Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

Objective: Symptomatic intracranial hemorrhage (sICH) is one of the severe complications of ischemic stroke thrombolysis. Several prognostic scales have been developed to predict the risk of sICH. The performance of seven scales was compared in a single center cohort. Methods: Data of patients with consecutive ischemic stroke who received 0.9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis within 4.5 h time window from stroke onset were collected. Seven scales that can provide an estimate of risk of sICH were identified and evaluated: Hemorrhage After Thrombolysis (HAT), blood Sugar, Early infarct signs, (hyper) Dense cerebral artery sign, Age, National Institutes of Health (NIH) Stroke Scale (SEDAN), Stroke Prognostication using Age and NIH Stroke Scale (SPAN)-100, Safe Implementation of Thrombolysis in Stroke (SITS), Total Health Risks In Vascular Events (THRIVE), Glucose at presentation, Race (Asia), Age, Sex (male), systolic blood Pressure at presentation, and Severity of stroke at presentation (NIH Stroke Scale; GRASPS) and Multicenter Stroke Survey (MSS). The area under the receiver operating characteristic curve (AUROC) was calculated and Logistic regression and the Hosmer-Lemeshow test were also performed. Results: The current study included 293 patients, of whom 7.85% (23/293) had sICH by National Institute of Neurological Disorders and Stroke (SICH_NINDS), 5.46% (16/293) by Europe Cooperative Acute Stroke Study Ⅱ (SICH_ECASSⅡ) and 4.44% (13/293) by Safe Implementation of Thrombolysis in Stroke (SICH_SITS) criteria. SEDAN had the highest AUROC for predicting sICH: sICH_NINDS: AUROC=0.843, OR=3.167, 95%CI 2.106-4.762, P<0.01; sICH_ECASSⅡ: AUROC=0.797, OR=2.509, 95%CI 1.652-3.812, P<0.01; sICH_SITS: AUROC=0.784, OR=2.172, 95%CI 1.405-3.357, P<0.01. And SPAN-100 had the lowest AUROC among all the seven scales and was only associated with risk of SICH_NINDS in regression analysis. Furthermore, when sub-grouped the cohort into anterior circulation infarction and posterior circulation infarction, regression analysis suggested that all the seven scales were however not associated with sICH risk in patients with posterior circulation infarction. Conclusions SEDAN constantly had the highest predictive power, SPAN-100 had the worst. The seven scales studied could not predict sICH in posterior circulation infarction.

Objective To explore the role of CORM-3 in alleviating cognitive dysfunction and cortical neuronal pyroptosis of rats exposed to hemorrhage shock and resuscitation. Methods One hundred and sixty-eight male SD rats, weighting 350-400 g, in accordance with random number table, were divided into 4 groups (n=42):sham-operated group, hemorrhage shock and resuscitation (H group), hemorrhage shock and resuscitation plus CORM-3 (CO group), hemorrhage shock and resuscitation plus iCORM-3 (ICO group). The rat hemorrhagic shock resuscitation models were established in H, CO and ICO groups:bleeding from femoral vein was performed to achieve mean arterial pressure of 25-35 mmHg (1 mmHg=0.133 kPa) for 60 min;and then, the collected blood was returned to the body within 15 min to reach the initial blood pressure level as resuscitation, and normal saline was injected if necessary. The rats in CO group were injected CORM-3 (4 mg/kg) via femoral vein after resuscitation, the rats in ICO group were injected iCORM-3 (4 mg/kg), and rats in the sham-operate group and H group were only injected equal amount of normal saline containing DMSO. Rats were sacrificed for cortex 12 h after end of resuscitation;CO content was assessed by gas chromatograph assay; Western blotting was used to detect the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and BTB-CNC homology 1 (Bach1) in the nuclear, and heme oxygenase-1 (HO-1), interleukin (IL)-1β and IL-18 in cytosol; and neuronal pyroptosis rate was detected by cleaved caspase-1-Cy3/neuron-specific nucleoprotein (NeuN)-FITC/DAPI. Thirty d after resuscitation, open field test was used to assess the cognitive ability of the rats. Results At 12 h after resuscitation, as compared with sham-operated group, rats in the H, CO and ICO groups had significantly increased CO content, neuronal pyroptosis, ratio of Nrf2/Bach1, and expressions of HO-1, IL-1β and IL-18, statistically longer time spending in the central square, significantly smaller times crossing the grid and times standing on the back legs (P<0.05). As compared with H and ICO group, CO group had significantly increased CO content, ratio of Nrf2/Bach1, and HO-1 expression, times crossing the grid, times standing on the back legs, but significantly decreased neuronal pyroptosis, expressions of IL-1β and IL-18, and time spending in the central square (P<0.05). Conclusion CORM-3 can reduce the neuronal pyroptosis rate and alleviate cognitive dysfunction in rats with hemorrhagic shock and resuscitation, whose mechanism may be related to the increase of HO-1 expression after up-regulation of Nrf2/Bach1 ratio.

Objective To establish a risk rating scale for central lymph node metastasis in papillary thyroid carcinoma and make risk stratification.Methods Data of 502 patients with PTC who were treated in Beijing Shijitan Hospital between January 2010 and June 2015 were retrospectively analyzed.The independent predictors for CLNM were found.Then a risk rating scale was established and stratification risk was made.The diagnostic value of the risk rating scale in predicting CLNM was evaluated.Data of 100 patients with PTC who were treated in Beijing Shijitan Hospital between July 2016 and June 2016 were used to validate the risk rating scale.Results A cutoff value of 5 points was found to be the best prediction for CLNM,with the sensitivity and specificity were 73.8％ and 70.2 ％.We definite score ≤ 4.5 as low risk for CLNM,as well as score from 5 to 7 as middle risk,score ≥ 7.5 as high risk.The other data of 100 patients was used to validate the risk rating scale.The sensitivity and specificity were 79.5％ and 78.7 ％ respectively.The positive predictive value and the negative predictive value were 70.5％ and 85.7％ respectively.Conclusions The risk rating scale provide a convenient,intuitive and quantized method to predict CLNM,which is helpful to select suitable surgical strategy and reduce operative complications.

Objective To investigate the expression level and clinical significance of long non-coding RNA(LncRNA) growth arrest specific gene-antisense 1(GAS8-AS1) in papillary thyroid microcarcinoma(PTMC) patients. Methods We investigated the expression profile of GAS8-AS1 in tissue samples of patients with PTMC as well as nodular goiter(NG) by quantitative real-time polymerase chain reaction(RT-qPCR). Results GAS8-AS1 in cancer tissue was down-regulated in PTMC patients compared with adjacent thyroid tissue and NG samples(P<0.05). Lower level of GAS8-AS1 was also correlated with central cervical lymph node metastasis(CLNM, P<0.05). The area under the ROC curve for GAS8-AS1 was up to 0.717 3 in CLNM prediction(P<0.05). Conclusion GAS8-AS1 may act as a potential biomarker for PTC diagnosis and CLNM prediction.

Objective:To treat the mixed and deeper infantile hemangioma with ladder dosage propranolol, and to explore its efficacy and safety.Methods:A total of 98 infants with hemangioma were treated by ladder treatment of propranolol.Before treatment,comprehensive assessments of electrocardiogram(ECG),heart color ultrasound, blood glucose,liver function,kidney function,myocardial enzymes and blood routine were conducted.After excluding contraindications,the dose of propranolol incrementally doubled from 0.5 mg·kg-1·d-1 to 4.0 mg·kg-1·d-1.Propranolol was taken 3 times a day.Before and after medication for 1 and 2 h,ECG was monitored.The changes of tumor size,texture,color and other changes or an onset of adverse reactions were dynamicly observed.The infants were visited every month.The efficacy was evaluated using Achauer system.Results: After medication,98 cases had different degrees of color changes or tumor consistency softening.After the dosage of propranolol was increased to 4.0 mg·kg-1·d-1,the change of tumor was the fastest.According to the 4-grade method, there were 84 cases(85.71%) as gradeⅣ (excellent),2 cases (2.04%) as grade Ⅲ (good),4 cases (4.08%) as gradeⅡ (medium)and 8 cases (8.16%) as gradeⅠ (poor).The curative effect of mixed hemangioma was better than that of deeper hemangioma(P<0.05).The recovery time of 74 cases of hemangiomas was 6 months.The major adverse reactions were heart rate decline(5/98,5.10%),drowsiness(3/98,3.06%),diarrhea(7/98,7.14%),loss of appetite (1/98,1.02%), and convulsions (2/98,2.04%).After treatment,all adverse reactions disappeared.Two months after drug withdrawal there were 4 cases of recurrence,and they were continously treated with propranolol.Conclusion: The efficacy of oral ladder dosage propranolol in treatment of mixed and deeper infantile hemangioma is increased significantly and there are no significant adverse reactions.

To develop a simple and easy promotion risk score to identify individuals with undiagnosed papillary thyroid carcinoma (PTC), and further to compare the diagnostic efficiency of PTC risk sore with fine needle aspiration cytodiagnosis (FNAC). in order to optimize the screening process of PTC. A sample of 1003 individuals aged 11-82 years underwent a surgical treatment of thyroid nodule participated in the study. The risk score was developed by stepwise backward multiple logistic regression. And using the receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy, the best diagnostic cut-off point and the risk stratification of malignant. Compare the sensitivity, specificity, accuracy, and area under curve ( AUC) of PTC risk score, FNAC and their combined diagnosis to judge their diagnostic efficiency. The risk score included age, TSH, nodule morphology and boundary by palpation, nodule characteristics, shape, boundary, calcification and blood flow signal by ultrasound. Its AUC= 0. 815, 6 point was the best cutoff point to differentiate benign from malignant thyroid nodules, and risk stratification of thyroid carcinoma were divided into four levels: very high risk group (score ≥ 9 points), high risk group ( score were 5-8 points), moderate risk group ( score were 3 ~ 4 points), low risk group ( score ≤ 2 points). The sensitivity, specificity, and accuracy of FNAC were 86. 3% , 90. 0% , and 87. 0% respectively, AUC=0. 891, while the sensitivity, specificity, and accuracy of PTC risk rating scale were 83. 8% , 70. 0% , and 81. 0%respectively, AUC = 0. 822. The sensitivity, specificity, and accuracy of their combined diagnosis were 97. 5% , 85. 0% , and 95. 0% , AUC=0. 965. This risk score can be used as a screening method before FNAC. If combined with FNAC, it may improve the diagnostic efficacy of PTC, and thereby possibly minimizing the unnecessary invasive examination and surgical treatment for patients with thyroid nodules and reducing personal costs.

Objective To construct plasmid vectors of calmodulin(CaM)Mg2+binding site mutants,and to express,purify and identify the mutant proteins. Methods Three kinds of cDNAs coding for the mutated CaM were cloned into pGEX?6P?3 plasmid vectors. These recombinant plasmids were transfected into Escherichia coli BL21 to express GST fusion proteins of CaM mutants. The fusion proteins were purified with Glutathione?Sep?harose 4B beads and PreScission protease. Results Both enzyme digestion analysis and DNA sequence identification proved the successful con?struction of the CaM mutant plasmids. SDS?PAGE results showed the high purity of each CaM mutant protein. The concentrations of three CaM mu?tants were around 1.0 mg/mL. Conclusion Prokayotic expression vectors of CaM Mg2+binding site mutants were successfully developed,and the eli?gible CaM mutant proteins were obtained. This study provided an important basis for further study on CaM’s biological function.

BACKGROUND:Most of lumbar degenerative diseases, such as lumbar instability, lumbar disc herniation and discogenic lumbago, need lumbar spinal fusion for the spine stability, but the choice of internal fixation approaches is controversial.
OBJECTIVE:To compare the effectiveness between lateral lumbar interbody fusion with single cage and single cage combined with unilateral pedicle screw fixation for the 4th and 5th single-level lumbar degenerative disease.
METHODS:The clinical data of patients with single-level lumbar degenerative diseases (L4 and L5) undergoing lateral lumbar interbody fusion with single cage in 30 cases (experimental group) and single cage combined with unilateral pedicle screw fixation in 45 cases (control group) were analyzed retrospectively, and the curative effects were compared between the two groups.
RESULTS AND CONCLUSION:Al patients in the two groups were fol owed up for 13 months on average (ranged from 10 to 37 months). The incisions in the two groups were stage I healing. One case in the experimental group occurred cage displacement, but no obvious syndromes were detected. No significant difference in the effective rate after operation, hospital stay, and volume of drainage was detected (P>0.05). The operative time and bleeding volume in experimental group were better than those in the control group (P<0.05). ODI and JOA scores were significantly improved after treatment when compared with preoperative ones in the two groups (P<0.05), but no significant difference was visible between the two groups (P>0.05). The effectiveness of lateral lumbar interbody fusion with single cage and single cage combined with unilateral pedicle screw fixation for single-level degenerative lumbar diseases was similar. However, the former has the advantages of less invasion and quick recovery.

Objective To investigate the effect of ellagic acid extracted from gallnut on multiple myeloma SP2 / 0 cell line and related mechanisms. Methods Multiple myeloma SP2 / 0 cell line was treated for 48 h with different concentrations of ellagic acid in vitro. Cell morphology,proliferation,apoptosis and cell cycle were analyzed with microscope,MTT experiment and flow cytometry,respectively. Tumor cell proliferation and apoptosis-related gene expression of COX-2 were detected by Western blotting. Results Cell cycle was arrested at the G1 phase 48 h after treatment with ellagic acid, the cell in G1 were (55. 21±3. 01)% , (64. 48 ± 0. 43)% , (75. 10 ± 2. 46)% , respectively, with significant difference as compared with control group [(34. 04±1. 74)% ,P<0. 01]. Cell suppression rate (21. 18±5. 92)% ,(44. 58±3. 43)% and (70. 15±2. 90)% ,respectively, in 20,40 and 60 μg·mL-1 ellagic acid treatment groups. Compared with the control group,the differences were significant (P<0. 01). Cell apoptosis rate was (9. 60 ± 0. 56)% , (19. 30 ± 1. 51)% and (35. 10 ± 5. 26)% , respectively, in 20,40 and 60 μg·mL-1 ellagic acid treatment groups,with significant differences as compared with the control group[(3. 23±0. 85)% ,P<0. 01]. With the increase of drug concentration,COX-2 expression was decreased. Conclusion Ellagic acid can inhibit myeloma SP2 / 0 cell proliferation and promote apoptosis.