This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
Animals ; Chlorzoxazone ; metabolism ; Chromatography, Liquid ; Cytochrome P-450 Enzyme System ; metabolism ; Depression ; Dextromethorphan ; metabolism ; Liver ; enzymology ; Midazolam ; metabolism ; Omeprazole ; metabolism ; Rats ; Stress, Physiological ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; Tolbutamide ; metabolism

OBJECTIVETo compare the short-term outcomes in patients with esophageal cancer after subtotal esophagectomy via thoracoscopy in prone position and in left lateral position.

METHODSBetween September 2008 and September 2010, thoraco-laparoscopic esophagectomy (TLE) with thoracoscopic mobilization of the esophagus and mediastinal esophagectomy was performed in 41 patients in prone position (group A) and other 41 patients (group B) performed by the same surgeon in left lateral position.

RESULTSPreoperatively, the endoscopic location of the tumor was in the upper third in 5 cases (2 vs. 3), the middle third in 21 cases (12 vs. 9), and the lower third in 56 cases (27 vs. 29). The median operative time was 230 (range 170-310) min in group A and 280 (range 190-380) min in group B (P=0.04). The median intraoperative blood loss was 275 (range 100-320) ml in group A and 360 (range 120-670) ml in group B (P=0.09). The median number of lymph nodes dissected was 8.4 (range 4-23) in group A and 6.9 (range 6-21) in group B (P=0.03). The postoperative complications totaled 6 (14.6%) in group A and 8 (17.1%) in group B (P=0.44). After a median follow-up period of 15.7 (range 2-28) months for group A and 16.3 (range 3-31) months for group B, 19 patients in group A died and 21 patients in group B.

CONCLUSIONSFor esophageal cancer under T3N1M0, surgical outcomes are similar between prone thoracoscopic esophageal mobilization and left lateral position. Prone position may be associated with better lymph node dissection.

Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prone Position ; Retrospective Studies ; Thoracoscopy ; methods ; Treatment Outcome

Background: Sentinel lymph node (SLN) mapping has been recommended as an alternative staging approach to lymphadenectomy for apparent uterine-confined endometrial cancer (EC). However, the prognostic value of SLN mapping alone instead of systematic lymphadenectomy on EC patients remains unclear. Methods A multi-center, open label, non-inferiority randomized controlled trial has been designed to identify if SLN mapping alone is not inferior to pelvic lymphadenectomy on prognosis of patients with intermediate-high-risk EC clinically confined to uterus. Eligible patients will be 1:1 randomly assigned to accept SLN mapping or pelvic lymphadenectomy. The primary endpoint is the 2-year progression-free survival (PFS). The second points are the 5-year PFS, 5-year overall survival, surgery-related adverse events and life quality. A total of 780 patients will be enrolled from 6 hospitals in China within 3-year period and followed up for 5 years.

OBJECTIVETo explore the role of Notch signaling in human breast cancers, the expression of Notch1 and its ligand JAG1 in human breast cancers and their relationships with clinical stages of breast cancers were analyzed.

METHODSRT-PCR was used to detect the expression of Notch1 and JAG1 in 62 breast cancer specimens and 22 normal breast tissues at the margin of tumor sections, and the statistical difference of expression rates and standardized coefficient between the two groups were analyzed. To compare the expression intensity of Notch1 and JAG1 at different development stages of the illness and at different stages with or without axillary node metastasis.

RESULTSThe expression rate and standardized coefficient of Notch1 in human breast cancers were significantly higher than those of normal breast tissues at the margin of tumor sections. The expression rate of JAG1 in human breast cancers was 15%, while JAG1 was not detected in normal breast tissues at the margin of tumor sections. The standardized coefficient of Notch1 in cases with axillary node metastasis was significantly higher than that in cases without axillary node metastasis. The standardized coefficient of Notch1 at stage I was significantly lower than that at stage II, and stage II was significantly higher than stage III. There was no statistically significant difference between stage I and stage III.

CONCLUSIONNotch1 and JAG1 are highly expressed in human breast cancers, indicating that the aberrant expression and activation of Notch1 may be related with tumorigenesis of human breast cancer. Notch1 may play different roles at different developmentl stages of human breast cancer.

Adult ; Aged ; Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; pathology ; Calcium-Binding Proteins ; genetics ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Jagged-1 Protein ; Lymphatic Metastasis ; Membrane Proteins ; genetics ; Middle Aged ; Neoplasm Staging ; Receptor, Notch1 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Serrate-Jagged Proteins ; Signal Transduction ; genetics

BACKGROUNDTubulointerstitial renal fibrosis is the common end point of progressive kidney diseases, and tubular epithelial-myofibroblast transdifferentiation (TEMT) plays a key role in the progress of tubulointerstitial renal fibrosis. Anaphylatoxin C3a and C5a are identified as novel profibrotic factors in renal disease and as potential new therapeutic targets. The aim of this study was to investigate whether C3a, C5a can regulate TEMT by transforming growth factor-β1 (TGF-β)/connective tissue growth factor (CTGF) signaling pathway and the effects of C3a and C5a receptor antagonists (C3aRA and C5aRA) on C3a- and C5a-induced TEMT.

METHODSHK-2 cells were divided into C3a and C5a groups which were subdivided into four subgroups: control group, 10 ng/ml TGF-β1 group, 50 nmol/L C3a group, 50 nmol/L C3a plus 1 µmol/L C3aRA group; control group, 10 ng/ml TGF-β1 group, 50 nmol/L C5a group, 50 nmol/L C5a plus 2.5 µmol/L C5aRA group. TGF-β1 receptor antagonist (TGF-β1RA) 10 µg/ml was used to investigate the mechanism of C3a- and C5a-induced TEMT. Electron microscopy was used to observe the morphological changes. Immunocytochemistry staining, real-time PCR and Western blotting were used to detect the expressions of a smooth muscle actin (α-SMA), E-cadherin, Col-I, C3a receptor (C3aR), C5aR, CTGF and TGF-β1.

RESULTSHK-2 cells cultured with C3a and C5a for 72 hours exhibited strong staining of α-SMA, lost the positive staining of E-cadherin, and showed a slightly spindle-like shape and loss of microvilli on the cell surface. The expressions of α-SMA, E-cadherin, Col-I, C3aR, C5aR, TGF-β1 and CTGF in C3a- and C5a-treated groups were higher than normal control group (P < 0.05). C3aRA and C5aRA inhibited the expressions of α-SMA, Col-I, C3aR, C5aR, and up-regulated the expression of E-cadherin (P < 0.05). TGF-β1 and CTGF mRNA expressions induced by C3a and C5a were partly blocked by TGF-β1RA (P < 0.05).

CONCLUSIONC3a and C5a can induce TEMT via the up-regulations of C3aR and C5aR mRNA and the activation of TGF-β1/CTGF signaling pathway in vitro.

Blotting, Western ; Cadherins ; genetics ; Cell Line ; Cell Transdifferentiation ; drug effects ; Complement C3a ; pharmacology ; Complement C5a ; pharmacology ; Epithelial Cells ; cytology ; drug effects ; ultrastructure ; Humans ; Immunohistochemistry ; Microscopy, Electron, Scanning ; Myofibroblasts ; cytology ; drug effects ; ultrastructure ; Real-Time Polymerase Chain Reaction

OBJECTIVETo investigate the expression level of SOX11 mRNA in mantle cell lymphoma (MCL) and other B-cell non-Hodgkin lymphoma (B-NHL) and its prognostic value in MCL.

METHODSThe expression level of SOX11 mRNA in 80 B-NHL patients were determined by real-time quantitative RT-PCR, GAPDH was used as internal control. The dispersion of SOX11 expression ratio of groups with different prognostic factors was described by Mann-Whitney U test.

RESULTSThe SOX11 mRNA expression level was 2.90 (0.75 - 4.63) in 80 B-NHL patients, and the expression level was significantly higher in MCL than that in other B-NHL (P = 0.014). The SOX11 expression level was statistically lower in the group of MCL with hyperleukocytosis, 12 trisomy, MYC amplification and therapeutic effect < PR (P = 0.042, 0.013, 0.028, 0.009) than that of MCL in other group. But SOX11 expression was not associated with MCL international prognostic index (MIPI) (P = 0.333), lactate dehydrogenase (LDH) (P = 0.790), ATM mutation (P = 0.865) and P53 deletion (P = 0.116). The progression free survival (PFS) and overall survival (OS) were significantly longer in the MCL patients with high level of SOX11 than that of other MCL patients.

CONCLUSIONThere was statistically significant differences in SOX11 mRNA expression between MCL with other B-NHL. SOX11 maybe a good prognostic factor in MCL.

Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression ; Humans ; Lymphoma, Mantle-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Non-Hodgkin ; genetics ; pathology ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics ; SOXC Transcription Factors ; genetics ; metabolism

OBJECTIVETo investigate and compare the effectiveness and safety of 80-W GreenLight laser vaporization and GreenLight high-performance system (HPS) 120-W laser vaporization for the treatment of benign prostatic hyperplasia (BPH) in high-risk patients.

METHODSWe allocated 290 high-risk patients with BPH to two groups to receive 80-W (n = 220) and HPS 120-W GreenLight laser vaporization (n = 70). We recorded and compared the pre-, intra- and post-operative clinical data of the two groups.

RESULTSThe operations were successful in both of the groups. There were statistically significant differences in the prostate volume, IPSS, Qmax and PVR before and after surgery (P < 0.01), but not between the two groups (P > 0.05). The operation time, lasing time and energy consumption were (56.5 +/- 22.6) min, (31.2 +/- 10.3) min and (159.8 +/- 29.0) kJ in the 80-W group, as compared with (45.1 +/- 20.4) min, (24.6 +/- 8.3) min and (134.2 +/- 23.3) kJ in the 120 W group, with significant differences between the two (P < 0.01).

CONCLUSIONGreenLight laser vaporization of the prostate is a safe and effective procedure for the treatment of BPH, and the new HPS 120-W laser therapy, with its advantages of easier operation and shorter surgical time, is an even better minimally invasive option for elderly high-risk patients.

Aged ; Aged, 80 and over ; Humans ; Laser Therapy ; adverse effects ; methods ; Male ; Prostatic Hyperplasia ; surgery ; Treatment Outcome

Gastric cancer (GC) is one of the most frequent malignant tumors. In order to systematically characterize the cellular and molecular mechanisms of intestinal GC development, in this study, we used 22 K oligonucleotide microarrays and bioinformatics analysis to evaluate the gene expression profiles of GC in 45 tissue samples, including 20 intestinal GC tissue samples,20 normal appearing tissues (NATs) adjacent to tumors and 5 noncancerous gastric mucosa tissue samples. These profiles allowed us to explore the transcriptional characteristics of GC and determine the change patterns in gene expression that may be of clinical significance. 1519 and 1255 differentially- expressed genes (DEGs) were identified in intestinal GC tissues and NATs, respectively, as determined by Bayesian analysis (P < 0.001). These genes were associated with diverse functions such as mucosa secretion, metabolism, proliferation, signaling and development, which occur at different stages of GC development.

OBJECTIVETo explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.

METHODSTwenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.

RESULTSIn one pedigree, the proband and her mother were found carrying the most common nt3243 A --> G mutation and another 16S rRNA 3205C --> T mutation. But only 3205C --> T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --> G(TAT --> TGT) mutation was explored in another proband with deafness and her affected family members.

CONCLUSION16SrRNA 3205C --> T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --> G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --> Cys) and is co-segregated with diabetes, it may be diabetogenic.

Adult ; Asian Continental Ancestry Group ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; RNA, Ribosomal, 16S ; analysis ; genetics