling pathway of ER stress, PI3K/Akt/GSK3β signaling and ERK1/2 signaling. Co-treatment with the PI3K inhibitor LY294002 or ERK1/2 inhibitor U0126 significantly reverses the protective role of NGF on HG-induced excessive ER stress and subsequent apoptosis. These observations suggest that the neuroprotective role of NGF in DPN is mediated by the inhibition of excessive ER stress via the activation of the PI3K/Akt/GSK3β and ERK1/2 signaling pathways.

Since the 1990s, the development of art design education in China has entered a whole new period. With the development of the reform and opening up economy, the strong demand for art and design talents is reflected in network planning. New areas such as analog design and innovative animation development. This emerging demand has made the development of information art education an eruption period without the need to advocate for natural formation. This article is precisely in this era background, as a cutting-edge research on the development context and characteristics of information art design and the new development of art design education in the information age. Through the reading and research of related theories and literature, this article summarizes the connotation and context of the historical development of design basic education, and discusses the problems and characteristics of design education in the context of information design and information society. This article adopts the network information model, based on the new requirements of the basic teaching of art design of network information, and has made relevant adjustments to the previous courses. Not only should we take care of the content of the original curriculum arrangement, but also fully reflect the combination of basic courses and information technology. In the teaching of this article, the design philosophy and computer information technology are combined to design basic education content that can meet the requirements of the information age. It provides suggestions for the study of epoch-making intelligent art design courses.

At present, with the acceleration of urbanization and the strong embedding of foreign cultures, traditional urban culture faces serious threats and disintegration. Cultural faults have become a common problem in Chinese cities. As one of the four centrally administered municipalities in China, Chongqing has a history of two thousand years. In recent years, with the development of modernization, Chongqing’s original unique regional urban characteristics are gradually disappearing. This paper selects the most representative urban landscape of Chongqing as the research object. The purpose of this paper is to find out the phenomenon of cultural regeneration of Chongqing Bayu culture in modern landscape design, and to find out the method of cultural regeneration of traditional Bayu culture in modern landscape. In order to achieve this goal, this paper uses the research method of case investigation. First, select the landscape of the Three Gorges Square, which best represents the image of Chongqing city, for investigation. Then through the on-the-spot investigation, shooting records, conversation records and other forms, the investigation found out the phenomenon of the regeneration of Chongqing Bayu culture in the square landscape, and finally, by analyzing the phenomena appearing in the landscape of these Bayu cultures, the traditional methods of cultural regeneration in the modern landscape can be analyzed.

s Background: Type 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. Liver injury is one of these that severely affects patients with diabetes. Fibroblast growth factor 1 (FGF1) has glucose-lowering activity and plays a role in modulation of several liver injuries. Nevertheless, the effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown. Methods: To further investigate the effect of FGF1 on diabetic liver injury, we divided db/db mice into two groups and intraperitoneally (i.p.) injected either with FGF1 at 0.5 mg/kg body weight or saline every other day for 4 weeks. Then body weights were measured. Serum and liver tissues were collected for biochemical and molecular analyses. Results: FGF1 significantly reduced blood glucose and ameliorated diabetes-induced liver steatosis, fibrosis and apoptosis. FGF1 also restored defective hepatic autophagy in db/db mice. Mechanistic investigations showed that diabetes markedly induced oxidative stress and endoplasmic reticulum stress and that FGF1 treatment significantly attenuated these effects. Conclusions: FGF1-associated glucose level reduction and amelioration of cellular stress are potential protective effects of FGF1 against diabetes-induced liver injury. Key words: Fibroblast growth factor 1 (FGF1); Diabetes; Liver injury; Oxidative stress; Endoplasmic reticulum (ER) stress

Spinal cord injury (SCI) is a devastating neurological disorder that usually leads to a loss of motor and sensory function in patients. The expression of hypoxia inducible factor-1α (HIF-1α) is increased, and exerts a protective role after traumatic SCI. However, the endogenous activity of HIF-1α is insufficient for promoting functional recovery. The present study tested the potential effect of the sustained activation of HIF-1α by the prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) on anti-apoptotic process and the regulation of axonal regeneration after SCI. Here, we found that treatment with DMOG significantly increased the expression of HIF-1α and that the stabilization of HIF-1α induced by DMOG not only decreased the expression of apoptotic proteins to promote neural survival, but also enhanced axonal regeneration by regulating microtubule stabilization

In recent years, many studies have focused on autophagy, an evolutionarily conserved mechanism that relies on lysosomes to achieve cellular metabolic requirements and organelle turnover, and revealed its important role in animal models of traumatic injury. Autophagy is a double-edged sword. Appropriate levels of autophagy can promote the removal of abnormal proteins or damaged organelles, while hyperactivated autophagy can induce autophagic apoptosis. However, recent studies suggest that autophagic flux seems to be blocked after traumatic brain injury (TBI), which contributes to the apoptosis of brain cells. In this study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin & eosin staining and Nissl staining were first conducted to confirm that VPA treatment had a therapeutic effect on mice after TBI. Western blotting, enzyme-linked immunosorbent assay and immunofluorescence staining were then performed to reveal that VPA treatment reversed TBI-induced blockade of autophagic flux, which was accompanied by a reduced inflammatory response. In addition, the variations in activation and phenotypic polarization of microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3-methyladenine partially abolished VPA-induced neuroprotection and the regulation of microglial function after TBI, resulting in the deterioration of the central nervous system microenvironment and neurological function. Collectively, VPA treatment reversed the TBI-induced blockade of autophagic flux in the mouse brain cortex, subsequently inhibiting brain cell apoptosis and affecting microglial function to achieve the promotion of functional recovery in mice after TBI. Cover Image for this issue: doi: 10.1111/jnc.14755.

ObjectivesTo develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.DesignA nationally representative retrospective study.SettingRepresentative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.ParticipantsRepresentative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measuresIn-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).ResultsA total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.ConclusionsThe models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

Recently, the combination of plasmonic noble metallic nanostructures with semiconductors for plasmon-enhanced visible light-driven water splitting (WS) has attracted considerable attention. This review first presents three prime enhancement mechanisms for plasmon-enhanced photocatalytic WS, and then some state-of-the-art representative studies are introduced according to different enhancement mechanisms. Furthermore, the design parameters of plasmonic-metal/semiconductor photocatalysts are discussed in detail, focusing on the effect of shape, size and geometric position of metallic nanostructures on the photocatalytic activity of visible light-driven WS. Finally, the challenges and perspectives for plasmon-enhanced solar WS are proposed.

// Yongmin Li 1, * , Yanmei Yang 2, * , Jingwen Li 1, * , He Liu 1 , Fuxun Chen 2 , Bingyang Li 2 , Binbin Cui 1 , Yanlong Liu 1 1 Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China 2 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China * These authors contributed equally to this work Correspondence to: Binbin cui, email: cuibinbin222@hotmail.com Yanlong Liu, email: liuyanlong1979@163.com Keywords: USP22, liver metastasis, colorectal cancer, EMT, AP4 Received: October 12, 2016 Accepted: February 22, 2017 Published: March 06, 2017 ABSTRACT Ubiquitin specific peptidase 22 (USP22), a putative cancer stem cell marker, is overexpressed in liver metastases of colorectal cancer (CRC). However, the mechanism by which USP22 promotes CRC metastasis remains largely unknown. Here, we report that USP22 and AP4 are simultaneously overexpressed during TGF-β1-induced CRC cell epithelial-mesenchymal transition (EMT). USP22 up-regulation enhances CRC cell migration and invasion and EMT-related marker and AP4 expression, but these effects are partly blocked by AP4 knockdown. In addition, USP22 binds to the promoter region of AP4 to activate its transcription. In vivo , elevated USP22 expression promotes CRC cell metastasis to the lungs in nude mice, as evidenced by the fact that CRC metastatic nodules stain deeply positive for USP22 and AP4. In human CRC tissues, the genes encoding USP22 and AP4 are overexpressed in metastatic liver lesions compared with primary cancer tissues, and their overexpression is significantly associated with poor CRC patient survival. These findings indicate that USP22 and AP4 may serve as prognostic markers for predicting the risk of developing distant metastases in CRC.

The unique optical properties possessed by plasmonic noble metal nanostructures in consequence of localized surface plasmon resonance (LSPR) are useful in diverse applications like photovoltaics, sensing, non-linear optics, hydrogen generation, and photocatalytic pollutant degradation. The incorporation of plasmonic metal nanostructures into solar cells provides enhancement in light absorption and scattering cross-section (via LSPR), tunability of light absorption profile especially in the visible region of the solar spectrum, and more efficient charge carrier separation, hence maximizing the photovoltaic efficiency. This review discusses about the recent development of different plasmonic metal nanostructures, mainly based on Au or Ag, and their applications in promising third-generation solar cells such as dye-sensitized solar cells, quantum dot-based solar cells, and perovskite solar cells.

// Yulong Zhou 1, 2, * , Yanqing Wu 3, * , Yanlong Liu 2, * , Zili He 1, 2 , Shuang Zou 2 , Qingqing Wang 1, 2 , Jiawei Li 1, 2 , Zengming Zheng 1, 2 , Jian Chen 1, 2 , Fenzan Wu 4 , Fanhua Gong 3 , Hongyu Zhang 2 , Huazi Xu 1 , Jian Xiao 1, 2 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China 2 Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035 China 3 The Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China 4 Department of Neurosurgery, Affiliated Cixi People’s Hospital, Wenzhou Medical University, Ningbo, 315300, China * These authors have contribute equally to this work Correspondence to: Jian Xiao, email: xfxj2000@126.com Huazi Xu, email: spinexu@163.com Keywords: spinal cord injury (SCI), blood-spinal cord barrier (BSCB), endoplasmic reticulum (ER) stress, autophagy Received: October 05, 2016 Accepted: November 07, 2016 Published: December 02, 2016 ABSTRACT Spinal cord injury induces the disruption of blood-spinal cord barrier and triggers a complex array of tissue responses, including endoplasmic reticulum (ER) stress and autophagy. However, the roles of ER stress and autophagy in blood-spinal cord barrier disruption have not been discussed in acute spinal cord trauma. In the present study, we respectively detected the roles of ER stress and autophagy in blood-spinal cord barrier disruption after spinal cord injury. Besides, we also detected the cross-talking between autophagy and ER stress both in vivo and in vitro . ER stress inhibitor, 4-phenylbutyric acid, and autophagy inhibitor, chloroquine, were respectively or combinedly administrated in the model of acute spinal cord injury rats. At day 1 after spinal cord injury, blood-spinal cord barrier was disrupted and activation of ER stress and autophagy were involved in the rat model of trauma. Inhibition of ER stress by treating with 4-phenylbutyric acid decreased blood-spinal cord barrier permeability, prevented the loss of tight junction (TJ) proteins and reduced autophagy activation after spinal cord injury. On the contrary, inhibition of autophagy by treating with chloroquine exacerbated blood-spinal cord barrier permeability, promoted the loss of TJ proteins and enhanced ER stress after spinal cord injury. When 4-phenylbutyric acid and chloroquine were combinedly administrated in spinal cord injury rats, chloroquine abolished the blood-spinal cord barrier protective effect of 4-phenylbutyric acid by exacerbating ER stress after spinal cord injury, indicating that the cross-talking between autophagy and ER stress may play a central role on blood-spinal cord barrier integrity in acute spinal cord injury. The present study illustrates that ER stress induced by spinal cord injury plays a detrimental role on blood-spinal cord barrier integrity, on the contrary, autophagy induced by spinal cord injury plays a furthersome role in blood-spinal cord barrier integrity in acute spinal cord injury.

// Shulin Pan 1, * , Songlin Li 2, * , Yingying Hu 1 , Hao Zhang 1 , Yanlong Liu 3 , Huai Jiang 1 , Mingchu Fang 1 , Zhengmao Li 3 , Kebin Xu 3 , Hongyu Zhang 3 , Zhenlang Lin 1 , Jian Xiao 3 1 Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, China 2 The Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China 3 The School of Pharmacy, Wenzhou Medical University, Wenzhou 325035, China * These authors contribute equally to this work Correspondence to: Jian Xiao, email: xfxj2000@126.com Zhenlang Lin, email: linzhenlang@hotmail.com Keywords: resveratrol, hypoxia-ischemia, brain damage, inflammation, apoptosis Received: July 25, 2016 Accepted: October 19, 2016 Published: November 02, 2016 ABSTRACT Neonatal hypoxic-ischemic brain injury is a devastating disease with limited treatment options. Preventive treatment with resveratrol has indicated to be well tolerated and has lower toxicity in both experimental models and human patients. However, whether resveratrol administration post-hypoxic-ischemic protects against neonatal hypoxic-ischemic injury is not known. Here we reported that post-treatment with resveratrol significantly reduced brain damage at 7-day after the injury. We found that resveratrol reduced the expression levels of key inflammatory factors at the mRNA and protein levels, and at least partially via inhibiting microglia activation. Moreover, resveratrol exerted an anti-apoptotic effect, as assessed by TUNEL staining, and altered the expression of the apoptosis-related genes Bax, Bcl-2 and caspase3. Our data indicate that post-treatment with resveratrol protects against neonatal hypoxic-ischemic brain injury and suggest a promising therapeutic strategy to this disease.

An increase in the use of iodinated contrast media, such as iohexol, iodixanol, iopamidol and iopromide, occasionally causes contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). The present study aimed to assess the effects of low levels of hemoglobin on the development of CIN in patients with normal renal function following CAG/PCI. A total of 841 consecutive patients undergoing CAG/PCI were divided into two groups: Patients with low levels of hemoglobin (male

Host inflammation is a critical component of tumor progression and its status can be indicated by peripheral blood cell counts. We aimed to construct a comprehensively prognostic inflammatory index (PII) based on preoperative peripheral blood cell counts and further evaluate its prognostic value for patients with colorectal cancer (CRC). A total of 9315 patients with stage II and III CRC from training and external validation cohorts were included. The PII was constructed by integrating all the peripheral blood cell counts associated with prognosis in the training cohort. Cox analyses were performed to evaluate the association between PII and overall survival (OS) and disease-free survival (DFS). In the training cohort, multivariate Cox analyses indicated that high OS-PII (&gt, 4.27) was significantly associated with worse OS (HR: 1.330, 95% CI: 1.189&ndash, 1.489, p &lt, 0.001), and high DFS-PII (&gt, 4.47) was significantly associated with worse DFS (HR: 1.366, 95% CI: 1.206&ndash, 1.548, p &lt, 0.001). The prognostic values of both OS-PII and DFS-PII were validated in the external validation cohort. The nomograms achieved good accuracy in predicting both OS and DFS. Time-dependent ROC analyses showed that both OS-PII and DFS-PII have a stable prognostic performance at various follow-up times. The prognostic value of tumor-node-metastasis staging could be enhanced by combining it with either OS-PII or DFS-PII. We demonstrated that PIIs are independent prognostic predictors for CRC patients, and the nomograms based on PIIs can be recommended for personalized survival prediction of patients with CRC.

In the course of the development of Chinese history, the long history has made the traditional Chinese culture show nationality and rich connotation. Chinese elements, as one of the main signs and symbols of traditional Chinese culture, are an important part of the development of Chinese and world civilization. In the design of each part of the new rural landscape, regional cultural elements such as paper-cut shadows and Chinese calligraphy were used. Can greatly enhance the characteristics of Chinese culture. Therefore, the application of Chinese traditional cultural elements to the modern new rural landscape design is the main task faced by the new rural landscape designer. In the construction of theory and practice, this article discusses the development of the new countryside by using the Chinese element symbol and the concept method of the beautiful countryside, as a reference for the new rural landscape design. This paper obtains the proportion of the importance of the new rural landscape design principles, with inheritance and continuity accounting for 24%. This paper is mainly divided into the gaps that can fill Chinese rural cultural elements in the new rural landscape design. At the same time, I hope that more people who love culture can better understand the local culture and experience the new beautiful rural scenery. It is hoped that the results of this study will re-awaken people’s attention to regional culture.

Key Points Question Is cigarette smoking associated with changes in specific neurodegenerative biomarkers in cerebrospinal fluid? Findings In this case-control study of 191 adult men in China, active smoking was associated with at-risk biomarkers for Alzheimer disease, as indicated by higher β-amyloid 42 levels. Meaning The results of this study broaden our understanding of the association of cigarette smoking with neurodegenerative disorders., This case-control study investigates the association of cigarette smoking with cerebrospinal fluid biomarkers of neurodegeneration, neuroinflammation, oxidation, and neuroprotection., Importance Cigarette smoking has been associated with risk of neurodegenerative disorders, such as Alzheimer disease. The association between smoking and biomarkers of changes in human cerebrospinal fluid (CSF) is not fully understood. Objective To investigate the association of cigarette smoking with CSF biomarkers of neurodegeneration, neuroinflammation, oxidation, and neuroprotection. Design, Setting, and Participants In this case-control study of 191 adult men in China, biomarkers in the CSF of participants with and without significant cigarette exposure were examined. Participants who did not smoke and had no history of substance use disorder or dependence were assigned to the nonsmoking group. The active smoking group included participants who consumed at least 10 cigarettes per day for 1 year. Five-milliliter samples of CSF were obtained from routine lumbar puncture conducted before anterior cruciate ligament reconstruction surgery. Data collection took place from September 2014 to January 2016, and analysis took place from January to February 2016. Exposures Cigarette smoking. Main Outcomes and Measures CSF levels of β-amyloid 42 (Aβ42), which has diagnostic specificity for Alzheimer disease, tumor necrosis factor alpha (TNFα), brain-derived neurotrophic factor (BDNF), total superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured. Sociodemographic data and history of smoking were obtained. Results Of 191 participants, 87 (45.5%) were included in the active smoking group and 104 (54.4%) in the nonsmoking group. Compared with the active smoking group, the nonsmoking group was younger (mean [SD] age, 34.4 [10.5] years vs 29.6 [9.5] years; P = .01), had more education (mean [SD] duration of education, 11.9 [3.1] years vs 13.2 [2.6] years; P = .001), and had lower body mass index (mean [SD], 25.9 [3.6] vs 24.9 [4.0]; P = .005). Comparing the nonsmoking group with the smoking group, mean (SD) CSF levels of Aβ42 (38.0 [25.9] pg/mL vs 52.8 [16.5] pg/mL; P

Application value of epidural anesthesia combined with epidural analgesia and general anesthesia combined with intravenous analgesia in ovarian cancer surgery was explored. In total 298 ASA I-III grade patients with ovarian cancer, undergoing extensive total hysterectomy and pelvic lymphotomy, were retrospectively analyzed. Patients were divided into two groups: the epidural anesthesia combined with epidural analgesia group (group A, 158 cases), and the general anesthesia combined with intravenous analgesia group (group B, 140 cases). The first exhaust time, incidence of adverse reactions, Aldrete score, and recovery were observed, and the visual analogue scale (VAS) scores during resting, exercise and cough at 24 h after surgery were recorded. Fasting venous blood (2 ml) was drawn at the same time before anesthesia and at 24 h after anesthesia in both groups to determinate cortisol (COR) and C-reactive protein (CRP) levels. The first exhaust time and incidence of adverse reactions in group A were significantly lower than those in group B (P

Glutamate is involved in mental disorders and nicotine addiction. The aim of the present study was to evaluate the relationship between cerebrospinal fluid (CSF) glutamate levels and mental status in Chinese heavy smokers. Participants comprised 41 non-smokers and 77 heavy smokers (n = 118). Cerebrospinal fluid was extracted and glutamate levels were measured. We recorded age, years of education, BMI, the Barratt impulsiveness scale (BIS), the Beck Depression Inventory (BDI) and the Self-Rating Anxiety Scale (SAS). BIS action scores, total scores and BDI scores were significantly different between the groups. Partial correlation analyses with age and education years as covariates found that CSF glutamate levels negatively correlated with BDI scores, but did not correlate with SAS scores in heavy smokers. No correlation was found between CSF glutamate levels and BDI or SAS scores in non-smokers. In conclusion, heavy smokers had more impulsivity had lower levels of CSF glutamate and higher BDI scores. CSF glutamate levels negatively correlated with BDI scores in heavy smokers.

Overweight individuals are at higher risk for developing type II diabetes than the general population. We conducted this study to analyze the correlation between blood glucose and biochemical parameters, and developed a blood glucose prediction model tailored to overweight patients.A total of 346 overweight Chinese people patients ages 18-81 years were involved in this study. Their levels of fasting glucose (fs-GLU), blood lipids, and hepatic and renal functions were measured and analyzed by multiple linear regression (MLR). Based the MLR results, we developed a back propagation artificial neural network (BP-ANN) model by selecting tansig as the transfer function of the hidden layers nodes, and purelin for the output layer nodes, with training goal of 0.5×10(-5).There was significant correlation between fs-GLU with age, BMI, and blood biochemical indexes (P0.05). The results of MLR analysis indicated that age, fasting alanine transaminase (fs-ALT), blood urea nitrogen (fs-BUN), total protein (fs-TP), uric acid (fs-BUN), and BMI are 6 independent variables related to fs-GLU. Based on these parameters, the BP-ANN model was performed well and reached high prediction accuracy when training 1 000 epoch (R=0.9987).The level of fs-GLU was predictable using the proposed BP-ANN model based on 6 related parameters (age, fs-ALT, fs-BUN, fs-TP, fs-UA and BMI) in overweight patients.

// Gui-Qian Huang 1, 2, * , Gui-Qi Zhu 1, 3, * , Yan-Long Liu 4, * , Li-Ren Wang 1, 3 , Martin Braddock 5 , Ming-Hua Zheng 1, 6 , Meng-Tao Zhou 7 1 Department of Infection and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China 2 Renji School of Wenzhou Medical University, Wenzhou 325000, China 3 School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou 325000, China 4 College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China 5 Global Medicines Development, AstraZeneca R&D, Alderley Park, United Kingdom 6 Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China 7 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China * Co-first author Correspondence to: Ming-Hua Zheng, e-mail: zhengmh@wmu.edu.cn Meng-Tao Zhou, e-mail: zmt0417@hotmail.com Keywords: neutrophil-to-lymphocyte ratio, hepatocellular carcinoma, curative liver resection, overall survival Received: November 23, 2015 Accepted: December 14, 2015 Published: December 21, 2015 ABSTRACT Objectives: Neutrophil lymphocyte ratio (NLR) has been shown to predict prognosis of cancers in several studies. This study was designed to evaluate the impact of stratified NLR in patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods: A total of 1659 patients who underwent CLR for suspected HCC between 2007 and 2014 were reviewed. The preoperative NLR was categorized into quartiles based on the quantity of the study population and the distribution of NLR. Hazard ratios (HRs) and 95% confidence intervals (CIs) were significantly associated with overall survival (OS) and derived by Cox proportional hazard regression analyses. Univariate and multivariate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis. Results: Multivariable Cox proportional hazards models showed that the level of NLR (HR = 1.031, 95%CI: 1.002-1.060, P = 0.033), number of nodules (HR = 1.679, 95%CI: 1.285-2.194, P

Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced liver injury and exogenous FGF21 administration protected liver from chronic alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild time (WT) control mice were divided into two groups and fasted for 24 hours followed by a bonus of alcohol treatment at a dose of 5 g/kg body weight via gavage. Serum alcohol concentration was measured after gavage at 0.5, 2, 3, 4 and 6 hours, respectively. At the end, gastric and liver tissues were collected. Serum alcohol concentration of KO mice was significantly lower than that of WT at 0.5 hours after alcohol expose. There were no significant differences in alcohol dehydrogenase (ADH) activity and aldehyde dehydrogenase 2 (ALDH2) activity in gastric and liver tissues between WT and the KO mice. However, gastric emptying time of KO mice was much longer than that of WT mice. In addition, the intestinal permeability and serum GLP-1 level of KO mice were significantly higher than that of WT mice. These results suggest that FGF21 deficiency slow gastric emptying rate and indirectly influence initial alcohol metabolism in mice exposed to acute alcohol. Our findings provide additional information for understanding the gastrointestinal mechanism of alcoholic liver disease and other alcohol use disorders.