BACKGROUND: It has been verified pharmacologically that honokiol (HL) and magnolol (ML) have distinct effects on central inhibition and muscle relaxation, and some reports prove that they can relieve morphine withdrawal symptoms in animals.OBJECTIVE: To explore the effects of HL and ML on β-endorphin (β-EP) in relieving morphine withdrawal symptoms in rats.DESIGN: Randomized controlled study.SETTING: Pharmacological Department, the Medical School of Hubei national College.PARTICIPANTS: The experiment was conducted from 13 to 29 April,2003. Among 100 adult male SD rats, 30 rats as control group were randomly divided into three subgroups: saline group, HL group and ML group with 10 in each group. The other 70 rats as morphine-dependent group were divided into normal saline group, 5, 40 and 80 mg/kg HL and ML groups with 10 in each group.METHODS: 0.2 mL normal saline, 80 mg/kg HL and 80 mg/kg ML were injected intraperitoneally into rats in control group. The dose of morphine subcutaneously injected was increased in the rats in morphine-dependent group for 6 days to establish the model of acute morphine dependence and model of natural morphine withdrawal symptoms. The last injection was performed at 9:00 on the morning of day 6, and the intraperitoneal injection was performed at 10:30 on the same morning. 0.2 mL normal saline was injected into the rats of saline group. 5, 40 and 80 mg/kg HL and 5,40 and 80 mg/kg ML were given to rats in the other six groups, respectively. Starting from 11:00, half an hour later, all natural morphine withdrawal symptoms were observed in rats within an hour.compared among rats in the 7 morphine-dependent subgroups.control groups than in normal saline group (P ＜ 0.01), and HL group had higher β-EP level than ML group (P ＜ 0.05). β-EP level was obviously lower in morphine-dependent+saline groups than in control+saline groups (P ＜ 0.01).β-EP level in morphine-dependent+5, 40 and 80 mg/kg HL groups and in morphine-dependent+5, 40 and 80 mg/kg ML groups was obviously higher Scores of natural morphine withdrawal symptoms in rats of morphine-dependent group: Scores of wetshakes, penile licking, escape attempts, and weight lost in HL and ML subgroups were obviously lower than those in saline group (P ＜ 0.01).CONCLUSION: HL and ML can markedly restrain morphine withdrawal symptoms and this restraint is related to the increase of β-EP level in the brain. HL and ML have equal inhibitory effects on morphine-dependent rats, but HL is more effective than ML in normal rats.

OBJECTIVETo investigate the quantitative analysis based on three-dimensional computed tomography (3D-CT) in contouring surgery of complex craniofacial fibrous dysplasia (FD).

METHODS14 patients with craniofacial FD underwent 3D-CT scan. Axial images of patients with craniofacial FD were reconstructed into 3D model by using Mimics 10.0. Anatomical landmarks were located and the coordinate of the landmarks obtained. The differences between the right landmarks and the left were calculated and analyzed. Quantitative contouring surgery was performed based on the quantitative analysis result.

RESULTSWith the detail data from the 3D-CT analysis, the surgery of contouring was more safe and accurate with less operation time, less bleeding and good results.

CONCLUSIONSThe method of 3D CT quantitative analysis can provide precise information in the diagnosis and treatment planning of craniofacial deformity. Based on the result of 3D-CT quantitative analysis, the operations can be performed more accurately and safely with good symmetric consequence.

Aged ; Craniofacial Abnormalities ; diagnostic imaging ; Facial Bones ; abnormalities ; diagnostic imaging ; Fibrous Dysplasia, Polyostotic ; diagnostic imaging ; Humans ; Imaging, Three-Dimensional ; methods ; Tomography, X-Ray Computed ; methods

Objective To explore the related factors which affect the prognosis of traumatic brain injury (TBI) patients and provide the basis for clinical diagnosis and treatment.Methods One hundred and thirty-four TBI patients were selected from May 2017 to April 2018 in the Department of Neurosurgery of Wuwei Liangzhou Hospital.Death and discharge were used as endpoint events.The patients were divided into survival group (n =103) and death group (n =31) according to their prognosis.The abbreviated injury scale (AIS),glasgow coma scale (GCS),vital signs,thrombelastography,coagulation function and Chinese DIC scoring system (CDSS) of the patients at the time of admission was completed.The measurement data were compared with the t test,the count data were compared with chi-square test and logistic regression was used for multivariate regression analysis.Results The AIS was (4.7 ± 0.9) scores,CDSS was (7.8 ± 1.1) scores,GCS was (5.8 ± 1.4) scores,the R time of thrombelastography was (15.1 ± 5.6) min in death group.The AIS was (4.3 ± 0.8) scores,CDSS was (6.6 ± 0.6) scores,GCS was (8.6 ± 1.7) scores,the R time of thrombelastography was (8.6 ± 3.4) min in survival group.Single factor analysis showed that the AIS and CDSS were higher,GCS was lower and the R time of thrombelastography was longer in death group than in survival group,and there were statistical differences between the two groups (P ＜ 0.05).The multivariate logistic regression analysis showed that GCS,CDSS and R time were the independent risk factors of the prognosis of TBI patients.The area under the receiver operating characteristic curves of GCS,CDSS and R time were 0.731,0.648 and 0.635,respectively.Conclusion GCS,CDSS and R time can be used as predictive risk factors for prognosis of TBI patients.

BACKGROUNDColorectal carcinoma is one of the most common malignant tumors. Despite advances in therapy, mortality is still very high. The aim of this study was to evaluate the expression of paxillin in the human colon adenocarcinoma cell line SW480 and its role in cell cycle and apoptosis. We also investigated the expression of paxillin in colorectal carcinoma tissues and its relationship to clinicopathological features and survival.

METHODSPaxillin short hairpin RNA (shRNA) was constructed and transfected into the colon adenocarcinoma cell line SW480. The influence of paxillin shRNA on the cell cycle and cell apoptosis was analyzed by flow cytometry. Immunohistochemistry staining was used to assess the expression of paxillin and its association with the expression of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, p53 and Bcl-2 in 102 patients with primary colorectal carcinoma. Western blotting was also used to investigate the expression of paxillin. Medical records were reviewed and a clinicopathological analysis was performed.

RESULTSIn vitro, the percentage of cells in S phase was (45.23±1.05)%, (43.53±1.23)%, and (36.13±0.57)% in the blank control group, negative control group, and paxillin shRNA group respectively. It was significantly decreased in the paxillin shRNA group (P = 0.000). The early apoptosis index of the paxillin shRNA group (17.2±1.18%) was significantly increased compared to the control shRNA group ((13.17±1.15)%, P = 0.013). Paxillin was positive in 71 (69.6%) patients, and it was found to be overexpressed in tumor tissues compared with normal adjacent tissues. Paxillin positive rate was higher in patients who are less than 50-years old (100.0% vs. 65.6%, P = 0.016). Paxillin expression was associated with a high histologic grade of carcinoma (81.4% vs. 61.0%, P = 0.031), a high rate of regional lymph node metastasis (22.5% vs. 13.0%, P = 0.031), mesenteric artery lymph node metastasis (100.0% vs. 64.8%, P = 0.008), distant metastasis (94.1% vs. 64.7%, P = 0.016) and a high Tumor Node Metastasis (TNM) stage (94.1%, 73.2%, 60.0%, and 50%, P = 0.030). Multivariate analyses revealed that recurrence was associated with the rate of regional lymph node metastasis (P = 0.001) and paxillin expression (P = 0.024). Multivariate analysis indicated that the overall survival is related to the TNM stage (P = 0.000).

CONCLUSIONSIn vitro, paxillin may promote cell proliferation and inhibit apoptosis in SW480 cells. Paxillin may be a potential metastasis predictor, and an independent prognosis factor of recurrence. It may also be related to poor patient outcomes, but was not an independent predictor of survival.

Apoptosis ; genetics ; physiology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Male ; Paxillin ; genetics ; metabolism ; RNA, Small Interfering ; genetics

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.