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CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA-N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. albicans) at a concentration of

Candida species (Candida spp.) are important fungal pathogens, which cause numerous clinical diseases associated with significant mortality and morbidity in healthcare settings. In our previous study, we identified a recombinant peptide, chromogranin A (CGA)-N46, corresponding to the N-terminal Pro31-Gln76 sequence of human CGA, that exhibited antifungal activity against Candida albicans. The present study investigated the antifungal activity of CGA-N46, and its underlying mechanism, against numerous Candida spp. CGA-N46 inhibited the growth of all of the tested Candida spp., of which Candida krusei exhibited the greatest sensitivity. CGA-N46 was able to disrupt the stability of the phospholipid monolayer without damaging the integrity and permeability of the outer membrane of C. krusei cells, and induced cytoplasm vacuolization and mitochondrial damage. In addition, treatment of C. krusei with CGA-N46 was associated with decreased levels of intracellular reactive oxygen species, a reduction in the mitochondrial membrane potential, and DNA synthesis inhibition. The results of the present study suggested that CGA-N46 was able to pass through the cell membrane of Candida spp. by temporarily destabilizing the phospholipid membrane, which in turn led to mitochondrial dysfunction and inhibition of DNA synthesis. Therefore, CGA-N46 may be considered a novel antifungal compound for the treatment of patients with C. krusei infections.

Objective To investigate the effects of HMG-CoA reductase inhibitor rosuvastatin on atherosclerosis and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and nuclear factor (NF)-κB p65 expressions in apolipoprotein E (ApoE)-deficient mice. Methods Twenty six-week-old ApoE-deficient male mice were randomly divided into hyperlipidemia model group (n=10) and rosuvastatin group (n=10), and they were fed high-fat diet for 13 weeks. Ten six-week-old C57BL/6J (wild type, WT) male mice were selected as normal control group, and were fed normal diet for 13 weeks. After 13 weeks, blood was drawn from the mice to determine serum levels of total cholesterol (TCH), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C). These mice were sacrificed, and their aortas were obtained and examined with HE staining; Western blotting and RTPCR were used to analyze LOX-1, NF-κB p65 expression intensity in aorta tissue quantitatively. Results The serum level of TCH, TG and LDL-C in rosuvastatin group were lower than those in hyperlipidemia model group (P

The Cu2O/TiO2heterostructure nanocomposites photocatalysts with different molar ratios of Cu2+/Ti4+were successfully synthesized by a simple hydrothermal procedure. The obtained samples were characterized by XRD, SEM, UV-vis DRS in order to detect the composition, the shape and the property. The photocatalytic activity of Cu2O/TiO2nanocomposites was evaluated by the degradation of methyl orange (MO) as a model compound. The experimental results showed that the prepared Cu2O/TiO2nanocomposites exhibited higher photocatalytic activity for the degradation of MO than the pure Cu2O and the commercial anatase TiO2under visible light irradiation.

Permanent Magnet Synchronous Motor(PMSM) is a multivariable, nonlinear system with strong couple. It’s sensitive to the parameters and load variations. To improve the system static, dynamic performance and robustness, the fractional-order PIλ control strategy is proposed. Compared with integer-order PI controller, the fractional-order PIλ controller achieves better control performance due to an extra adjustable knob λ. The simulation results show that the fractional-order PIλ controller can track the given speed quickly and accurately, and has better anti-interference with load variation.

This paper studies the dynamics of a duopoly model with bounded rationality and nonlinear demand function. Based on the stability theorem and Jurys criterions, we prove that the model has two unstable boundary fixed points and a local stable Nash equilibrium. Then we depict the stability region of Nash equilibrium, and investigate the effects of output adjustment speed on the players profit respectively. Theoretical analysis and simulations show that higher output adjustment speed can result in chaotic variation of outputs, and that the Nash equilibrium is the optimal result of duopoly game. To improve the profitability of each player and achieve the optimal game result, we put forth a new scheme combined with the time-delayed feedback control and the limiter control to stabilize the output to Nash equilibrium. Finally, the numerical simulation is adopted to verify the effectiveness and feasibility of the above control scheme.

Based on the analysis of thickness control theory, a controller combined fuzzy neural network with intellectual integration was designed in consideration of the nonlinear, large time delay, varying time characteristics of tandem cold mill thickness control. The controller adopted three layers BP network to realize fuzzy control and linked with intelligent integration in parallel for forming a three-dimensional full intelligent composite controller which enables the cold tandem rolling thickness fuzzy neural network control based on intelligent integration. Simulation results show that, compared with the conventional PID control, the compound intelligent control strategy can remarkable improved performance of control system of cold tandem rolling thickness.

The aim of the present study was to explore mechanisms underlying the effects of down-regulating β-catenin expression on esophageal carcinoma (EC) cells.Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1/2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry.Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P0.05), with no significant difference among the three groups with regard to apoptosis (P0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating β-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P0.05). At the same time, the PCNA labeling index was decreased accordingly (P0.05).Inhibition of EC Eca-109 cellproliferation by down-regulating β-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).

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.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.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(P0.05). The doses of propofol were higher in the standard clinical practice group than in the Narcotrend group [(460+/-30) mg vs. (380+/-35) mg, P0.01]. 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, P0.01; (12.2+/-3.5) min vs. (6.6+/-3.2) min, P0.01, respectively]. There was no difference in the dosage of fentanyl, VAS, or the incidence of postoperative nausea or vomiting between the two groups (P0.05).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.

Aims: The fragile histidine triad (FHIT) gene is frequently inactivated in human cancers; however, the FHIT gene remains unexplored in Hodgkin's lymphoma. The aim of this study was to investigate the role of FHIT expression in classical Hodgkin's lymphoma.Methods: Classical Hodgkin's lymphomas were analysed for FHIT gene expression by two‐step non‐biotin immunohistochemical method and Western blotting.Results: Thirty of the 33 (91%) cases of Hodgkin's lymphoma tested were positive for FHIT protein by immuohistochemistry. The expression of FHIT was mainly located in cytoplasm of Reed–Sternberg (HRS) cells. The protein expression was also documented by Western blotting. The non‐Hodgkin's lymphomas were negative for FHIT protein.Conclusions: The results indicate that abnormal FHIT expression is noted frequently in classical Hodgkin's lymphoma and the expression can give insight into the pathogenesis of the disease. The protein may serve as a marker to localise HRS cells in classical Hodgkin's lymphoma.

Candida species (Candida spp.) are important fungal pathogens, which cause numerous clinical diseases associated with significant mortality and morbidity in healthcare settings. In our previous study, we identified a recombinant peptide, chromogranin A (CGA)-N46, corresponding to the N-terminal Pro31-Gln76 sequence of human CGA, that exhibited antifungal activity against Candida albicans. The present study investigated the antifungal activity of CGA-N46, and its underlying mechanism, against numerous Candida spp. CGA-N46 inhibited the growth of all of the tested Candida spp., of which Candida krusei exhibited the greatest sensitivity. CGA-N46 was able to disrupt the stability of the phospholipid monolayer without damaging the integrity and permeability of the outer membrane of C. krusei cells, and induced cytoplasm vacuolization and mitochondrial damage. In addition, treatment of C. krusei with CGA-N46 was associated with decreased levels of intracellular reactive oxygen species, a reduction in the mitochondrial membrane potential, and DNA synthesis inhibition. The results of the present study suggested that CGA-N46 was able to pass through the cell membrane of Candida spp. by temporarily destabilizing the phospholipid membrane, which in turn led to mitochondrial dysfunction and inhibition of DNA synthesis. Therefore, CGA-N46 may be considered a novel antifungal compound for the treatment of patients with C. krusei infections.

To investigate the effects of different anesthesia methods on immune surveillance and tumor metastasis in tumor-bearing rats.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.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 (P0.05 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 (P0.05 or 0.01).Neuraxial block provides protection of the activity of immune surveillance and reduces tumor metastases in tumor-bearing rats compared with general anesthesia.

Some researches found that the intensity, property and management of acute pain are associated with chronic pain in tumor patients after thoracotomy. Chronic pain may be transformed from acute pain. However, there are no routine or standard strategies to effectively prevent or relieve chronic pain in tumor patients after thoracotomy. This study was to explore the correlation of acute and chronic pain in tumor patients after thoracotomy.A total of 105 patients (American Society of Anesthesiologists physical status I-II) underwent thoracotomy were randomly divided into 3 groups: 36 received administration of ropivacaine and morphine through thoracic epidural preoperatively (group PE), 36 received the same treatment postoperatively (group E), and 33 received intravenous infusion of fentanyl postoperatively (group IV). VAS scores were recorded in the first 48 h after operation. The occurrence of chronic pain was observed at the first, second, third, sixth months after operation.VAS scores in the first 48h after operation were significantly lower in group PE and group E than that in group IV (P0.05). VAS scores were significantly lower in group PE than in group E (P=0.004 at 4 h, P=0.013 at 8 h, P=0.035 at 24 h). The occurrence rate of pain after operation was significantly lower in group PE than in groups E and IV in the first and second months (Chi2=5.989, P=0.014; Chi2=7.603, P=0.006), and lower in groups PE and E than in group IV in the third and sixth months (Chi2=6.585, P=0.010; Chi2=8.661, P=0.003). The duration of pain was significantly shorter in group PE than in groups E and IV (P=0.027, P=0.009).Chronic pain after thoracotomy is associated with the intensity and management of acute pain after thoracotomy. The patients with intensive acute pain would experience intensive and long-term chronic pain. Preemptive administration with thoracic epidural ropivacaine and morphine can decrease the incidence and duration of chronic pain after operation.

To investigate the protective effects of different concentrations of ketamine against acute lung injury induced by lipopolysaccharide (LPS) in rats and its mechanism.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.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 (P0.01). 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.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.

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

Hilar cholangiocarcinoma is associated with low resectability and poor survival. The aim of this study was to evaluate the roles of matrix metalloproteinases-2 (MMP-2) and its tissue inhibitor of metalloproteinase-2(TIMP-2) in tumor invasion or as a prognostic factor in patients with human hilar cholangiocarcinoma.The expressions of MMP-2 and TIMP-2 were investigated in patients. Paraffinized tissue sections obtained from 50 patients with human hilar cholangiocarcinoma were analysed. The expressions of MMP-2 and TIMP-2 were examined immunohistochemically. Image analysis with image-pro plus analysis software was used to semiquantitatively determine the ratio of MMP-2 to TIMP-2.The expression levels of MMP-2 and TIMP-2 were strongly associated with tumor hepatic invasion in patients with hilar cholangiocarcinoma. Significant differences in the ratio of MMP-2 to TIMP-2 between some pathologic factors were observed in patients with hilar cholangiocarcinoma.MMP-2 plays an essential role in tumor invasion and metastasis, while TIMP-2 is shown to strongly inhibit cancer invasion and metastasis. The ratio of MMP-2 to TIMP-2 may be a prognostic indicator for patients with hilar cholangiocarcinoma.

AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers, but little is known about its expression in human hepatocellular carcinogenesis and evolution. METHODS: Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression. RESULTS: All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83 (65.0%) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue were highly significant (P = 0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P = 0.219); (b) in tumors with higher clinical stage III and IV (91.3%, P = 0.000), compared with tumors with lower stage I and II (27.6%); and (c) in cancers with bigger tumor size (> 50 mm) (75.0%, P = 0.017), compared with smaller tumor size (≤ 50 mm). CONCLUSION: FHIT inactivation seems to be both an early and a later event, associated with carcinogenesis and progression to more aggressive hepatocellular carcinomas. Thus, evaluation of Fhit expression by immunohistochemistry in hepatocellular carcinoma may provide important diagnostic and prognostic information in clinical application.

Telomerase activity has been detected in a broad range of human cancers including epithelial malignancies from in female genital tract, but the expression of the telomerase activity in ovarian sex-cord tumors has not been reported up to now. In this report we investigated the telomerase activity in ovarian sex-cord stromal tumors and its relationship with clinicopathological feature.Twenty-five cases of ovarian sex-cord stromal tumor, including granulosa cell tumors, thecofibromas, sclerosing stromal tumors, and Sertoli-Leydig cell tumors were retrieved, and the expression of human telomerase reverse transcriptase (hTRT) was assessed immunohistochemically using polyclonal antibody H231.hTRT were positive in 60.0% of all cases, and the signal mainly located in the cytoplasm of tumor cells, especially in luteinized cells and Ledig cells. The positive rate was significantly related to different histological types and the patients' clinical endocrinal manifestation (P value were 0.01 and 0.041, respectively), but no statistically significant difference was found between the expression of hTRT and tumor histological grade or patients' prognosis.In ovarian sex-cord stromal tumors, the tumor component differentiating to luteinized stromal cell has high telomerase activity, and the telomerase activity may play an important role in patients' endocrinal disorder.

AIM: To investigate the expression of fragile histidine triad (FHIT) protein, and the possible relationship between FHIT expression and clinicopathological indices in gastric carcinoma. METHODS: FHIT protein expression was examined in 76 cases of gastric carcinoma, 58 cases of intraepithelial neoplasia, and 76 cases of corresponding normal mucosae by immunohistochemical method to analyze its relationship to histological grade, clinical stage, metastatic status and prognosis. RESULTS: The FHIT protein expression was positive in 28/76 (36.8%) cases of adenocarcinoma tissue, 22/58 (37.9%) cases of adjacent dysplastic tissue and 76/76 (100%) cases of distal normal gastric mucosa. There was a significant difference in the expression of FHIT protein between cancer or adjacent intraepithelial neoplasia and normal gastric mucosa (P = 0.000). FHIT protein expression was found in 64.3% (18/28) of grades I and II cancers, and 20.8% (10/48) of grade III cancers (P = 0.000), in 56.3% (18/32) of stages I and II cancers and 22.7% (10/44) of stages III and IV cancers (P = 0.004), and in 63.6% (14/22) of cancers without metastasis but only 25.9% (14/54) of those with metastasis (P = 0.003). The significant difference in the expression of FHIT was found between histological grade, clinical stage and metastatic status of cancer. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of FHIT (71 mo) and those without (33 mo, log rank = 20.78, P = 0.000). CONCLUSION: FHIT protein is an important tumor suppressor protein. Loss of FHIT protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis of gastric adenocarcinoma.

The next decade (1985-95) in the Republic of China (R.O.C.) on Taiwan will prove to be a period of great significance, primarily for two reasons. First, its economy will undergo important structural changes which, if successfully accomplished, will probably enable the R.O.C. on Taiwan to achieve the status of a full-fledged developed country by the end of the century. Second, the R.O.C. on Taiwan will face several major challenges and crises on such issues as leadership succession, further democratization, and unification with the mainland.