Objective To investigate the effects of ketamine on neuronal nitric oxide synthase (nNOS) activity and carboxy-terminal PDZ ligand of nNOS (CAPON) expression in the prefrontal lobe of mentally depressed rats.Methods Adult male Sprague-Dawley rats,aged 2.5-3.0 months,weighing 210-260 g,were used in the study.Menial depression was induced by exposing the rats to chronic unpredictable mild stress.Twenty-four animals in which mental depression was successfully induced were randomly divided into 2 groups (n =12 each):mental depression group (group D) and ketamine group (group K).Another 12 rats were chosen and served as control group (group C).Group K received intraperitoneal ketamine 10 mg/kg once a day for 7 consecutive days,while groups C and D received intraperitoneal normal saline 10 ml/kg instead of ketamine.Sucrose preference test and open field test were performed before administration and at 1 day after the end of administration.The total distance,number of rearing and sucrose preference percentage (SPP) were recorded.The rats were sacrificed 1 day after the last test for determination of the expression of nNOS and CAPON protein (using immuno-histochemistry)and mRNA (by RT-PCR) in the prefrontal lobe.Results Compared with group C,the total distance was shortened,the number of rearing and SPP were significantly decreased,the expression of nNOS protein and mRNA was up-regulated and the expression of CAPON protein and mRNA was down-regulated in groups D and K (P ＜ 0.05).Compared with group D,the total distance was prolonged,the number of rearing and SPP were significantly increased,the expression of nNOS and mRNA was down-regulated and the expression of CAPON protein and mRNA was up-regulated in group K (P ＜ 0.05).Conclusion Ketamine can improve the depressive state through promoting the expression of CAPON and inhibiting nNOS activity in the prefrontal lobe of mentally depressed rats.

Breast Neoplasms ; genetics ; pathology ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 9 ; Female ; Genome, Human ; Humans ; Nucleic Acid Hybridization ; methods ; Phyllodes Tumor ; genetics ; pathology

UNLABELLEDTo study the method for dose calculation and beam weight optimization of intensity-modulated radiation therapy (IMRT).

METHODSThe IMRT dose calculation model based on two-dimensional convolution was constructed, the program of dose calculation and beam weight optimization with genetic algorithm was written with Visual c#.Net, and the optimization results were analyzed.

RESULTSGenetic algorithm optimization of beam weights can produce highly conformal dose distributions within a clinically acceptable computation time.

CONCLUSIONGenetic algorithm is valid and efficient in IMRT beam weight optimization, which may facilitate IMRT treatment planning.

Algorithms ; Humans ; Models, Statistical ; Models, Theoretical ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; methods ; Radiotherapy, Conformal ; methods ; standards

BACKGROUNDThe non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD.

METHODSIn this randomized perspective clinical trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two groups of patients in a cross-over design. Blood pressure (BP), creatinine clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant.

RESULTSUrinary excretion of cytokines (granulocyte colony stimulating factor (GCSF), intercellular cell adhesion molecule-1 (ICAM-1), interferon γ (IFN-γ), interleukin 1β (IL-1b), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1d (MIP-1d)) in group B (irbesartan 300 mg/d) was significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-γ, IL-1a, IL-11, IL-12p40, MCP-2, MIP-1a), while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1a by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.

CONCLUSIONIrbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cytokines excretion in the urine of CKD patients.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Biphenyl Compounds ; adverse effects ; therapeutic use ; Chronic Disease ; Creatinine ; metabolism ; Cross-Over Studies ; Cytokines ; urine ; Humans ; Kidney Diseases ; drug therapy ; immunology ; Prospective Studies ; Tetrazoles ; adverse effects ; therapeutic use

OBJECTIVETo investigate the possible role of STAT3 and p38 in the carcinogenesis of sporadic colorectal tubular adenoma.

METHODSThe expression of STAT3 and p38 at protein level was studied in 107 sporadic colorectal tubular adenomas with different dysplasia (SCTA-D) or with cancerous changes (SCTA-Ca) by immunohistochemical staining method, meanwhile the expression of STAT3 at mRNA level was detected by in situ hybridization.

RESULTSImmunohistochemical staining results showed that the positive expression rate of STAT3 and p38 was 12.0%, 59.0%, 91.7% and 8.0%, 47.0%, 91.7% in normal colorectal mucosa (NCM), SCTA-D and SCTA-Ca, respectively, with a statistically significant difference of STAT3 and p38 expression among the SCTA-D, SCTA-Ca and NCM (P < 0.05). The expression of STAT3 and p38 was positively correlated with the degree of dysplasia from mild to severe SCTA-D (P < 0.05). In situ hybridization results showed that the positive expression rate of STAT3 at mRNA level in NCM, SCTA-D and SCTA-Ca was 8.00%, 51.8% and 100.0%, respectively, with a statistically significant difference among these either (P < 0.05). The positive expression of STAT3 at mRNA level was not only positively correlated with the degree of dysplasia (P < 0.05), but also with the expression of p38 (P < 0.05).

CONCLUSIONSTAT3 and p38 may be involved in the carcinogenesis of sporadic colorectal tubular adenoma.

Adenocarcinoma ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Cell Transformation, Neoplastic ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Intestinal Mucosa ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; RNA, Messenger ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

Objective To investigate the molecular mechanism of ALKBH5 reducing sepsis-induced myocardial dysfunction(SIMD).Methods The expression levels of ALKBH5 and TRAF1 in the blood of 50 SIMD patients and 50 healthy individuals were detected using reverse transcription fluorescence quantitative polymerase chain reaction(RT-qPCR),and the correlation between their expression levels was analyzed by person analysis;In vitro experiments,H9C2 myocardial cells were divided into 7 groups according to over expression of TARF1 and knockdown ALKBH5.The molecular mechanism of ALKBH5 targeting TRAF1 to regulate lipopolysaccharide(LPS)induced myocardial cell damage was studied through experiments such as CCK8,ELISA,and Western blot;In the in vivo experiment of rats,LPS induced rats were divided into 6 groups according to over expression of TARF1 and knockdown ALKBH5.Experimental methods such as colorimetry,ELISA,Western blot,HE staining,and immuno-histochemistry were used to study the mechanism of ALKBH5 targeting TRAF1 through NF-κB pathway in reduc-ing myocardial cell damage.Results The expression levels of ALKBH5 and TRAF 1 were downregulated in SIMD,and the Pearson analysis showed a positive correlation between them(P<0.001);In vitro experiments showed that overexpression of TRAF1 promotes cell proliferation,inhibits the expression of inflammatory factors and proteins involved in the NF-κB pathway,and knockdown ALKBH5 obtain the opposite resulst;In vivo experi-ments in rats showed that knockdown ALKBH5 promotes injury in cardiomyocytes,expression of inflammatory factors and NF-κB-related pathway proteins,and nuclear translocation of NF-κB p65 protein,but the overexpression of TRAF 1 yielded the opposite results.Conclusion ALKBH5 increases the stability of TRAF1 by reducing its meth-ylation,thereby inhibiting NF-κB pathway,thereby reducing SIMD.

Adolescent ; Adult ; Aged ; Alcohol Drinking ; adverse effects ; China ; epidemiology ; Educational Status ; Female ; Humans ; Hypertension ; epidemiology ; etiology ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Smoking ; adverse effects

OBJECTIVEThe Ala499Val (C > T) and Lys939Gln (A > C) of the XPC gene are two potentially functional nonsynonymous polymorphisms, which affect the rate of DNA repair and might change XPC production and activity. This study aimed to explore the distribution of these two polymorphisms in the Chinese Han population and their relationship with male infertility.

METHODSWe genotyped the two polymorphisms of the XPC gene by the PCR-restriction fragment length polymorphism (PCR-RFLP) method in 318 infertile patients and 228 fertile male controls, detected the frequency of the alleles, and analyzed both the individual and the joint contribution of the two polymorphisms to male infertility.

RESULTSFor the Ala499Val (C > T) polymorphism, the frequencies of the CC, CT, and TT genotypes were significantly different in distribution between the patients and the controls (P = 0.020). Males with the TT genotype had a lower risk of male infertility than those with the CC genotype (adjusted OR = 0.49, 95% CI: 0.23-0.88), and even lower than those with both CC and CT genotypes (adjusted OR = 0.39, 95% CI: 0.22-0.71). The Lys939Gln (A > C) polymorphism was not related with male infertility. The combined genotype analysis showed that the individuals with 1-4 risk alleles had a significantly higher risk of male infertility (adjusted OR = 2.75, 95% CI = 1.50-5.04) than those with 0 risk allele.

CONCLUSIONThe Ala499Val (C > T) polymorphism of the XPC gene is correlated with male infertility and may be a potential genetic risk factor for male infertility in the Chinese Han population.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; DNA Repair ; DNA-Binding Proteins ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Genetic ; Risk Factors

Objective To evaluate the technique and efficacy of retroperitoneal laparoscopic partial nephrectomy. Methods From June 2002 to December 2009, 113 cases of renal tumor received retroperitoneal laparoscopic partial nephrectomy. The age ranged from 26 to 73 years. The tumor located in left side in 51 cases and right side in 62 cases with the mean diameter of 3.7 cm(1.2-6.3cm). During the procedure, the renal artery was separated and then clamped with bulldog. The renal parenchymal was incised with cold endoscissor and the tumor was totally removed. Pelvicalyceal repairing and parenchymal hemostasis were then performed. Renal defect closure was achieved with running suture or horizontal mattress suture. Results All the procedures were completed successfully.There was no open conversion. The mean operation time was 85 min(60- 125 min), the mean warm ischemic time was 24 min(19-43 min). The pathology studies revealed 87 cases of clear cell carcinoma, 9 cases of papillary renal cell carcinoma, 7 cases of chromophobe cell carcinoma, 6 cases of perivascular epithelioid renal cell tumor and 4 cases of renal oncocytoma. The surgical margin was negative in all cases. There was no complication of urine leakage. Gross hematuria occurred in 2 cases.During 3-41 months of following up, there was no recurrence. Conclusion Retroperitoneal laparo-scopic partial nephrectomy is safe and effective for the treatment of renal tumor, which becomes an alternative treatment to open procedure.

To study the methylation in the promoter of LRP15 gene and its relationship with gene expression and to explore the possible mechanism of regulating LRP15 gene methylation, the methylation in the promoter of LRP15 gene in K562 cell line was detected by MS-PCR. Then K562 was exposed to 5-aza-2'-deoxycytidine (CdR) and trichostatin (TSA), to determine whether the silencing of LRP15 gene by de novo methylation could be reversed. As a result, it was confirmed by MS-PCR that the promoter of LRP15 was hypermathylated in K562 cell line, and lost its transcription activity. After CdR, with or without TSA, the silencing of LRP15 gene by de novo methylation can be reversed. Observation demonstrated that the expression of LRP15 was controlled by methylation in its promoter in K562. It is suggested that methyltransferase inhibitor and deacetylase inhibitor may be effective agents in leukemia therapy.
Azacitidine ; analogs & derivatives ; pharmacology ; DNA Methylation ; DNA Modification Methylases ; antagonists & inhibitors ; Enzyme Inhibitors ; pharmacology ; Gene Expression Regulation ; drug effects ; Histone Deacetylase Inhibitors ; Humans ; Hydroxamic Acids ; pharmacology ; K562 Cells ; Neoplasm Proteins ; biosynthesis ; genetics ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic ; genetics