Effects of DACT2 on epithelial mesenchymal transition of glioma cells and its potential mechanism / 西安交通大学学报(医学版)

Objective: To investigate the effects and potential mechanism of tumor suppressor dishevelled-binding antagonist of beta-catenin 2 (DACT2) on epithelial-mesenchymal transition of glioma cells. Methods: The expressions of DACT2 in glioma cells U87, U251, A172 and SHG44 were detected by RT-PCR after 5-Aza treatment. The methylation status of DACT2 promoter was detected by methylation specific PCR (MSP). Western blot was used to detect the expression of DACT2 protein. U87 cells overexpressing DACT2 were constructed and verified by Western blot. Transwell assay was used to detect cell migratory and invasive ability. The protein levels of E-cadherin, Vimentin, MMP2 and Wnt/β-cadherin pathway proteins, i.e., active-β-cadherin, p-β-cadherin and total β-cadherin, in cells were detected by Western blot. Results: DACT2 expression was observed in all these cells after 5-Aza treatment; untreated U87 and U251 cells did not express DACT2 while A172 and SHG44 cells showed weak expression. The DACT2 promoter was completely methylated in U87 and U251 cells, and partially methylated in A172 and SHG44 cells. The level of DACT2 in U87 and U251 cells was lower than that in A172 and SHG44 cells (P<0.05). After transfection of pcDNA3.1-DACT2, the expression of DACT2 in U87 cells increased significantly (P<0.05), U87 cells overexpressing DACT2 were successfully constructed. Overexpression of DACT2 could significantly inhibit epithelial-mesenchymal transition, invasion and migration of U87 cells and block Wnt/β-catenin pathway activation (P<0.05). Conclusion: The DACT2 promoter in glioma cells is highly methylated, and the exogenous overexpression of DACT2 can promote the epithelial mesenchymal transition, invasion and migration of U87 cells. The underling mechanism may be related to the regulation of Wnt/β-catenin pathway by DACT2.

Use of the American Experiences for Reference on the Intervention of Pharmacists to Prescribing Behavior in China / 中国药学杂志

OBJECTIVE: To strengthen pharmacist intervention in prescribing behavior of doctors, so as to further standardize prescribing behavior.METHODS: Through the review of the advantages and disadvantages of the relevant laws, education training and assessment system for prescription intervention in the USA, a deep analysis was made in combination with the Chinese system and the characteristics of the medical staff.RESULTS: A new clinical pathway was introduced to standardize the intervention of doctors′ prescriptions, so as to improve the level of diagnosis and treatment and the environment for medical treatment in China.CONCLUSION: Improving pharmacists′ professional accomplishment and introducing Internet model and intelligent medical technology can improve the linkage among clinical, community medical institutions and social pharmacies, and also enhance the feasibility and reliability of Internet prescription drug purchase intervention. Promote the closed-loop connection and continuous upgrading of the pharmaceutical industry chain, gradually realize the standardization model of diagnosis and treatment, and then promote the results of the overall medical level.

Correlation of KRAS gene mutations and clinicopathologic parameters in colorectal carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between KRAS gene mutations and clinicopathological parameters in patients with colorectal carcinoma (CRC).</p><p><b>METHODS</b>PCR-based direct sequencing was used to detect the mutations of KRAS gene and to correlate between clinicopathological characteristics and the presence of various KRAS mutations in 244 cases of CRC.</p><p><b>RESULTS</b>KRAS mutations were identified in 92 cases (37.7%) of CRC. Five types of mutation were detected at codon 12, including G12D (40 cases, 16.4%), G12V (16 cases, 6.6%), G12A (7 cases, 2.9%), G12S (5 cases, 2.0%) and G12C (4 cases, 1.6%). Two types of mutation were detected at codon 13, including G13D (17 cases, 7.0%) and G13C (2 cases, 0.8%). One type of mutation was detected in codon 61, i.e. Q61K (1 case, 0.4%). KRAS mutation rate was higher in females (45.6%, 36/79) than in males (32.1%, 53/165; P < 0.05), but not related to another clinicopathological characteristics.</p><p><b>CONCLUSIONS</b>Female CRC patients have a higher KRAS mutation rate than the male patients. KRAS mutation has no significant correlation with patient's age, tumor site, tumor gross appearance, degree of differentiation, depth of invasion, TNM stages, lymphatic invasion, abdominal or distant metastases and prognosis in this study.</p>

The changes of peripheral blood lymphocyte subsets in patients with acute hydrogen chloride gas poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the changes of peripheral blood lymphocyte subsets in patients with acute hydrogen chloride gas poisoning.</p><p><b>METHODS</b>When the patients were admitted or on the secondary day, the percentages of total T-cell lymphocyte subsets (CD(3)(+)CD(19)(-)), CD(4)(+)T cells (CD(3)(+)CD(4)(+)), CD(8)(+)T cells (CD(3)(+)CD(8)(+)), B cells (CD(3)(-)CD(19)(+)) and NK cells (CD(3)(-)CD(16)(+)CD(56)(+)), and the ration of CD(4)(+)/CD(8)(+) in 37 cases with acute hydrogen chloride gas poisoning and 49 healthy controls were detected with flow cytometer.</p><p><b>RESULTS</b>The total T-cell percentage and total CD(4)(+)T cell percentage in 37 cases were significantly lower than those in 47 controls (P < 0.05). The percentages of NK cells and B lymphocytes in 37 cases significantly increased, as compared with controls (P < 0.05). The ration of CD(4)(+)/CD(8)(+) in 37 cases significantly decreased, as compared with controls (P < 0.05).</p><p><b>CONCLUSION</b>The lymphocyte subsets in the patients with acute hydrogen chloride gas poisoning changed, which could influence the immune function of patients.</p>

Expression and predictive role of excision repair cross complementation group 1, ribonucleotide reductase subunit M1, and β-tubulin 3 in postoperative patients with non-small cell lung cancer receiving adjuvant chemotherapy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the predictive value of excision repair cross complementation group 1 (ERCC1),ribonucleotide reductase subunit M1 (RRM1), and β-tubulin 3 expressions in postoperative patients with stage 1- 3 non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy.</p><p><b>METHODS</b>All NSCLC patients received surgery therapy followed by at least one cycle of adjuvant chemotherapy in our hospital from January 2004 to December 2007. The expressions of ERCC1, RRM1, and β-tubulin 3 were detected by immunohistochemical methods. The relationships among clinicopathologic characteristics, chemotherapy regimens,biomarkers' expressions and disease-free survival (DFS) were analyzed.</p><p><b>RESULTS</b>The high-expression rates of ERCC1, RRM1, and β-tubulin 3 were 36.4%,43.7%,and 38.4%,respectively. The expressions of these three biomarkers were not correlated. After a median follow-up of 35.8 months, 80 patients experienced metastatic or recurrent tumors and 40 patients died. The median overall survival was not reached and the median DFS was 24.1 months. Univariate survival analysis showed that sex, clinical stage,and adenocarcinoma or not were related to DFS, while age, smoke history, chemotherapy regimens, and expression levels of ERCC1, RRM1, and β-tubulin 3 has no prognostic significance in these surgically resected NSCLC patients who were receiving adjuvant chemotherapy. Male (P=0.036), earlier clinical stage (P=0.001), and non-adenocarcinoma (P=0.004) predicted better DFS. Stratified analysis indicated that in RRM1 high-expression strata,the regimens with gemcitabine had curtailed DFS compared with other regimens (P=0.054); in β-tubulin 3 high-expression strata,the regimens containing taxane (including paclitaxel and docetaxel subgroups) had curtailed DFS compared with other regimens (P=0.076), although there was no statistical significance. However,there were no similar predictive significance in RRM1 and β-tubulin 3 low-expression strata or in ERCC1 strata with different expression levels. COX proportional regression analysis showed that adenocarcinoma or not and clinical stage were independent risk factors of DFS in this population.</p><p><b>CONCLUSIONS</b>In postoperative NSCLC patients who are receiving adjuvant chemotherapy, patients with high expression of RRM1 tends to be resistant to gemcitabine and patients with high expression of β-tubulin 3 tends to be resistant to taxane drugs. ERCC1, RRM1, and β-tubulin 3 detected by immunohistochemistry can be biomarkers to help to choose better chemotherapy regimen and predict the effectiveness of adjuvant chemotherapy.</p>

Application of a narcotrend-assisted anesthesia in-depth monitor in the microwave coagulation for liver cancer during total intravenous anesthesia with propofol and fentanyl / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>CT-guided microwave coagulation is a minimally invasive surgery for patients with liver cancer. Total intravenous anesthesia with propofol and fentanyl is commonly used. The depth of anesthesia during microwave coagulation for liver cancer is still monitored by clinical signs. There are few subjective and effective indicators. This study explored the application of Narcotrend-assisted "depth of anesthesia" monitoring on microwave coagulation for patients with liver cancer during total intravenous anesthesia with propofol and fentanyl.</p><p><b>METHODS</b>Forty liver cancer patients underwent CT-guided microwave coagulation were randomly assigned to receive Narcotrend index monitoring or standard clinical monitoring for depth of anesthesia with 20 patients in each group. All patients received total intravenous anesthesia with propofol and fentanyl. The depth of anesthesia for patients in the Narcotrend group was measured according to a Narcotrend index, which was maintained between D2 and E0. The depth of anesthesia for those in the standard clinical practice group was measured according to heart rate, mean arterial pressure, and patient movement. Changes of hemodynamics, the duration of the emergence from anesthesia, and the recovery of orientation were recorded. The doses of propofol and fentanyl, postoperative visual analogue scores (VAS), and the incidence of postoperative nausea and vomiting were also recorded.</p><p><b>RESULTS</b>There was no significant alteration in heart rate or mean arterial pressure between the two groups. Compared with other anesthetic stages, both heart rate and mean arterial pressure decreased during the induction of the anesthesia in the two groups(P<0.05). The doses of propofol were higher in the standard clinical practice group than in the Narcotrend group [(460+/-30) mg vs. (380+/-35) mg, P<0.01]. The duration of emergence and orientation were longer in the standard clinical practice group than in the Narcotrend group [(9.5+/-2.9) min vs. (4.9+/-2.2) min, P<0.01; (12.2+/-3.5) min vs. (6.6+/-3.2) min, P<0.01, respectively]. There was no difference in the dosage of fentanyl, VAS, or the incidence of postoperative nausea or vomiting between the two groups (P>0.05).</p><p><b>CONCLUSION</b>For patients with liver cancer, monitoring the depth of anesthesia with Narcotrend on microwave coagulation can contribute to lower dosage of propofol and shorten duration of recovery during total intravenous anesthesia with propofol and fentanyl.</p>

Effects of neuraxial block and general anesthesia on tumor metastasis in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of different anesthesia methods on immune surveillance and tumor metastasis in tumor-bearing rats.</p><p><b>METHODS</b>Seventy-two Fischer 344 rats were randomly assigned into 3 equal groups and anesthetized for 1 h with ketamine (group K), propofol (group P), or neuraxial block (group B). All the rats were subjected to laparotomy followed by intravenous injection of MADB106 tumor cells, and 24 h after the injection, the number and activity of circulating CD3(+), CD4(+), CD8(+), and D4(+)/CD8(+) lymphocyte subsets and NK cellèCD161a(+)éwere assessed. Three weeks later, the lung metastases were counted.</p><p><b>RESULTS</b>Compared with those in group B, the numbers of CD3(+), CD4(+), CD8(+), and CD161a(+) lymphocytes and the activity of circulating NK cells were significantly reduced, and the lung metastases of MADB106 increased significantly in groups K and P (P<0.05 or 0.01 ). The activity of immune surveillance in group K was significantly lower than that in group P except for CD8(+) cells, and the tumor metastases in group K increased significantly in comparison with those in group P (P<0.05 or 0.01).</p><p><b>CONCLUSION</b>Neuraxial block provides protection of the activity of immune surveillance and reduces tumor metastases in tumor-bearing rats compared with general anesthesia.</p>

Clinicopathologic significance of chromosome 17 polysomy in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological significance of chromosome 17 polysomy in breast cancer.</p><p><b>METHODS</b>Retrospective study of 200 cases of breast cancer including 106 cases of invasive ductal carcinoma and 94 cases of in-situ carcinoma was performed by fluorescence in-situ hybridization (FISH) to explore the relationship between chromosome 17 polysomy and age, nuclear atypia, lymphatic metastasis, HER2 gene amplification and HER2 protein expression.</p><p><b>RESULTS</b>Twenty-six percent (52/200) of chromosome 17 polysomy was detected in 200 cases of breast ductal carcinoma, all of which were invasive ductal carcinoma. Overall 52. 8% (52/180) of invasive ductal carcinoma cases showed chromosome 17 polysomy, which was correlated to HER2 gene amplification (P = 0.000) and HER-2 protein expression (P=0.000), and to HER2 expression combined with HER2 gene amplification (P=0.001). Chromosome 17 polysomy with or without HER2 gene amplification was also associated with high-grade nuclear atypia (P = 0.012 or P = 0.010) and lymphatic metastasis (P = 0.002 or P = 0.009 ). However, chromosome 17 polysomy with or without HER2 gene amplification was not correlative with the age of patients (P = 1. 000 or P = 0. 415).</p><p><b>CONCLUSION</b>Chromosome 17 polysomy may be related to the nuclear atypia, metastasis, HER2 gene amplification of invasive ductal carcinoma and thus a worse prognosis of the patients.</p>

Protective effect of ketamine against acute rat lung injury induced by liopolysaccharide and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effects of different concentrations of ketamine against acute lung injury induced by lipopolysaccharide (LPS) in rats and its mechanism.</p><p><b>METHODS</b>Forty-eight male Wistar rats were randomized into 4 equal groups, namely the control group, LPS group, ketamine group I (5 mg/kg), and ketamine group II (10 mg/kg). The neutrophil count, protein contents in the bronchoalveolar lavage fluid (BALF) and the wet/dry lung weight ratio were measured 4 h after LPS injection. TNF-alpha, IL-8, NO, iNOS and NF-kappaB were also measured in the lung tissues.</p><p><b>RESULTS</b>In LPS group, the neutrophil count, protein contents in BALF, the wet/dry lung weight ratio and the levels of tumor necrosis factor-alpha(TNF-alpha), interleukin-8 (IL-8), and NO were all significantly increased compared with the control group (P<0.01). The mRNA expression of iNOS and the protein expression of NF-kappaB were also increased in LPS groups. Ketamine treatment attenuated the increase in wet/dry lung weight ratio, neutrophil count, and protein contents in BALF in a dose-dependent manner. Ketamine also dose-dependently inhibited the production of TNF-alpha, IL-8 , and NO and lowered iNOS mRNA and NF-kappaB protein expression.</p><p><b>CONCLUSION</b>Ketamine can offer protection against LPS-induced acute lung injury in rats by inhibiting the expression of NF-kappaB and attenuating the production of the inflammatory cytokines.</p>

Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumor: a study of 156 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic significance of various clinicopathologic parameters in gastrointestinal stromal tumor (GIST), and to study the frequency of c-kit exon 11 mutations in this tumor.</p><p><b>METHODS</b>One hundred and fifty-six cases of gastric or small intestinal GIST were retrieved from the archival files of the Department of Pathology, Chinese PLA General Hospital. The clinical features, site of occurrence, tumor diameter, mitotic index, coagulative tumor necrosis, and risk grade were studied and analyzed statistically. Tumor DNA was extracted and c-kit exon 11 was amplified. Upon detection by denaturing high-performance liquid chromatography, the amplified exon 11 was sequenced.</p><p><b>RESULTS</b>For the 83 cases of gastric GIST studied, the mean age of patients was 55.4 years. Follow-up information was available in 62 cases, with 17 cases having local recurrence or distant metastasis. The 5-year survival rate was 66.5% +/- 17.1%. For the 73 cases of small intestinal GIST studied, the mean age of patients was 50.6 years. Follow-up information was available in 43 cases, with 22 cases having local recurrence or distant metastasis. The 5-year survival rate was 61.8% +/- 18.3%. In general, for gastric GIST, age younger than 50 years (P = 0.046), advanced clinical stage (P = 0.0001), large tumor size (P = 0.0001), high mitotic index (P = 0.0001), presence of coagulative tumor necrosis (P = 0.0001), and high risk grade (P = 0.004) were associated with lower survival rate. COX hazard proportional model revealed that advanced clinical stage (P = 0.001), large tumor size (P = 0.001), high mitotic index (P = 0.002) and high risk grade (P = 0.018) indicated worse prognosi. For small intestinal GIST, advanced clinical stage (P = 0.010) and presence of coagulative tumor necrosis (P = 0.036) were associated with lower survival rate. Advanced clinical stage was an independent prognostic factor. A total of 25 cases harbored c-kit mutations. The frequency of c-kit mutations was 32% and 22.5% for gastric and small intestinal GIST respectively. For gastric GIST, c-kit mutations occurred mainly in patients older than 50 years. In contrast, c-kit mutations in small intestinal GIST occurred in the age group of 40 to 49 years.</p><p><b>CONCLUSIONS</b>For gastric GIST, advanced clinical stage, tumor diameter, mitotic index and risk grade are the main prognostic indicators. For small intestinal GIST, advanced clinical stage and presence of coagulative tumor necrosis indicate poor prognosis. In general, small intestinal GIST is more frequently associated with metastasis and tumor relapse than gastric GIST. The occurrence of c-kit mutations also correlates with age of patients.</p>

Expression of fragile histidine triad (FHIT) protein and its significance in diagnosing classical Hodgkin lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of FHIT protein and its potential application in diagnosing classic Hodgkin lymphoma.</p><p><b>METHODS</b>Immunohistochemical study using EnVision method for FHIT tumor suppressor protein, hematopoietic stem cell markers CD133/AC133 and CD34, B-cell marker CD20, T-cell marker CD3 and oncoprotein c-erbB2 was performed on 33 cases of classic Hodgkin lymphoma.</p><p><b>RESULTS</b>Thirty-three of the Hodgkin lymphoma cases (90.9%) expressed FHIT protein. The antigen was mainly located in the cytoplasm, nucleus and membrane of classic Reed-Sternberg and Reed-Sternberg-like cells. Normal B and T lymphocytes, as well as their malignant counterparts, were negative for FHIT protein; whereas monocytes, histiocytes and dendritic cells were positive. All the cases studied were negative for CD133/AC133, CD34, CD3 and c-erbB-2. Two of the 33 cases showed positive staining for CD20 in some of the Reed-Sternberg cells.</p><p><b>CONCLUSION</b>The expression of FHIT protein can be used as a useful adjunct in diagnosing classic Hodgkin lymphoma.</p>

Diagnosis of human papillomavirus infection in paraffin-embedded cervical tissues by gene clip technology / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the feasibility of diagnosing of human papillomavirus (HPV) infection in paraffin-embedded cervical tissues by high-throughput gene chip technology and its clinical significance.</p><p><b>METHODS</b>Forty cases of HPV-related cervical lesions, including 18 cases of invasive squamous cell carcinoma, 12 cases of cervical intraepithelial neoplasia (CIN) III, 6 cases of CIN II and 4 cases of CIN I, were enrolled. DNA was extracted from paraffin-embedded tissues and amplified by polymerase chain reaction (PCR) using HPV DNA primers. The PCR products were then reversely hybridized with gene chip technology. The results were compared with that of in-situ hybridization (ISH).</p><p><b>RESULTS</b>All of the 18 cases of cervical squamous cell carcinoma were positive for high-risk HPV genotypes (with 1 case showing a mixture with low-risk genotypes). In contrast, 11 cases (91.7%) of CIN III, 5 cases (83%) of CIN II and none of the CIN I cases were positive for high-risk HPV genotypes. On the other hand, low-risk HPV genotypes were detected only in 1 case (17%) of CIN II and 2 cases (50%) of CIN I. The difference between the two groups (CIN III/squamous cell carcinoma versus CIN I/CIN II) was statistically significant (U = 80.0, P < 0.01). Among the 10 squamous carcinoma cases positive for HPV types 16 and 18 by gene chip technology, high-risk HPV DNA was also detected in 6 of them when using in-situ hybridization.</p><p><b>CONCLUSIONS</b>Gene chip technology is able to detect multiple HPV genotypes in paraffin-embedded tissues with high sensitivity and specificity. The distinction between low and high-risk HPV genotypes is seemed useful in prevention and management of cervical cancer.</p>

Significance of MMP2 and MMP9 expression in prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the significance of the expression of matrix metalloproteinases (MMPs) in prostate cancer (PCa) and its clinical association.</p><p><b>METHODS</b>Fifty one cases of PCa and 10 cases of BPH were studied by immunohistochemical method using monoclonal antibodies to MMP2 and MMP9.</p><p><b>RESULTS</b>There was significant correlation between MMP2 or MMP9 and pathological grade, Gleason score and PCa metastasis.</p><p><b>CONCLUSION</b>The expression of MMP2 and MMP9 may play an important role in the development and metastasis of PCa.</p>