Abstract Objective To explore the value of serum Dickkopf-3 (sDKK3) in predicting Early Neurological Deterioration (END) and in-hospital adverse outcomes in acute ischemic stroke (AIS) patients. Methods AIS patients (n = 200) were included and assessed by the National Institutes of Health Stroke Rating Scale. Serum Dkk3 levels were assessed by ELISA. END was defined as an increase of ≥ 4 points in NIHSS score within 72h. The biological threshold of sDKK3 level and END occurrence were predicted based on X-tile software. Primary outcomes were END and all-cause death, and the secondary outcome was ICU admission during hospitalization. The logistic regression model and Cox risk regression model were applied to evaluate the relationship between DKK3 level and END incidence, all-cause in-hospital mortality, and in-hospital adverse outcomes (ICU admission). Results During hospitalization, the incidence of END in patients with AIS was 13.0 %, and the mortality rate within 7 days after END was 11.54 % (3/26). In patients below the serum DKK3 cutoff (93.0 pg/mL), the incidence of END was 43.5 % (20/48). Patients with lower sDKK3 levels were associated with a 1.188-fold increased risk of developing END (OR = 1.188, 95 % CI 1.055‒1.369, p < 0.0001). However, there was no significant association with admission to the ICU. sDKK3 below the threshold (93.0 pg/mL) was a risk factor for death. Conclusion Predictive threshold levels of serum DKK3 based on X-tile software may be a potential predictive biomarker of in-hospital END in patients with AIS, and low levels of DKK3 are independently associated with increased in-hospital mortality. Dickkopf3 Dickkopf 3 Dickkopf- sDKK (sDKK3 (END inhospital hospital (AIS n 200 Scale Dkk ELISA 72h h Xtile X tile allcause all cause death hospitalization DKK admission. . admission) 130 13 0 13. 1154 11 54 11.5 3/26. 326 3/26 26 (3/26) 93.0 930 93 (93. pg/mL, pgmL pg/mL , pg mL 435 43 5 43. 20/48. 2048 20/48 20 48 (20/48) 1.188fold 1188fold fold 1.188 1 188 OR 1188 9 10551369 055 369 1.055‒1.369 0.0001. 00001 0.0001 0001 0.0001) However (sDKK 115 11. 32 3/2 2 (3/26 93. (93 204 20/4 (20/48 188fold 1.18 18 118 1055136 05 36 1.055‒1.36 0000 0.000 000 3/ (3/2 (9 20/ (20/4 1.1 105513 1.055‒1.3 0.00 00 (3/ ( (20/ 1. 10551 1.055‒1. 0.0 (3 (20 1055 1.055‒1 0. (2 105 1.055‒ 10 1.055 1.05 1.0

Abstract In this study, the synergistic effects of jujube polysaccharide (JP) and flavonoid (JF) on aging mice were investigated. Sub-acutely aging mouse models were established using D-galactose. Eighty experimental mice were randomly assigned to normal, model, vitamin C (200 mg/kg), JP (200 mg/kg), JF (200 mg/kg) and JP + JF (low (100 mg/kg), medium (200 mg/kg), and high-dose (300 mg/kg)) groups (10 mice in per group). After 35 days, the physiological aging indices of mice were measured. JP and JF displayed significantly positive synergistic antiaging effects. Compared with an aging model control group, groups administered JP and JF showed increased indices for the thymus and spleen and significantly increased activities of SOD and GSH-PX in the heart, liver, spleen, and brain (R2 > 0.99, P < 0.01; R2 > 0.98, P < 0.01). The contents of MDA in heart, liver, spleen, brain and serum were significantly decreased (R2 > 0.95, P < 0.01), while those of HYP in skin and serum were significantly increased. The concentrations of neurotransmitters (NE, DA, 5-HT, 5-HIAA) in the brain and serum of mice were significantly increased (P < 0.01). These results indicated that JP and JF acted not only on relevant tissues or organs of mice, but on all body systems.

Abstract Objective This study aimed to identify the predictors and threshold of failure in neonatal acute respiratory distress syndrome. Methods Newborns with severe acute respiratory distress syndrome aged 0-28 days and gestational age ≥36 weeks were included in the study if their cases were managed with non-extra corporal membrane oxygenation treatments. Patients were divided into two groups according to whether they died before discharge. Predictors of non-extra corporal membrane oxygenation treatment failure were sought, and the threshold of predictors was calculated. Results A total of 103 patients were included in the study. A total of 77 (74.8%) survived hospitalization and were discharged, whereas 26 (25.2%) died. Receiver operating characteristic analysis of oxygen index, pH, base excess, and combinations of these indicators demonstrated the advantage of the combination of oxygen index and base excess over the others variables regarding their predictive ability. The area under the curve for the combination of oxygen index and base excess was 0.865. When the cut-off values of oxygen index and base excess were 30.0 and −7.4, respectively, the sensitivity and specificity for predicting death were 77.0% and 84.0%, respectively. The model with base excess added a net reclassification improvement of 0.090 to the model without base excess. Conclusion The combination of oxygen index and base excess can be used as a predictor of outcomes in neonates receiving non-extra corporal membrane oxygenation treatment for acute respiratory distress syndrome. In neonates with acute respiratory distress syndrome, if oxygen index >30 and base excess <−7.4, non-extra corporal membrane oxygenation therapy is likely to lead to death.

This study aimed to explore the effect of intravenous thrombolysis with alteplase on clinical efficacy, inflammatory factors, and neurological function in patients with acute cerebral infarction. A total of 120 patients with acute cerebral infarction were divided into two groups by the random number table method, with 60 patients in each group: observation group (intravenous thrombolysis with alteplase) and control group (intravenous thrombolysis with batroxobin). The clinical efficacy after a 14-day treatment was observed. Serum C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), CD62p, GMP-140, and neuron-specific enolase (NSE) were measured. Scores of National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) were determined. The total effective rate in the observation group was 81.67%, which was higher than the 61.67% in the control group (P<0.05). The improvement of inflammatory factors (CRP, TNF-α, IL-6, CD62p, GMP-140, and NSE), NIHSS, MMSE, and MoCA in the observation group was superior to that in the control group (all P<0.05). The modified Rankin scale at three months after hospital discharge in the observation group was lower than that in the control group (P<0.01). Intravenous thrombolysis with alteplase for acute cerebral infarction can enhance the clinical efficacy, alleviate inflammatory response and brain injury, and improve cognitive function, which is worthy of further clinical application and study.

Abstract Sclareol is an important intermediate for ambroxide synthesis industries. Hyphozyma roseonigra ATCC 20624 was the only reported strain capable of degrading sclareol to the main product of sclareol glycol, which is the precursor of ambroxide. To date, knowledge is lacking about the effects of sclareol on cells and the proteins involved in sclareol metabolism. Comparative proteomic analyses were conducted on the strain H. roseonigra ATCC 20624 by using sclareol or glucose as the sole carbon source. A total of 79 up-regulated protein spots with a >2.0-fold difference in abundance on 2-D gels under sclareol stress conditions were collected for further identification. Seventy spots were successfully identified and finally integrated into 30 proteins. The up-regulated proteins under sclareol stress are involved in carbon metabolism; and nitrogen metabolism; and replication, transcription, and translation processes. Eighteen up-regulated spots were identified as aldehyde dehydrogenases, which indicating that aldehyde dehydrogenases might play an important role in sclareol metabolism. Overall, this study may lay the fundamentals for further cell engineering to improve sclareol glycol production.

PURPOSE: To investigate the anticancer activity of ellagic acid (EA) in U251 human glioblastoma cells and its possible molecular mechanism. METHODS: The cells were treated with EA at various concentrations for different time periods. Cell viability and cell proliferation were detected by cell counting kit-8(CCK-8) assay and live/dead assay respectively. Cell apoptosis were measured with Annexin V-FITC/PI double staining method by flow cytometry and Mitochondrial membrane potential assay separately. Cell cycle was measured with PI staining method by flow cytometry. The expressions of Bcl-2, Survivin, XIAP, Caspase-3, Bax, JNK, p-JNK, ERK1/2, p-ERK1/2, p38, p-p38, DR4, DR5, CHOP and GRP78-related proteins were detected by western blot after EA treatment. RESULTS: Cell viability and proliferation of glioblastoma cells treated with EA were significantly lower than the control group. EA caused robust apoptosis of the glioblastoma cells compared to the control group. EA significantly decreased the proportion at G0/G1 phases of cell cycling accompanied by increased populations at S phase in U251 cell lines. And the expressions of anti-apoptotic proteins were dramatically down-regulated. CONCLUSION: Ellagic acid potentially up-regulated DR4, DR5 and MAP kinases (JNK, ERK1/2 and p38). EA also caused significant increase in the expressions of CHOP and GRP78. Our findings suggest that EA would be beneficial for the treatment of glioblastoma.