ABSTRACT
Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
ABSTRACT
Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Subject(s)
Animals , Male , Mice , Brain , Cocaine , Conditioning, Operant , Extinction, Psychological , Lipidomics , Simvastatin/therapeutic useABSTRACT
@#Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.
ABSTRACT
Objective To explore the clinical features and surgical treatment of cervical tuberculous lymphadenopathy associated with abscess formation.Methods The clinical data of 95 cases of cervical tuberculous lymphadenopathy associated with abscess formation were reviewed and analyzed retrospectively.All the patients were treated in Shenzhen Third People's Hospital during the period from February 2012 to May 2014.Results The mean age of the 95 patients was (27.8±8.2) years.The average duration of the disease was 4.0 months.The tuberculous lymphadenopathy was most frequently found in Level Ⅳ cervical lymph nodes.Thirty-four patients were complicated with pulmonary tuberculosis.History of surgical treatment for tuberculous cervical lymphadenopathy was reported in 26 cases.Sixty-five patients were managed with incision and drainage plus dress changing.Twenty-two patients underwent abscess rinsing,excision and primary wound closure.And 8 patients received excision of ulcers and sinuses,and lymphadenopathy cleaning.The average healing time was (2.11± 1.76) months for incision and drainage.Abscess and ulcer reoccurred in 18 of the 65 patients after healing completely by incision and drainage.All the patients treated by the other two surgical modalities were cured as primary healing except 2 patients,who received local flap grafting after primary surgery.Conclusions Cervical tuberculous lymphadenopathy associated with abscess formation has special features in diagnosis and treatment.Surgical approach is usually effective if optimized for individual patients.
ABSTRACT
Objective@#Leukocyte mediated IL-6 (IL-6) plays an important role in chronic viral hepatitis pathogenesis and related liver diseases, We did a large sample-size case-control study and clinical data analysis to find association between IL-6 single nucleotide polymorphism and HBV susceptibility, and to achieve the detection of the body on the expression of IL-6 for the prevention and treatment of HBV infection.@*Methods@#Totally 848 HBV patients and 894 healthy controls in Shenzhen were selected and rs1800796 genotypes were determined by TaqMan assays.@*Results@#The result showed that rs1800796 polymorphism was associated with susceptibility to HBV infection (P=0.0003, odds ratio (OR)=1.43, the difference was statistically significant.@*Conclusions@#The single nucleotide polymorphism of IL-6rs1800796 locus was associated with the susceptibility of HBV infection in Chinese population, and the rs1800796 G allele is a protective gene for HBV infection.
ABSTRACT
Objective To introduce a new method performing umbilicus abdominal access during laparoscopy. Methods In a prospec-tive,362 patients received laparoscopic appendectomy in October 2012 to October 2014 were oberserved in this study. The clinical data,the time of the progress of making umbilicus abdominal access,complications and the state of the wound were recorded. Results The performing time of the trocar in umbilicus was (42. 3 ± 27. 1)s. Conclusion The method Cut-open,is simple,fast and save,which is worth to promoting in laparoscopic surgery.
ABSTRACT
AIM:To investigate the role of minocycline on glutamate uptake in the periventricular zone and its putative mechanism after hypoxic exposure in neonatal rats.METHODS: A model of hypoxic-ischemic brain damage (HIBD) was developed by putting postnatal 1 d rat pups in 5%O2 for 3.5 h.The glutamate level in periventricular zone was measured by liquid chromatography coupled with tandem mass spectrometry assay ( LC-MS/MS) after hypoxic exposure for 4 h and 1 d.The dynamic changes of glutamate transporters EAAT1, and EAAT2 during developmental period in periventricular zone were determined by Western blot.Moreover, the expression of EAAT1, EAAT2, Iba-1, IL-1β, TNF-αand TGF-β1 was also detected by Western blot after hypoxic exposure for 4 h and 1 d in that region.The effects of mino-cycline on all parameters mentioned above were tested after minocycline treatment at the same time points and in the same region.RESULTS:After hypoxic exposure, glutamate level was increased, but it was decreased after minocycline treat-ment.EAAT1 and EAAT2 kept a low expression level at the first postnatal week, but a predominant elevation was found at the end of the second postnatal week.The expression of EAAT1, EAAT2, Iba-1, IL-1βand TGF-β1 was increased at 1 d after hypoxic exposure.EAAT1 and TNF-αexpression was significantly up-regulated, while EAAT2 was down-regulated af-ter minocycline treatment.CONCLUSION: Minocycline inhibits the increase in the glutamate level after hypoxia in periventricular region of the neonatal rats.The mechanism may relate to the selective regulation of glutamate transporters, rather than the inhibition of neuroinflammation in periventricular zone.
ABSTRACT
Objective To investigate the mechanism related to reduced antibiotic sensitivity of Acinetobacter baumannii inducted by meropenem in vitro.Methods Three strains of clinically isolated carbapenems-sensitive Acinetobacter baumannii were induced by meropenem in vitro, and the mutant strains (MS1, MS2 and MS3) were obtained.Minimal inhibitory concentrations (MICs) of antimicrobial agents to strains before and after induction were determined by automatic drug sensitivity analyzer .The homology of strains was analyzed by Enterobacterial repetitive intergenic consensus -polymerase chain reaction ( ERIC-PCR).Modified Hodge test and EDTA-Na2-double disk synergy test were used to detect carbapenemase and metallo-β-lactamase (MBL), respectively.Main carbapenemase genes were detected by PCR and followed by DNA sequencing.Expressions of adeB and outer membrane proteins in strains before and after induction were detected with fluorescence quantitative PCR and SDS -polyacrylamide gel electrophoresis , respectively.t test was used for data analysis .Results The sensitivity of mutant Acinetobacter baumannii strains to meropenem and most antibiotics was reduced , except to imipenem, amikacin and polymyxin; and the reduced sensitivity to meropenem in MS2 and MS3 was of genetic stability.ERIC-PCR showed 100%homology between the mutant strains and parental strains .Both carbapenemase and metallo -β-lactamase were negative in mutant strains and parental strains , and only OXA-51 gene was found.The expressions of adeB gene in mutant strains were 24.26 ±0.91, while those in parental strains were 22.81 ±0.38, and the difference was not significant (t =2.534, P >0.05).Outer membrane protein with molecular weight 54 000 was missing in MS1, while that with molecular weight 47 000 was missing in MS2 and MS3.Conclusion Reduced antibiotics sensitivity in meropenem -induced Acinetobacter baumannii may be correlated with the deficiency of outer membrane protein with molecular weight 47 000.
ABSTRACT
Objective To evaluate the interference of occult blood in urine (urinary hemoglobin) and to determine the protein in urine by benzethonium chloride .Methods By reference to EP7‐A2 of CLSI ,urine containing different concentrations of hemoglobin were preparated to produce the dose‐effect curve,while 50 cases of clinical urine with varying degrees of occult blood were col‐lected for clinical sample bias test.Urinary protein was quantified by benzyl chloride in DPP roche comparing with sulfosalicylic acid method .Results When the urinary hemoglobin was 0 .2 g/L or higher ,the determined result of urinary protein of urinary pro‐tein would be significantly interfered by benzethonium chloride method .The clinical sample bias testshowed that clinical urine with different degrees of occult blood caused positive interference to the determination of protein by benzethonium chloride .Conclu‐sion Urine samples with occult blood and /or containing red blood cells should be emphasized and evaluate the accuracy when the urinary protein is quantified by benzyl chloride .If necessary ,it should be confirmed by sulfosalicylic acid .
ABSTRACT
Objective To explore the effectiveness of Liberman mental rehabilitation training on social function of the patients with chronic schizophrenia. Methods Sixty-two in-patients with stable chronic schizophrenia were trained for 12 weeks with Liberman mental rehabilitation technique. The social disability screening schedule (SDSS) was used to assess the social function before and after training. Result After training, the scores by SDSS were lower those than before training with statistical significance (P < 0.001). Conclusion Liberman mental rehabilitation training can improve the social function of patients with chronic schizophrenia.
ABSTRACT
Objective To study the expression of clusterin (CLU) and P-glycoprotein (P-gp) in hepatic cell carcinoma (HCC) and its relationship.Methods The expression of CLU gene in the tissue of H CC (41 cases),cirrhosis(10 cases) and normal liver (10 cases) and the expression of P-gp in the tissue of HCC were detected by immunohistochemical method.Results The positive expression rate of CLU was 82.93％(34/41) in HCC,and negative or weak positive were detected in cirrhosis and normal liver tissue.The positive expression rate of CLU was significantly correlated with Edmondson's histological grade (P ＜ 0.05),but had no correlation with patients' age,sex and cirrhosis (P ＞ 0.05).The positive expression rate of P-gp in HCC was 70.73％(29/41).There was significant correlation between the expression of CLU and P-gp (P ＜ 0.05).Conclusions The over expression of CLU is significantly associated with clinical multidrug resistance in HCC.It should be a potential target for treatment of HCC.
ABSTRACT
Objective To evaluate the safety and efficacy of single and local use of a China-made compound betamethasone injection in the treatment of lichen simplex chronicus. Methods A multi-center,randomized, parallel controlled study was conducted. Patients with lichen simplex chronicus were divided into test and control groups to receive a single dose of intralesional compound betamethasone injection made in China or Schering-Plough Labo N.V. Belgium. Patients were visited for the evaluation of efficacy and safety of the China-made injection at the beginning of the treatment (DO), on week 2 (D14) and 4 (D28) after the initiation of treatment. Results A total of 144 patients were enrolled, among which, 68 in the control group and 71 in the test group completed the trial. FAS analysis on week 4 revealed that the response rate and healing rate were 86.11% and 59.72% in the control group, respectively, 86.11% and 54.17% in the test group, respectively (χ2=0.00,0.45,respectively,both P>0.05).There was no severe adverse event in either group after the treatment, and only mild atrophoderma occurred in one patient in the control group, which was improved spontaneously within several weeks of follow-up. There was no statistically significant difference in the occurrence of side reactions between the two groups (P> 0.05). Conclusion The China-made compound betamethasone injection is effective and safe for the treatment of lichen simplex chronicus.
ABSTRACT
Lipases are widely used enzymes in biotechnology. Although they catalyze the same reaction, their sequences vary. Therefore, it is highly desired to develop a fast and reliable method to identify the types of lipases according to their sequences, or even just to confirm whether they are lipases or not. By proposing two scales based pseudo amino acid composition approaches to extract the features of the sequences, a powerful predictor based on k-nearest neighbor was introduced to address the problems. The overall success rates thus obtained by the 10-fold cross-validation test were shown as below: for predicting lipases and nonlipase, the success rates were 92.8%, 91.4% and 91.3%, respectively. For lipase types, the success rates were 92.3%, 90.3% and 89.7%, respectively. Among them, the Z scales based pseudo amino acid composition was the best, T scales was the second. They outperformed significantly than 6 other frequently used sequence feature extraction methods. The high success rates yielded for such a stringent dataset indicate predicting the types of lipases is feasible and the different scales pseudo amino acid composition might be a useful tool for extracting the features of protein sequences, or at lease can play a complementary role to many of the other existing approaches.
Subject(s)
Amino Acids , Chemistry , Computational Biology , Lipase , Chemistry , Classification , Models, Chemical , Sequence Analysis, Protein , MethodsABSTRACT
Types of cofactor independency for newly found oxidoreductases sequences are usually determined by experimental analysis. These experimental methods are both time-consuming and costly. With the explosion of oxidoreductases sequences entering into the databanks, it is highly desirable to explore the feasibility of selectively classifying newly found oxidoreductases into their respective cofactor independency classes by means of an automated method. In this study, we proposed a modified Chou's pseudo-amino acid composition method to extract features from sequences and the k-nearest neighbor was used as the classifier, and the results were very encouraging. When lambda = 48, w = 0.1, the areas under the ROC curve of k-nearest neighbor in 10-fold cross-validation was 0.9536; and the success rate was 92.0%, which was 3.5% higher than that of pseudo-amino acid composition. It was also better than all the other 7 feature extraction methods. Our results showed that predicting the cofactors of oxidoreductases was feasible and the modified pseudo-amino acid composition method may be a useful method for extracting features from protein sequences.
Subject(s)
Amino Acid Motifs , Amino Acids , Coenzymes , Chemistry , Computational Biology , Models, Chemical , Oxidoreductases , Chemistry , Predictive Value of TestsABSTRACT
Objective:To study the feasibility of surgical techniques and clinical experience of the airbag-free separation of nail and the whole extraperitoneal laparoscopic hernia repair(TEP).Methods:Ninty-three cases of inguinal hernia.Patients were treatecl in our hospital from March 2005 to January 2009,with 39 cases of regular.Free air and non-stapling of mesh TEP and 54 cases of routine open tension-free hernioplasty.Results:The operation times were as follows:TEP Group,unilateral hernia(101.3?15.6 min),bilateral hernia(138.4?17.3 min);Open Group,unilateral hernia(81.6?7.6 min),bilateral hernia 175.8?22.0 min.The couplications in TEP Goup inclucled 3 cases of retroperitoheal rupture,3 cases of intra-operative vascular injury,and 2 cases of postoperative scrotal hematoma.Nine cases of sacrotal hematoma,4 cases of infective and 6 cases of long-term pain in the groin area happened in open Group.Conclusion:TEP of free balloon separator with no stapling patch is safe,reliable,less post-operative complications and especially suitable for bilateral hernia.