CT-based radiomics scores predict response to neoadjuvant chemotherapy and survival in patients with gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients' responses vary. We aimed to develop and validate a radiomics score (rad_score) to predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification. METHODS: A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared. RESULTS: In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC [95% CI] =0.82 [0.67, 0.98]), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 [0.42, 0.83], P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 [0.51, 0.88], P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P < 0.001). CONCLUSION: The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.

Hispidulin mediates apoptosis in human renal cell carcinoma by inducing ceramide accumulation.

Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Hispidulin (10, 20 µmol/L) decreased the viability of ccRCC cells in dose- and time-dependent manners without affecting that of normal tubular epithelial cells. Moreover, hispidulin treatment dose-dependently increased the levels of cleaved caspase-8 and caspase-9, but the inhibitors of caspase-8 and caspase-9 only partly abrogated hispidulin-induced apoptosis, suggesting that hispidulin triggered apoptosis via both extrinsic and intrinsic pathways. Moreover, hispidulin treatment significantly inhibited the activity of sphingosine kinase 1 (SphK1) and consequently promoted ceramide accumulation, thus leading to apoptosis of the cancer cells, whereas pretreatment with K6PC-5, an activator of SphK1, or overexpression of SphK1 significantly attenuated the anti-proliferative and pro-apoptotic effects of hispidulin. In addition, hispidulin treatment dose-dependently activated ROS/JNK signaling and led to cell apoptosis. We further demonstrated in Caki-2 xenograft nude mice that injection of hispidulin (20, 40 mg·kg-1·d-1, ip) dose-dependently suppressed tumor growth accompanied by decreased SphK1 activity and increased ceramide accumulation in tumor tissues. Our findings reveal a new explanation for the anti-tumor mechanisms of hispidulin, and suggest that SphK1 and ceramide may serve as potential therapeutic targets for the treatment of ccRCC.

Unusual calcifying fibrous tumor in the fallopian tube: review and discussion of the differential diagnosis.

Calcifying fibrous tumor (CFT) is a rare benign soft tissue tumor of unknown etiology and extremely rare in female reproductive system. We present a case of unusual CFT in the ampulla of fallopian tube occurring in a middle-aged female patient with multiple uterine leiomyomas. A hysterectomy was performed on a 48-year-old woman for uterine leiomyomas. At surgery, a solitary, well-defined nodule, measuring 1.0 cm in diameter, was incidentally observed on the wall of ampulla of right fallopian tube. The lesion of fallopian tube was resected totally. Histologically, this lesion was unencapsulated and composed of hyalinized collagenous fibrous tissue with psammomatous calcification and focal lymphoplasmacytic infiltrate. Sparsely fibroblast-like spindle cells were scattered in the dense hyalinized background with bland nuclei. By immunohistochemistry, vimentin was diffusely positive in most cells, and a focal reactivity for CD34 was also observed in spindle cells. However, they were negative for cytokeratin (AE1/AE3), S-100 protein, CD117, DOG1, SMA, desmin, and ALK. The Ki-67 labeling index of the lesion was <1%. A diagnosis of primary CFT of fallopian tube was made. To our knowledge, this is the first report of CFT occurring in female reproductive tract. Awareness of CFT and its distinctive features is important to avoid a diagnostic pitfall caused by histologic similarities to other spindle cell or calcifying lesions in unusual locations. Although marginal excision is usually adequate for most of CFT, long-term follow-up is suggested as delayed recurrence might occur infrequently.

High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer.

Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real-time RT-PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real-time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP-high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP-high gastric cancer showed significantly worse survival compared with that of CIMP-low/CIMP-negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP-high was an independent prognostic factor.

Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer.

BACKGROUND AND OBJECTIVES: This study was conducted to investigate whether and how macrophages recruited to tumor microenvironments (tumor-associated macrophages, TAMs) were involved in angiogenesis and lymphangiogenesis of gastric cancer (GC). METHODS: TAMs, microvessel density (MVD), and lymphatic vessel density (LVD) in 115 cases of GC tissue were assessed by immunohistochemistry (IHC) staining of CD68, CD34, and D2-40, respectively. Preoperative blood samples from 43 patients were obtained to detect serum levels of vascular endothelial growth factor (VEGF) and VEGF-C. A co-culture system was also developed to study effects and underlying mechanisms of THP-1 macrophages on SGC7901 GC cells. RESULTS: TAMs numbers were closely related to serosa invasion, lymph node metastasis and tumor, nodes, and metastases stage and a positive correlation existed between the TAMs count and MVD and LVD. Additionally, TAMs were associated with preoperative serum levels of VEGF and VEGF-C, the expression of VEGF and VEGF-C protein in macrophages was up-regulated in the co-culture system, and inhibition of the NF-κB pathway in macrophages induced a significant reduction in the expression of VEGF and VEGF-C in both macrophages and GC cells (all P<0.05). CONCLUSIONS: TAMs may promote angiogenesis and lymphangiogenesis of GC, possibly by enhancing VEGF and VEGF-C expression.

[High-dose tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the clinical outcomes of high-dose tirofiban in patients with ST-elevation myocardial infarction (ASTEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 104 consecutive ASTEMI patients undergoing primary PCI were enrolled from January 2010 to February 2011. They were randomized into the high-dose tirofiban group (n = 52) and the normal-dose tirofiban group (n = 52). We measured the sumST-segment resolution of ECG post-PCI respectively and left ventricular ejective fraction (LVEF) at Day 90 post-PCI. RESULTS: After PCI, the sumST-segment resolution of ECG of the high-dose tirofiban group significantly improved than that of the normal-dose tirofiban group (38% ± 12% vs 34% ± 13%, P < 0.05). Before PCI, LVEF of two groups is 50.2% ± 1.4% vs 49.6% ± 1.1% (P > 0.05), but at day 90 post-PCI, LVEF had significant difference between two groups (60.1% ± 1.1% vs 56.0% ± 1.2%, P < 0.05). The rates of major and moderate hemorrhage did not differ significantly between two groups. CONCLUSION: High-dose tirofiban improves myocardial reperfusion and clinical outcome. It re-emphasizes the importance of further platelet aggregation inhibition in ASTEMI patients undergoing primary PCI.

[High maintenance dose of clopidogrel improves long-term clinical outcomes in patients with elective percutaneous coronary intervention].

OBJECTIVE: To evaluate the efficacy of a 300 mg loading dose of clopidogrel followed by 150 mg as maintenance dose in patients with percutaneous coronary intervention (PCI). METHODS: A total of 108 consecutive patients undergoing elective PCI were recruited from our hospital from July 2007 to July 2008. A 300 mg loading dose was administered prior to PCI. Then they were randomized to receive clopidogrel 75 mg (n = 55) or 150 mg (n = 46) daily for 30 days. From Day 30 to Month 6 post-operation, all of them received 75 mg/d clopidogrel and were followed up for a mean period of 6 months. RESULTS: Thirty days after PCI, the platelet inhibition of the 150 mg group was significantly higher than the 75 mg group (64.2% ± 13.3% vs 52.6% ± 14.3%, P = 0.00). The ratios of fatal or non-fatal myocardial infarction (MI) (1(1.8%) vs 3 (6.5%), P = 0.405) and target vessel revascularization (TVR) (4(7.2%) vs 6 (13.0%), P = 0.714) were significantly lower in the 150 mg group than those in the 75 mg group. So the overall incidence of MACE including death, MI and TVR was obviously lower in the 150 mg group than that in the 75 mg group (13.0% vs 20.2%, absolute risk reduction 7.3%). CONCLUSION: A high clopidogrel maintenance dose of 150 mg daily for the first month after PCI reduces the risk of long-term adverse events in patients with elective percutaneous coronary intervention.

[Prognostic significance of admission N-terminal pro-brain natriuretic peptide in predicting angiographic no-reflow phenomenon during percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To determine the relationship between N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and angiographic no-reflow phenomenon in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI). METHODS: The data of 106 consecutive AMI patients undergoing primary PCl were collected and analyzed retrospectively. NT-proBNP was obtained pre-PCI at admission. According to the NT-proBNP level, they were divided into normal and elevated NT-proBNP groups. The no-reflow phenomenon was defined as an angiographic outcome of Thrombolysis In Myocardial Infarction (TIMI) grade < 3 without accompanying mechanical factors. RESULTS: The patients with elevated NT-proBNP on admission had a higher incidence of no-reflow phenomenon than those with NT-proBNP level. Compared to normal reflow counterparts, no-reflow patients had a higher NT-proBNP level [1883 ng/L (484 ∼ 5500 ng/L) vs 220 ng/L (87 ∼ 926 ng/L) P = 0.046]. Multivariate analysis showed that a high NT-proBNP level (NT-proBNP > 1765 ng/L) on admission was an independent predictor of no-reflow. This cut-off value yielded a sensitivity of 60.0% and a specificity of 87.5% respectively. CONCLUSION: The NT-proBNP level on admission may be a prognostic biomarker in the prediction of the development of angiographic "no-reflow" phenomenon after primary PCI for AMI patients.

Preparation of rigid polyurethane foam from lignopolyol obtained through mild oxypropylation.

Lignin, one of the main components of lignocellulose, can be used as an alternative to chemical polyols in the production of polyurethane because of its abundant phenolic and alcohol hydroxyls. Traditionally, lignin is directly applied in the preparation of polyurethane; however, modified lignin has been proved to be superior, especially that obtained by the oxypropylation reaction. Therefore, lignopolyol obtained by mild and efficient oxypropylation was utilized in the production of rigid polyurethane foam in this study. Specifically, the effects of the content of lignopolyol on the chemical structure, morphological structure, mechanical properties and thermal stability of the lignin-based rigid polyurethane foam were investigated. It was found that the compressive strength of the rigid polyurethane foam was significantly improved with the addition of lignopolyol compared with that of the pure polyurethane foam, which was attributed to the fact that oxypropylation made lignin into highly branched and functionalized polyols by transforming all phenolic hydroxyls into aliphatic hydroxyls. Moreover, when the molal weight of lignopolyol accounted for 40% of the added polyols, the generated foam showed optimal uniformity and regularity, and the compressive strength reached 0.18 MPa, meeting the requirements of industrial application, below which, the amount of undesired reactions is bound to increase. As a consequence, the added amount of lignopolyol was increased as much as possible on the basis of guaranteeing the desired properties, which was more conducive to realizing the green degradation and economic synthesis of rigid polyurethane foam.

[Clinical observation on acupuncture for symptom burden in gastric cancer patients undergoing adjuvant chemotherapy after gastrectomy].

OBJECTIVE: To observe the efficacy of acupuncture on symptom burden in patients with gastric cancer during adjuvant chemotherapy after gastrectomy. METHODS: A total of 58 patients were randomized into a high-dose acupuncture group (19 cases, 5 cases dropped off), a low-dose acupuncture group (20 cases, 6 cases dropped off) and a control group (19 cases, 2 cases dropped off). Conventional chemotherapy and antiemetic treatment were adopted in the control group. On the basis of the treatment in the control group, acupuncture was applied 7 times each chemotherapy cycle for totally 21 times in the high-dose acupuncture group, and 3 times each chemotherapy cycle for totally 9 times in the low-dose acupuncture group. Baihui (GV 20), Zusanli (ST 36), Neiguan (PC 6), etc. were selected in the two acupuncture groups, as well as back-shu points selected by the meridian heat sensing technique. Electroacupuncture was connected to ipsilateral Zusanli (ST 36) and Neiguan (PC 6), with continuous wave, 2 Hz in frequency for 20 min. The Edmonton symptom assessment system (ESAS) score was observed on day 1-7, 14, and 21 of each cycle of chemotherapy respectively in the 3 groups. RESULTS: The symptom burden was worst within 7 days of each cycle of chemotherapy in the 3 groups. After the 3rd chemotherapy cycle, the total score of ESAS in the low-dose acupuncture group was lower than the control group (P<0.05), the total score and the scores of feeling of non-well being, pain and shortness of breath of ESAS in the acupuncture group (the high-dose acupuncture group combined with the low-dose acupuncture group) were lower than the control group (P<0.05). CONCLUSION: Acupuncture shows promising effect in controlling symptom burden during adjuvant chemotherapy in gastric cancer patients after gastrectomy.

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

[Comparison of clinical outcomes between laparoscopic-assisted and hand-assisted laparoscopic operations in colorectal cancer].

OBJECTIVE: To compare the clinical outcomes of laparoscopic-assisted versus hand-assisted laparoscopic radical operations in colorectal cancer and evaluate the safety and indications of hand-assisted laparoscopic operations. METHODS: A total of 64 consecutive colorectal cancer patients enrolled from November 2009 to December 2011 at our hospital were randomly and prospectively divided into 2 groups: hand-assisted laparoscopic operation (HALS) (n = 32) and laparoscopic-assisted operation (n = 32). And such clinicopathologic features as safety, operative curability and postoperative recovery were compared between two groups. RESULTS: Neither death nor conversion-to-open-surgery was reported among all patients. There were no statistical differences in such clinicopathologic features as age, gender, body mass index, mass size and location (all P > 0.05). There were statistically a shorter operation time [(127 ± 31) min vs (184 ± 71) min, P = 0.022] and a smaller number of Trocar (2.4 vs 5.0, P = 0.015) in the HALS group. However, the laparoscopic-assisted group had a lesser volume of blood loss [(82 ± 31) ml vs (150 ± 42) ml, P = 0.008] and a smaller postoperative 48 h drainage flow [(170 ± 52) ml vs (208 ± 58) ml, P = 0.020]. Moreover, no statistical differences existed in the length of bowel resection [(19 ± 5) cm vs (18 ± 4) cm], amount of lymph nodes dissection (16 ± 4 vs 16 ± 3), postoperative complications [12.5% (4/32) vs 25.0% (8/32)], time of intestinal function recovery [(1.7 ± 0.9) d vs (1.8 ± 0.7) d], time of semifluid tolerance [(2.9 ± 1.3) vs (2.8 ± 1.2) d], hospitalization expenses [(4.8 ± 0.6) 10 000 yuan vs (4.9 ± 0.4) 10 000 yuan] and postoperative hospital stay [(6.7 ± 2.3) d vs (6.6 ± 2.3) d] (all P > 0.05). CONCLUSION: HALS is both safe and efficacious for colorectal cancer patients.

[Reconstruction of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy: a meta-analysis of prospectively controlled trials].

OBJECTIVE: To compare the reconstructing safety of pancreaticogastrostomy (PG) versus pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). METHODS: The articles of prospectively controlled trials published until late December 2010 comparing PJ and PG after PD were searched by the means of MEDLINE, EMBASE, Cochrane Controlled Trials Register databases and Chinese Biomedical Database. After quality assessment of all included prospective controlled trials, a meta-analysis was performed with Review Manager 5.0 for statistic analysis. RESULTS: A total of 6 prospective controlled trials were included. Among 867 patients analyzed, 440 underwent PG and 426 PJ. A meta-analysis of 6 prospective controlled trials (including randomized control trial (RCT) and non-randomized prospective trial) revealed significant differences between PJ and PG regarding the overall postoperative complication rates [OR 0.53, 95%CI (0.30, 0.95), P = 0.03], pancreatic fistula [OR 0.47, 95%CI (0.22, 0.97), P = 0.04] and intra-abdominal fluid collection [OR 0.42, 95%CI (0.25, 0.72), P = 0.001]. The differences in biliary fistula, intra-abdominal (IAC) complications and mortality were of no significance. Meta-analysis of 4 RCTs revealed significant differences between PJ and PG regarding intra-abdominal fluid collection [OR 0.46, 95%CI (0.26, 0.79), P = 0.005]. The differences in pancreatic fistula, overall postoperative complications, biliary fistula, intra-abdominal complications and mortality were of no statistical significance. CONCLUSION: Through a meta-analysis of 6 prospective controlled trials, there are significant differences between PJ and PG regarding overall postoperative complications, pancreatic fistula and intra-abdominal fluid collection. Significant differences exist between PJ and PG regarding intra-abdominal fluid collection. The safety profiles of PG and PJ are comparable.

Pitavastatin Combined with Ezetimibe Treatment was an Effective Approach to Non-IRA Lesion of ST-segment Elevation Myocardial Infarction Patients with Primary Percutaneous Coronary Intervention.

OBJECTIVE: ST-Segment Elevation Myocardial Infarction (STEMI) patients with the multivessel disease have distinctive plaque characteristics in non-IRA lesions. Intensive statin therapy was a potential approach to treat STEMI patients with the non-IRA disease. However, there is still poor evidence about the therapeutic effect. In this study, we have evaluated the detailed therapeutic effect of statin plus ezetimibe intensive therapy. METHODS: For STEMI patients with non-IRA disease undergoing primary Percutaneous Coronary Intervention (PCI), 183 control STEMI patients without non-IRA disease undergoing primary PCI, and 200 STEMI patients with non-IRA disease undergoing primary PCI were introduced into this study. 200 STEMI patients with non-IRA disease undergoing primary PCI were divided into Normal group, Intensive group, Normal & Combined group, and Intensive & Combined group. The baseline information for each participant was recorded. Meanwhile, the physiological and biochemical indicators of each member with different treatments were collected after one-year follow-up. RESULTS: For STEMI patients with non-IRA disease undergoing primary PCI, no differences could be detected in multiple indexes such as OCT examination results, age, stroke, etc. However, diabetes mellitus, smoking, and coronary Gensini score were different between different groups (P<0.05). After one year follow-up, cholesterol, low-density lipoprotein, coronary Gensini score, thin-cap fibroatheroma, length of non-infarcted arterial lesions, non-infarct artery lesion range, myocardial infarction again, and revascularization again were significantly different between different groups (P<0.05). CONCLUSION: The results mentioned above suggested that pitavastatin combined with ezetimibe was an effective approach for STEMI patients with non-IRA disease undergoing primary PCI. The results obtained in this study have provided a novel method for the treatment of STEMI patients with non-IRA disease undergoing primary PCI.

Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway.

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1ß (IL-1ß) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-ß and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.

High expression of PRL-3 can promote growth of gastric cancer and exhibits a poor prognostic impact on patients.

High expression of PRL-3 had been implicated in lymph node metastasis of gastric cancer. In the present study, we detected the expression of PRL-3 in primary gastric cancer tissue, and evaluated its role in gastric cancer growth and the prognostic impact on patients. PRL-3 phosphatase expression was measured in 137 gastric tumor samples by using the immunohistochemistry method, and the overall survival rate was compared between the patients with high PRL-3 expression (n = 85) and those with moderate or low PRL-3 expression (n = 52). RNA interference, mediated by recombinant lentivirus expressing artificial PRL-3 miRNA, was used to knockdown PRL-3 expression in SGC7901 cell line. MTT assay and animal experiment were conducted to determine the role of PRL-3 in the proliferation of SGC7901 cells and tumor growth. PRL-3 expression was more frequently detected in tumors with a diameter >40 mm and in advanced stages. Furthermore, the overall survival rate of high PRL-3 expression was significantly lower than that of moderate or low PRL-3 expression (P < 0.001), and multivariate analysis showed that PRL-3 expression level independently influences the survival of patients (P = 0.024). Importantly, knockdown of PRL-3 significantly suppressed the proliferation of SGC7901 cells and slowed the tumor growth compared with controls (P < 0.05). PRL-3 is associated with gastric cancer progression. High PRL-3 expression in the primary lesion had a negative impact on prognosis. PRL-3 plays a key role in the control of gastric cancer growth. PRL-3 should be considered as a potential therapeutic target and a prognostic factor.

[Value of spiral CT plus endoscopic ultrasonography (EUS) and spiral CT plus PET-CT in the preoperative assessment of gastric cancer invasion to the pancreas].

OBJECTIVE: To evaluate the value of EUS and PET-CT in combination with spiral CT in preoperative assessment of gastric cancer invasion to the pancreas. METHODS: Sixty advanced gastric cancer patients with suspected pancreatic invasion detected by spiral CT were selected in this study. All the 60 cases were then examined by EUS and 14 of them by PET-CT. The results were compared and evaluated with the findings during surgical operation and pathological results. RESULTS: The rate of correct preoperative diagnosis of pancreatic invasion by spiral CT in advanced gastric cancer patients was 63.3%, with an overdiagnosis rate of 36.7%. The diagnostic accuracy was increased to 87.8% and overdiagnosis reduced to 7.3%, when combined with EUS. There was a significant difference in diagnostic accuracy between spiral CT alone and spiral CT combined with EUS (P<0.01), but no significant difference between spiral CT alone and spiral CT combined with PET-CT (P>0.05). Spiral CT-EUS was more valuable in assessment of tumor location and invasion than PET-CT (P<0.01). CONCLUSION: The accuracy of spiral CT alone in the preoperative assessment of advanced gastric cancer with invasion to the pancreas is not high enough yet at present. Spiral CT combined with EUS can provide more accurate information on the tumor location, invasion site and extent of gastric cancer invasion to the pancreas, and reduce the overstaging rate caused by spiral CT alone. However, spiral CT combined with PET-CT does not show such improvement significantly.

[Clinical outcomes of trimetazidine in patients with acute ST segment elevation myocardial infarction without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To evaluate prospectively the clinical outcomes of trimetazidine (TMZ) in patients with acute ST segment elevation myocardial infarction (STEMI) without ST segment resolution (STR) after primary percutaneous coronary intervention (PPCI). METHODS: From August 2005 to October 2007, 138 acute STEMI patients without STR after PPCI were randomly assigned to either with TMZ therapy (TMZ group, n = 70) or without TMZ (control group, n = 68). Baseline characteristics, PCI features and clinical outcomes during hospitalization were compared between the two groups. Left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at Days 30 and 180 after discharge were also compared. RESULTS: The baseline clinical characteristics were comparable between the two groups. There was no significant difference in MACE rates at Days 30 and 180 between the two groups (10/70 vs 11/68, P > 0.05; 15/70 vs 13/68, P > 0.05, respectively). The LVEFs of TMZ group at Days 30 and 180 were significantly superior to the control group (51 +/- 8)% vs (45 +/- 7)%, P < 0.05; (56 +/- 7)% vs (49 +/- 8)%, P < 0.05, respectively). CONCLUSION: Use of TMZ for patients with acute STEMI without STR after primary PCI can improve the left ventricular function at Days 30 and 180.

[Associations of E-cadherin gene (CDH1) and hereditary gastric cancer in China].

OBJECTIVE: To investigate the protein expression, methylation promoter, somatic and germ-line mutations of E-cadherin gene (CDH1) in hereditary gastric cancer in China and to investigate its possible roles. METHODS: Eight probands diagnosed with ICG-HGC criterion were enrolled in our database from June 1994 to October 2007. Tumor tissues were detected for CDH1 expression by using immunohistochemistry (IHC) methods. CDH1 DNA sequencing was performed for all its 16 exons both in tumor and normal tissues of the same patients to detect somatic and germ-line mutations. Methylation promoter study was performed by using specific primers and polymerase chain reaction (PCR) methods. RESULTS: IHC analysis confirmed that the CDH1 expression was negative in 7 probands and downregulated in the other on proband. Six mutations in five probands were found with DNA sequencing: two silent mutations and four missense mutations. All six mutations were absent in normal tissues, thereby excluded its presence in germ-line cells. Both DNA missense mutations and gene silencing through promoter methylation was found in 4 probands. Two probands has only promoter methylation and one proband had only silent mutation. No DNA missense mutations or promoter methylation was found in one proband. CONCLUSIONS: CDH1 gene germ-line mutations are relatively rare in hereditary gastric cancer in China, and whereas CDH1 somatic mutations and promoter methylation synergistically induce CDH1 downregulation in these patients.