[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Hydroxyfasudil regulates immune balance and suppresses inflammatory responses in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a central nervous system (CNS) disease with complicated etiology. Multifocal demyelination and invasion of inflammatory cells are its primary pathological features. Fasudil has been confirmed to improve experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, Fasudil is accompanied by several shortcomings in the clinical practice. Hydroxyfasudil is a metabolite of Fasudil in the body with better pharmaceutical properties. Therefore, we attempted to study the influence of Hydroxyfasudil upon EAE mice. The results demonstrated that Hydroxyfasudil relieved the symptoms of EAE and the associated pathological damage, reduced the adhesion molecules and chemokines, decreased the invasion of peripheral immune cells. Simultaneously, Hydroxyfasudil modified the rebalance of peripheral T cells. Moreover, Hydroxyfasudil shifted the M1 phenotype to M2 polarization, inhibited inflammatory signaling cascades as well as inflammatory factors, and promoted anti-inflammatory factors in the CNS. In the end, mice in the Hydroxyfasudil group expressed more tight junction proteins, indirectly indicating that the blood-brain barrier (BBB) was protected. Our results indicate that Hydroxyfasudil may be a prospective treatment for MS.

Systemic evaluation of lymphocyte-bound C4d and immunoglobulins for diagnosis and activity monitoring of systemic lupus erythematosus.

OBJECTIVE: To investigate the role of lymphocyte-bound C4d (LB-C4d: T-C4d, B-C4d) and immunoglobulins (LB-Igs: T-IgG, T-IgM, B-κ and B-λ) in the diagnosis and monitoring of SLE. DESIGN & METHODS: The levels of C4d and Igs on peripheral lymphocytes were measured in 172 patients with SLE, 174 patients with other non-SLE inflammatory diseases and 100 healthy individuals. Immunobinding and blocking experiments were performed to characterize Igs from SLE patients to generate LB-C4d/Igs in vitro. Sixty-five patients with SLE were followed up longitudinally. Disease activity was assessed for each SLE patient. RESULTS: Patients with SLE had the highest median LB-C4d/Igs levels. LB-C4d had a significant but weak positive association with LB-Igs, with correlation coefficients ranging from 0.008 to 0.316. Anti-cardiolipin IgG and anti-ß2GP1 IgG, but not C3 and C4, were found to be closely associated with LB-C4d/Igs formation, with correlations as high as 0.337. Compared to anti-dsDNA, LB-C4d performed better in SLE diagnosis, while B-κ and B-λ performed better in disease activity monitoring. CONCLUSIONS: Both autoantibodies and receptors on lymphocytes contribute to LB-C4d/Igs formation. LB-C4d/Igs could be used as reliable indicators for SLE diagnosis and activity monitoring.

Best treatment options for occult breast cancer: A meta-analysis.

Objectives: Occult breast cancer (OBC) is a rare malignant breast tumor. Because of the rare cases and limited clinical experience, a huge therapeutic difference has existed all over the world and standardized treatments have yet been established. Methods: A meta-analysis was conducted using MEDLINE and Embase databases to identify the choice of OBC surgical procedures in all studies: (1) patients undergoing axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) only; (2) patients undergoing ALND with radiotherapy (RT); (3) patients undergoing ALND with breast surgery (BS); (4) patients undergoing ALND with RT and BS; and (5) patients undergoing observation or RT only. The primary endpoints were mortality rates, the second endpoints were distant metastasis and locoregional recurrence. Results: Among the 3,476 patients, 493 (14.2%) undergo ALND or SLNB only; 632 (18.2%) undergo ALND with RT; 1483 (42.7%) undergo ALND with BS; 467 (13.4%) undergo ALND RT and BS, and 401 (11.5%) undergo observation or RT only. After comparing the multiple groups, both groups 1 and 3 have higher mortality rates than group 4 (30.7% vs. 18.6%, p < 0.0001; 25.1% vs. 18.6%, p = 0.007), and group 1 has higher mortality rates than groups 2 and 3 (30.7% vs.14.7%, p < 0.00001; 30.7 vs. 19.4%, p < 0.0001). Group (1 + 3) had a prognosis advantage over group 5 (21.4% vs. 31.0%, p < 0.00001). There was no significant difference both in the distant recurrence rates and locoregional rates between group (1 + 3) and group (2 + 4) (21.0% vs. 9.7%, p = 0.06; 12.3% vs. 6.5%, p = 0.26). Conclusion: On the basis of this meta-analysis, our study indicates that BS including modified radical mastectomy (MRM) and breast-conserving surgery (BCS) combined RT may appear as the optimal surgical approach in patients with OBC. RT cannot prolong both the time of distant metastasis and the local recurrences.

Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats.

PURPOSE: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). METHODS: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. RESULTS: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. CONCLUSIONS: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.

The double-edged sword effects of active social media use on loneliness: The roles of interpersonal satisfaction and fear of missing out.

Introduction: Social media' impact on loneliness has attracted widespread scholarly attention. One hypothesis is that active social media use (ASMU) is associated with a decrease in loneliness. However, several empirical studies did not find a significant correlation between ASMU and loneliness, and ASMU may even increase loneliness. This study explored the mechanism of the double-edged sword effects of ASMU on loneliness. Methods: Data were collected through convenience sampling from three universities in China. A total of 454 Chinese college social media users (Mean age 19.75 ± 1.33; 59.92% female) completed an online questionnaire. Results: ASMU was positively related to interpersonal relationship satisfaction, which was negatively related to general trait-fear of missing out (FoMO) and loneliness. Further structural equation modeling (SEM) analysis showed that ASMU could negatively predict loneliness through the mediation pathways of interpersonal satisfaction and "Interpersonal satisfaction → Trait-FoMO." At the same time, ASMU was also positively associated with online-specific state-FoMO, which was positively associated with trait-FoMO and loneliness. Further SEM analysis found no mediation effect of state-FoMO between ASMU and loneliness, but state-FoMO and traitFoMO sequentially mediate the relationship between ASMU and loneliness. Discussion: This study indicates that ASMU may increase and decrease loneliness. Interpersonal satisfaction and FoMO explained the double-edged mechanism of ASMU on loneliness. These findings contribute to dialectically understanding the effectiveness of active social media use and provide theoretical guidance for promoting the beneficial aspects of social media while weakening its harmful consequences.

Prognostic and predictive significance of serum soluble scavenger receptor A in acute primary basal ganglia hemorrhage: A prospective cohort study.

BACKGROUND: Scavenger receptor A (SRA) can regulate immune response and is involved in pathophysiological processes of acute brain injury. We analyzed the prognostic role of serum soluble SRA in intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study of 110 healthy controls and 110 patients with acute basal ganglia hemorrhage, serum soluble SRA concentrations were detected. Univariate analyses, followed by multivariate logistic regression analyses, were utilized to explore the relationship between serum soluble SRA concentrations and early neurologic deterioration (END) plus post-stroke 3-month poor prognosis (modified Rankin Scale scores of 3-6). RESULTS: Serum soluble SRA concentrations of patients were significantly higher than those of controls (median, 3.6 vs 0.9 ng/ml; P < 0.001). Serum soluble SRA concentrations of patients were independently correlated with hematoma volume (ß, 0.201; 95 % confidence interval (CI), 0.093-0.309; P = 0.001), National Institutes of Health Stroke Scale (NIHSS) scores (ß, 0.118; 95 % CI, 0.024-0.213; P = 0.024), and 3-month modified Rankin Scale scores (ß, 0.148; 95 % CI, 0.063-0.232; P = 0.001). Serum soluble SRA concentrations independently predicted END and poor 3-month prognosis with odds ratio values of 1.394 (95 % CI, 1.024-1.899; P = 0.035) and 1.441 (95 % CI, 1.016-2.044; P = 0.040) respectively. Serum soluble SRA concentrations were efficiently predictive of the development of END (ROC AUC 0.746; 95 % CI, 0.631-0.861) and poor 3-month prognosis (AUC, 0.773; 95 % CI, 0.685-0.861). Serum soluble SRA concentrations significantly improved AUCs of NIHSS score and hematoma volume to 0.889 (95 % CI, 0.829-0.948; P = 0.035) and 0.873 (95 % CI, 0.811-0.936; P = 0.036) for prognostic prediction. The END predictive ability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.900; 95 % CI, 0.835-0.965) was significantly superior to those of NIHSS score (P = 0.020) and hematoma volume (P = 0.022). The prognostic predictive capability of serum sSRA concentrations combined with NIHSS score and ICH volume (AUC, 0.907; 95 % CI, 0.852-0.962) substantially exceeded those of NIHSS score (P = 0.009) and hematoma volume (P = 0.005). CONCLUSIONS: Serum soluble SRA concentrations may reflect illness severity and neurologic function after ICH, indicating serum soluble SRA may serve as a promising prognostic biochemical marker of ICH.

Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats

Purpose: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). Methods: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. Results: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. Conclusion: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.

High Serum S100A12 Levels Predict Poor Outcome After Acute Primary Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) triggers an inflammatory cascade that damages brain tissues and worsens functional outcome. S100A12 functions to promote brain inflammation. We aimed to investigate the relationship between serum S100A12 levels and functional outcome in ICH patients. METHODS: Serum S100A12 levels were measured in 101 ICH patients hospitalized within 24 h after symptom onset. Poor functional outcome was defined as a modified Rankin scale of 3 or greater at 3 months after stroke. Early neurologic deterioration was defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) score or death at 24 hours from symptoms onset. RESULTS: High serum S100A12 levels were independently correlated with NIHSS score (t = 5.384, P < 0.001), hematoma volume (t = 4.221, P < 0.001) and serum C-reactive protein levels (t = 5.068, P < 0.001). Serum S100A12 levels were substantially higher in patients with a poor outcome (median, 66.5 versus 37.7 ng/mL; P < 0.001) or early neurological deterioration (median, 76.5 versus 40.1 ng/mL; P < 0.001) than in the other remainders, independently predicted a poor outcome (odds ratio, 1.035; 95% confidence interval, 1.007-1.064; P = 0.015) and early neurologic deterioration (odds ratio,1.032; 95% confidence interval, 1.003-1.060; P = 0.027), and significantly discriminated a poor outcome (area under curve, 0.794; 95% confidence interval, 0.702-0.868) and early neurologic deterioration (area under curve, 0.760; 95% confidence interval, 0.664-0.839) under receiver operating characteristic curve. CONCLUSION: High serum S100A12 levels at admission are highly associated with the extent of inflammatory response, severity, a poor functional outcome and early neurologic deterioration in ICH patients, substantializing serum S100A12 as a promising prognostic biomarker for ICH.

Ethyl Pyruvate-Derived Transdifferentiation of Astrocytes to Oligodendrogenesis in Cuprizone-Induced Demyelinating Model.

Astrocytes redifferentiate into oligodendrogenesis, raising the possibility that astrocytes may be a potential target in the treatment of adult demyelinated lesion. Upon the basis of the improvement of behavior abnormality and demyelination by ethyl pyruvate (EP) treatment, we further explored whether EP affects the function of astrocytes, especially the transdifferentiation of astrocytes into oligodendrogenesis. The results showed that EP treatment increased the accumulation of astrocytes in myelin sheath and promoted the phagocytosis of myelin debris by astrocytes in vivo and in vitro. At the same time, EP treatment induced astrocytes to upregulate the expression of CNTF and BDNF in the corpus callosum and striatum as well as cultured astrocytes, accompanied by increased expression of nestin, Sox2, and ß-catenin and decreased expression of Notch1 by astrocytes. As a result, EP treatment effectively promoted the generation of NG2+ and PDGF-Ra+ oligodendrocyte precursor cells (OPCs) that, in part, express astrocyte marker GFAP. Further confirmation was performed by intracerebral injection of primary astrocytes labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE). As expected, NG2+ OPCs expressing CFSE and Sox2 were elevated in the corpus callosum of mice treated with EP following transplantation, revealing that EP can convert astrocytes into myelinating cells. Our results indicate the possibility that EP lead to effective myelin repair in patients suffering from myelination deficit.Graphical Abstract The diagram of EP action for promoting myelin regeneration in CPZ model. EP promoted migration and enrichment of astrocytes to demyelinated tissue and induced astrocytes to express neurotrophic CNTF and BDNF as well as translation factor nestin, Sox2, and ß-catenin, which should contribute to astrocytes to differentiate of oligodendrogenesis. At the same time, EP promoted astrocytes to phagocytized myelin debris for removing the harmful substances of myelin regeneration.

Overexpression of Spondin-2 Is Associated with Recurrence-Free Survival in Patients with Localized Clear Cell Renal Cell Carcinoma.

BACKGROUND: The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear. METHODS: SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration in vitro were investigated. RESULTS: SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all P < 0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration in vitro. CONCLUSION: SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.

Prognostic value of admission serum glucose-phosphate ratio in predicting the 6-month outcome of patients with severe traumatic brain injury: A retrospective study.

BACKGROUND: Serum glucose-phosphate ratio has been revealed to be associated with severity and prognosis of aneurysmal subarachnoid hemorrhage. Objective of this study was to investigate the relationship between serum glucose-phosphate ratio and severe traumatic brain injury outcome. METHODS: Patients with severe traumatic brain injury were stratified in quartiles according to their serum glucose-phosphate ratio. Outcome parameters included mortality, overall survival and poor outcome defined as Glasgow outcome scale score of 1-3 at post-traumatic 6 months. Multiple logistic regression analysis was performed to evaluate the association between quartiles of serum glucose-phosphate ratio and outcome. RESULTS: Data from 105 patients were retrospectively reviewed. Glasgow coma scale score declined, Glasgow outcome scale score decreased, Rotterdam computed tomography classification were raised, mortality increased, overall survival probability reduced and percentage of poor outcome rose significantly with each quartile of serum glucose-phosphate ratio. After adjusting for other confounding factors, serum glucose-phosphate ratio according to quartiles was substantially related to 6-month mortality, overall survival and poor outcome. Under receiver operating characteristic curve, serum glucose-phosphate ratio showed a significantly high prognostic predictive capability. CONCLUSIONS: Serum glucose-phosphate ratio might be a potential variable that can reflect trauma severity and prognosis in patients with severe traumatic brain injury.

Clinical manifestations and risk factors of adenovirus respiratory infection in hospitalized children in Guangzhou, China during the 2011-2014 period.

To evaluate epidemiology and risk factors of severe adenovirus respiratory infection in hospitalized children in Guangzhou, China.A retrospective review study was conducted, and 542 children hospitalized for adenovirus respiratory infection, were included from January 2011 to December 2014. Patients were younger than 14 years. Disease severity was classified into severe and mild. Laboratory tests and clinical characteristics were analyzed for risk factors of adenovirus respiratory infection by multivariable logistic regression.Among these 542 children, 92.1% were aged < 6 years. Clinical diagnoses were upper respiratory infections in 11.6%, bronchiolitis in 16%, and mild pneumonia in 62.0% of children. Severe pneumonia rate was 10.3% (56/542) with a mortality rate of 0.9% (5/542). The cohort comprised 542 patients; 486 patients with mild adenovirus respiratory infection and 56 patients with severe adenovirus respiratory infection. Multivariable logistic regression was used to confirm associations between variables and adenovirus respiratory infection, after age and gender adjustment. Hospital stay, still significantly associated with adenovirus respiratory infection. Patients with longer hospital stay (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.13-1.28, P < .001), lower LYMPH (OR = 0.73 95% CI: 0.55-0.99, P = .039), and increased LDH (OR = 1.002, 95% CI: 1.001-1.003, P =  .001) had a higher risk of severe adenovirus respiratory infection.Adenovirus is a major pathogen in hospitalized children with respiratory infection. High serum LDH level and low lymphocyte count could be used as predictors of adenovirus respiratory infection severity in children.

Associations between dietary patterns and 10-year cardiovascular disease risk score levels among Chinese coal miners--a cross-sectional study.

BACKGROUND: Diet-related cardiovascular diseases have produced a large health burden in China. Coal miners are a high-risk population for cardiovascular disease, but there is little evidence concerning associations between coal miners' dietary patterns and their 10-year cardiovascular disease risk score levels. METHODS: The study included 2632 participants and focused on dietary patterns associated with higher 10-year cardiovascular disease risk score levels. A valid semi-quantitative food frequency questionnaire was used to collect data regarding dietary intake, and dietary patterns were identified using factor analysis combined with cluster analysis. Logistic regression was used to assess associations between dietary patterns and 10-year cardiovascular disease risk score levels. RESULTS: For ground workers, compared with the 'Healthy' pattern, the 'High-salt' and 'Refined grains' patterns were significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.50, 95% CI: 1.02-2.21; OR: 1.92, 95% CI: 1.26-2.93) and 10-year ischemic cardiovascular disease risk score level (OR: 2.18, 95% CI: 1.25-3.80; OR: 2.64, 95% CI: 1.48-4.72) adjusted for gender, and behavioural and socioeconomic factors. The 'High-fat and salt' pattern was significantly associated with higher 10-year ischemic cardiovascular disease risk score level (OR: 1.97, 95% CI: 1.13-3.42). For underground workers, the 'High-salt' pattern was significantly associated with higher 10-year atherosclerotic cardiovascular disease risk score level (OR: 1.65, 95% CI: 1.16-2.36) and 10-year ischemic cardiovascular disease risk score level (OR: 1.76, 95% CI: 1.09-2.84). CONCLUSIONS: This study provides evidence for dietary patterns associated with higher 10-year cardiovascular disease risk score levels in Chinese miners, and facilitates relevant departments in designing effective dietary guidelines to ameliorate dietary structures.

Determination of serum tissue kallikrein levels after traumatic brain injury.

BACKGROUND: Tissue kallikrein (TK) plays an important role in the kallikrein-kinin system. Its protective role has been demonstrated in traumatic brain injury (TBI). We attempted to determine relationship between serum TK levels and trauma severity in addition to clinical outcome in TBI. METHODS: We recruited 112 patients with severe TBI (Glasgow coma scale score < 9) and 112 controls. We configured 2 multivariate models to assess the relationship between serum TK levels and 30-day death. Its prognostic predictive ability was analyzed under receiver operating characteristic curve. RESULTS: TK levels were significantly lower in patients than in controls (median 0.148 mg/l, the upper - lower quartiles 0.121-0.185 vs. median 0.258 mg/l, the upper - lower quartiles 0.207-0.342, P < 0.001). TK levels were closely and positively correlated with Glasgow coma scale score (r = 0.550). TK levels <0.148 mg/l independently predicted 30-day mortality with odds ratio value of 4.752 (95% confidence interval (CI), 1.166-19.367) and 30-day overall survival with hazard ratio value of 3.698 (95% CI, 1.026-13.333). TK levels significantly discriminated 30-day mortality with area under curve of 0.822 (95% CI, 0.738-0.887). CONCLUSIONS: Serum TK can represent a potential predictor of clinical outcome in TBI patients.

Overexpression of COL5A1 promotes tumor progression and metastasis and correlates with poor survival of patients with clear cell renal cell carcinoma.

BACKGROUND AND AIMS: COL5A1 has been identified to be involved in metastasis of clear cell renal cell carcinoma (ccRCC) by bioinformatic analysis. This study aimed to investigate COL5A1 expression and its clinical significance in ccRCC. The function of COL5A1 in ccRCC was further investigated. METHODS: COL5A1 expression was examined in 256 ccRCC tissues and paired adjacent normal renal tissues by immunohistochemistry and real-time quantitative PCR. The clinical significance of COL5A1 expression was evaluated. Downregulation of COL5A1 was achieved using siRNA. The effects of COL5A1 silencing on cell proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo were investigated. RESULTS: COL5A1 expression was upregulated in the majority of the ccRCC tissues at both protein and mRNA levels. COL5A1 expression was significantly correlated with tumor diameter, tumor stage, tumor grade, distant metastasis, recurrence, necrosis, and sarcomatoid (all P<0.05). COL5A1 expression was also significantly associated with overall survival of ccRCC patients (HR 1.876; P=0.027) and recurrence-free survival of localized ccRCC patients (HR 4.751; P<0.001). The accuracy of TNM, University of California Los Angeles Integrated Staging System, and Mayo clinic stage, size, grade, and necrosis prognostic models was improved when COL5A1 expression was added. CONCLUSION: COL5A1 knockdown significantly inhibited cell proliferation, induced cell apoptosis, inhibited cell migration and invasion in vitro, and inhibited tumor growth in vivo. Therefore, COL5A1 may be a novel prognostic biomarker and a promising therapeutic target for ccRCC.

Sleep quality mediating the association of personality traits and quality of life among underground workers and surface workers of Chinese coal mine: A multi-group SEM with latent response variable mediation analysis.

The aim of this study was to examine whether the association between personality traits and quality of life (QOL) was mediated by sleep quality in coal miners and to explore whether the relationship between surface workers and underground workers was different. The cross-sectional study including 3090 coal mine workers aged 20 to 65 years from Shanxi province of China was conducted. Personality traits, QOL and sleep quality were respectively assessed using Eysenck Personality Questionnaire-Revised Short Scale for Chinese, World Health Organization Quality of Life-BREF, and sleep status questionnaire. The multi-group SEM with latent response variable method was conducted to evaluate the association between personality traits and QOL mediated by sleep quality. The difference of indirect effects between two subgroups was examined by Wald chi-square test. For surface workers, underground workers and overall sample, passive personality traits had a negative impact on QOL through poor sleep quality, whereas the active personality traits acted the opposite. However, the difference of indirect effect between two subgroups was not statistically significant. These results indicated that sleep quality may act as a partial mediator in the relationship between personality traits and QOL, and the relationship may not be affected by working environment.

High Strength and Deformation Mechanisms of Al0.3CoCrFeNi High-Entropy Alloy Thin Films Fabricated by Magnetron Sputtering.

Recently, high-entropy alloy thin films (HEATFs) with nanocrystalline structures and high hardness were developed by magnetron sputtering technique and have exciting potential to make small structure devices and precision instruments with sizes ranging from nanometers to micrometers. However, the strength and deformation mechanisms are still unclear. In this work, nanocrystalline Al0.3CoCrFeNi HEATFs with a thickness of ~4 µm were prepared. The microstructures of the thin films were comprehensively characterized, and the mechanical properties were systematically studied. It was found that the thin film was smooth, with a roughness of less than 5 nm. The chemical composition of the high entropy alloy thin film was homogeneous with a main single face-centered cubic (FCC) structure. Furthermore, it was observed that the hardness and the yield strength of the high-entropy alloy thin film was about three times that of the bulk samples, and the plastic deformation was inhomogeneous. Our results could provide an in-depth understanding of the mechanics and deformation mechanism for future design of nanocrystalline HEATFs with desired properties.

Serum Extracellular Superoxide Dismutase Is Associated with Diabetic Retinopathy Stage in Chinese Patients with Type 2 Diabetes Mellitus.

Extracellular superoxide dismutase (ecSOD) is the major extracellular scavenger of reactive oxygen species and associated with the diabetic complication in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the serum ecSOD activity in Chinese patients with different stages of diabetic retinopathy (DR) and evaluate the association between the serum ecSOD activity and the severity of DR. A total of 343 T2DM patients were categorized into three groups: nondiabetic retinopathy (NDR) group, nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Serum ecSOD activities were measured by the autoxidation of the pyrogallol method. In this study, 271, 46, and 26 patients were enrolled in the NDR, NPDR, and PDR groups, respectively. We found a significantly decreased trend of serum ecSOD activity among NDR subjects (118.0 ± 11.5 U/mL) compared to NPDR subjects (108.5 ± 11.9 U/mL) (P < 0.001) and NPDR subjects compared to PDR subjects (102.7 ± 12.4 U/mL) (P = 0.041). Serum ecSOD activity was an independent risk factor for DR (OR = 0.920, P < 0.001) and was associated with the progression of DR. Serum ecSOD activity might be a biomarker for DR screening and evaluation of the clinical severity of DR in Chinese T2DM patients.

Salinity Effects on Strategies of Glycogen Utilization in Livers of Euryhaline Milkfish (Chanos chanos) under Hypothermal Stress.

The fluctuation of temperature affects many physiological responses in ectothermic organisms, including feed intake, growth, reproduction, and behavior. Changes in environmental temperatures affect the acquisition of energy, whereas hepatic glycogen plays a central role in energy supply for the homeostasis of the entire body. Glycogen phosphorylase (GP), which catalyzes the rate-limiting step in glycogenolysis, is also an indicator of environmental stress. Here, we examined the effects of salinity on glycogen metabolism in milkfish livers under cold stress. A reduction of feed intake was observed in both freshwater (FW) and seawater (SW) milkfish under cold adaptation. At normal temperature (28°C), compared to the FW milkfish, the SW milkfish exhibited greater mRNA abundance of the liver isoform of GP (Ccpygl), higher GP activity, and less glycogen content in the livers. Upon hypothermal (18°C) stress, hepatic Ccpygl mRNA expression of FW milkfish surged at 3 h, declined at 6 and 12 h, increased again at 24 h, and increased significantly after 96 h. Increases in GP protein, GP activity, and the phosphorylation state and the breakdown of glycogen were also found in FW milkfish livers after 12 h of exposure at 18°C. Conversely, the Ccpygl transcript levels in SW milkfish were downregulated after 1 h of exposure at 18°C, whereas the protein abundance of GP, GP activity, and glycogen content were not significantly altered. Taken together, under 18°C cold stress, FW milkfish exhibited an acute response with the breakdown of hepatic glycogen for maintaining energy homeostasis of the entire body, whereas no change was observed in the hepatic glycogen content and GP activity of SW milkfish because of their greater tolerance to cold conditions.