A nomogram for predicting overall survival in patients with type II endometrial carcinoma: a retrospective analysis and multicenter validation study.

OBJECTIVE: Type II endometrial cancer (EC) is associated with high risk of metastasis and poor prognosis. We aimed to develop a nomogram for predicting survival probability in patients with type II EC. PATIENTS AND METHODS: Data from a total of 4,117 patients with confirmed type II EC were pulled from the Surveillance, Epidemiology, and End Results (SEER) database, and were randomly divided into a training set and an internal verification set. A nomogram was constructed based on the training set. The concordance index (C-index), area under the ROC curve, and calibration plots were used to evaluate the identification and calibration of the nomogram. The SEER internal validation set and the Chinese multicenter data set (74 patients) were used to verify discriminations and corrections of the model. RESULTS: Multivariate analysis indicated that age, marital status, tumor size, T stage, N stage, M stage, surgery, radiotherapy, and chemotherapy were independent factors affecting the prognosis of type II EC patients (p<0.001). The corresponding nomogram has showed excellent calibration and discrimination (C-index [95% CI], 0.752 [0.738-0.766]). The model was verified in the internal verification set (0.760 [0.739-0.781]) and the Chinese multicenter set (0.784 [0.607-0.961]). In addition, the AUC further confirmed the accuracy of the nomogram in predicting survival. The calibration curve of OS within 5 years confirmed good calibration of the nomogram. CONCLUSIONS: This model and the corresponding risk classification system may provide useful tools for clinicians to evaluate the long-term prognosis of patients and carry out personalized clinical evaluation.

[Risk factors for multiple debridements of the patients with deep incisional surgical site infection after spinal surgery].

OBJECTIVE: To investigate the risk factors that contribute to multiple debridements in patients suffering from deep incisional surgical site infection after spinal surgery and advise medical personnel to pay special attention to these risk factors. METHODS: We retrospectively enrolled 84 patients who got deep incisional surgical site infection after spinal surgery from Jan. 2012 to Dec. 2017. The infections occurred within 30 days after the surgery, and the identification met the criteria of deep incisional surgical site infection of Centers of Disease Control (CDC). Early debridement with first stage closure of the wound and a continuous inflow-outflow irrigation system was used, and reasonable antibiotics were chosen according to the bacterial culture results. During the treatment, the vital signs, clinical manifestations, blood test results, drainage fluid colour and bacterial culture results were acquired. If the infection failed to be controlled or relapsed, a second debridement was performed. Of the 84 cases, 60 undergwent single debridement which included 36 male cases and 24 female cases, and the age ranged from 36 to 77 years, with a mean of 57.2 years. Twenty four had multiple debridements (twice in 14 cases, three times in 6 cases, four times in 1 case, five times in 2 cases, six times in 1 cases) which included 17 male cases and 7 female cases, and the age ranged from 21 to 70 years, with a mean of 49.5 years. Risk factors that predispose patients to multiple debridements were identified using univariate analysis. Risk factors with P values less than 0.05 in univariate analysis were included together in a multivariate Logistic regression model using back-forward method. RESULTS: Multiple debridements were performed in 28.6% of all cases. The hospital stay of multiple debridements group was (82.4±46.3) days compared with (40.4±31.5) days in single debridement group (P=0.018). Instrumentation was removed in 6 cases in multiple debridements group and 4 cases in single debridement group (P=0.049). Flap transplantation was performed in 7 cased in multiple debridements group while none in single debridement group (P < 0.001). Diabetes, primary operation duration longer than 3 hours, primary operation blood loss more than 400 mL, bacteriology examination results, distant site infection were significantly different between the two groups in univariate analysis. In multivariate analysis, primary operation duration longer than 3 hours (OR=3.60, 95%CI: 1.12-11.62), diabetes (OR=3.74, 95%CI: 1.06-13.22), methicillin-resistant Staphylococcus aureus (MRSA) infected (OR=16.87, 95%CI: 2.59-109.73) were the most important risk factors related to multiple debridements in the patients with deep incisional surgical site infection after spinal surgery. CONCLUSION: Diabetes, primary operation duration more than 3 hours, MRSA infected are independent risk factors for multiple debridements in patients suffering from deep incisional surgical site infection after spinal surgery. Special caution and prophylaxis interventions are suggested for these factors.

Correlation of SOCS3 gene polymorphism with childhood asthma.

OBJECTIVE: To explore the correlation of the suppressor of cytokine signaling 3 (SOCS3) gene polymorphism with childhood asthma. PATIENTS AND METHODS: A total of 204 asthma children (observation group) and 235 healthy children (control group) were enrolled. General clinical information of enrolled subjects was collected. Inflammatory factors and pulmonary function test indexes in each subject were examined. Moreover, the polymorphism of SOCS3 gene rs9914220 was detected with the TaqMan-MGB probe. RESULTS: Asthma children in the observation group exhibited higher levels of interleukin-4 (IL-4), IL-17, and IL-33 than those of the control group (p<0.05). The forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (%), peak expiratory flow (PEF), and FVC in the observation group were lower than those in the control group. However, the residual volume (RV), and RV/total lung capacity (TLC) ratio were higher in observation group than those in control group (p<0.05). Distribution frequency of the genotypes varied a lot between the two groups (p<0.05). However, we did not observe a significant difference in SOCS3 alleles between the two groups (p>0.05). According to the analysis of the genetic model, there were differences in dominant and cumulative models between the two groups (p<0.05), whereas the recessive model was not different between the two groups (p>0.05). CONCLUSIONS: Levels of inflammatory factors and pulmonary functions help to effectively monitor the progression of childhood asthma, thus increasing the clinical diagnosis rate. The polymorphism of the SOCS3 gene rs9914220 site is correlated with the onset of childhood asthma.

[Efficacy analysis of Smith-Petersen osteotomy assisted by releasing disk space from posterior approach for thoracolumbar kyphosis].

Objective: To evaluate the efficacy and safety of Smith-Petersen osteotomy (SPO) assisted by releasing disk space from posterior approach for thoracolumbar kyphosis. Methods: A review was conducted on 8 patients (3 males and 5 females) with thoracolumbar kyphosis were treated with SPO assisted by releasing disk space from posterior approach at Department of Orthopaedics, Peking University Third Hospital from June 2016 to September 2017. The age was 56.5 years (range:18-71 years). There were 3 cases of Scheuermanns kyphosis, 2 cases of degenerative kyphosis, 1 case of proximal junctional kyphosis (PJK) after lumbar surgery, and 2 cases of kyphosis after thoracolumbar laminectomy. The paired t test was used for statistical analysis in thoracolumbar kyphosis angle, osteotomy segment kyphosis angle, sagittal vertical value (SVA), visual analogue score (VAS), Oswestry dysfunction index (ODI) before and after surgery. Statistical difference was confirmed with P<0.05. Results: Osteotomy level included 2 cases in T(11-12), 3 cases in T(12)-L(1), 3 cases in L(1-2.) The average operation time was 339 min (range: 247-416 min), bleeding volume was 1 275 ml (range: 500-2 500 ml). The mean follow-up time was 16.5 months (range: 12-24 months). The average thoracolumbar kyphosis angle was 59.9° (range: 40°-73°) pre-operation, 9.5°(range:-5.1°-20°) post-operation and 13.5°(range:-1.3°-28°) at the latest follow-up. It made an average correction with 46.4°and corrective rate with 78.0%. The osteotomy segment kyphosis angle was 37.9° (range: 26°-46°) pre-operation, -1.3° (range:-11°-13°) post-operation making an 39.2° open-up angle, and 2.0° (range:-13.5°-13°) at the latest follow-up. Lumbar lordosis was 47.5° (range: 2°-76°) pre-operation, 41.2°(range:15°-62°) post-operation and 36.9°(range:15°-58°) at the latest follow-up. SVA was 54 mm(range:-34 mm-149 mm) pre-operation and 39 mm(range:-3 mm-119 mm) at the latest follow-up. VAS score of low back pain was 6.3(range:0-9) pre-operation and 3.0(range:0-6) at the latest follow-up. ODI score was 21.9(range: 0-42) pre-operation and 11.0(range: 0-26) at latest follow-up. Comparing to pre-operation value, there were statistical difference in the thoracolumbar kyphosis angle(t= 8.547, P=0.000), osteotomy segment kyphosis angle(t=9.739, P=0.000), VAS(t=3.077, P=0.018), ODI(t=5.800, P=0.001) at the latest follow-up. There was no neuropathic complication in all patients. Cerebrospinal fluid leakage occurred in 2 cases with spinal surgery history, and recovered after symptomatic treatment. Conclusions: SPO assisted by releasing disk space from posterior approach could safely achieve effective correction of rigid thoracolumbar kyphosis deformity within 40°.

[A clinical study of the association between hepatic controlled attenuation parameter and metabolic syndrome].

Objective: To investigate the association between hepatic controlled attenuation parameter (CAP) and metabolic syndrome (MetS) and the correlation of CAP and its changes with the incidence of MetS. Methods: A total of 2461 subjects who underwent physical examination from July 2013 to September 2015 were enrolled. Spearman correlation analysis was used to investigate the correlation of CAP with the number of MetS components and each MetS component, and the chi-square test was used to investigate the prevalence rates of MetS and each component under different CAP levels. Logistic regression analysis was used to analyze the odds ratio (95% confidence interval (CI)) of MetS under different CAP levels. A total of 230 subjects without baseline MetS were selected; in a prospective cohort study, these subjects were divided into groups according to the baseline CAP, change in CAP, and percent change in CAP, and the chi-square test was performed to compare the incidence of MetS. The Cox regression analysis was used to analyze the values of baseline CAP, change in CAP, and percent change in CAP in predicting MetS. Results: CAP was positively correlated with the number of MetS components (r = 0.309, P < 0.01) and significantly correlated with all components. There were significant differences in the prevalence rates of MetS and its components under different CAP levels (< 238 dB/m, 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m) (P < 0.05). After the adjustment for sex and age, with < 238 dB/m as a reference, the odds ratios (95% CI) of MetS in patients with CAP levels of 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m were 1.784 (1.369-2.325), 2.936 (2.292-3.760), and 4.363 (3.435-5.543), respectively (all P < 0.05). Follow-up data showed that 28 patients (12.2%) developed MetS. After the adjustment for related factors, the hazard ratios (95% CI) of MetS in patients with baseline CAP > 238 dB/m, change in CAP > 30 dB/m, and percent change in CAP > 25.0% were 3.337 (1.163-9.569), 7.732 (2.453-24.366), and 11.656 (3.329-40.813), respectively (all P < 0.05). Conclusion: CAP is closely associated with MetS and its components. CAP and its change can be used to predict the risk of MetS.

Intraosseous Injection of Simvastatin in Poloxamer 407 Hydrogel Improves Pedicle-Screw Fixation in Ovariectomized Minipigs.

BACKGROUND: Osteoporosis leads to poor osseointegration and reduces implant stability. Statins have been found to stimulate bone formation, but the bioavailability from oral administration is low. Local application may be more effective at augmenting bone formation and enhancing implant stability. This study was performed to evaluate the efficacy of an intraosseous injection of simvastatin in thermosensitive poloxamer 407 hydrogel to enhance pedicle-screw fixation in calcium-restricted ovariectomized minipigs. METHODS: Nine mature female Guangxi Bama minipigs underwent bilateral ovariectomy and were fed a calcium-restricted diet for 18 months. Simvastatin (0, 0.5, or 1 mg) in thermosensitive poloxamer 407 hydrogel was injected into the lumbar vertebrae (L4-L6), and titanium alloy pedicle screws were implanted. Bone mineral density (BMD) measurements of the lumbar vertebrae were determined by dual x-ray absorptiometry (DXA) before and 3 months after treatment. The lumbar vertebrae were harvested and analyzed with use of microcomputed tomography, biomechanical pull-out testing, histological analysis, and Western blot analysis for bone morphogenetic protein (BMP)-2 and vascular endothelial growth factor (VEGF) expression. RESULTS: Evaluation over a 3-month study period demonstrated that the BMD of the vertebrae injected with 0.5 and 1.0 mg of simvastatin had increased by 31.25% and 31.09%, respectively, compared with vehicle-only injection (p ≤ 0.00014 for both) and increased by 32.12% and 28.16%, respectively, compared with the pre-treatment levels (p < 0.0001 for both). A single injection of simvastatin in poloxamer 407 increased trabecular volume fraction, thickness, and number and decreased trabecular separation (p ≤ 0.002). The bone formation and mineral apposition rates significantly increased (p ≤ 0.023). The percentage of osseointegration in the simvastatin 0.5 and 1-mg groups was 46.54% and 42.63% greater, respectively, than that in the vehicle-only group (p ≤ 0.006), and the maximum pull-out strength was 45.75% and 51.53% greater, respectively, than in the vehicle-only group (p ≤ 0.0005). BMP-2 and VEGF expressions were higher than for the vehicle-only injection. CONCLUSIONS: A single intraosseous injection of simvastatin in thermosensitive poloxamer 407 hydrogel stimulated bone formation, increased BMD, improved bone microstructure, promoted osseointegration, and significantly enhanced the stability of pedicle screws in calcium-restricted ovariectomized minipigs. CLINICAL RELEVANCE: These results provide rationale for evaluating intraosseous injection of simvastatin in poloxamer 407 to enhance implant fixation in patients with osteoporosis.

[The clinical analysis of instrumentation failure after corrective surgery for thoracolumbar focal kyphosis].

OBJECTIVE: To analyze the etiology of instrumentation failure after corrective surgery for thoracolumbar focal kyphosis, and make suggestion for treatment. METHODS: Retrospective study for 8 patients with thoracolumbar focal kyphosis who underwent surgical treatment and suffered instrumentation failure from June 2005 to December 2011 was made. The surgical procedures included pedicle subtraction osteotomy (PSO), anterior opening-posterior closing osteotomy and correction (AOPC), and posterior vertebral column resection (VCR). The reasons of instrumentation failure were analyzed and revision surgeries were performed. RESULTS: The incidence of instrumentation failure was 6.3%. The average occurrence time was 22.5 months after surgery. Except one had failure in 3 months after surgery, all cases happened after 1 year. In this series, there were 5 cases with post-tuberculosis, 2 cases with post-traumatic kyphosis and 1 case with congenital kyphosis. For the surgical procedure, 7 cases underwent VCR and 1 case AOPC. After the instrumentation failure, all cases had back pain, and 3 of them had combined neurological symptoms. The reasons or risk factors of instrumentation failure included non-fusion of bone graft, VCR procedure, sink of the titanium mesh, insufficiency of anchor sites, and more severe kyphosis. All the 8 cases were treated with revision surgery and got good results. CONCLUSIONS: The instrumentation failure of thoracolumbar focal kyphosis is relatively late occurred, and can develop with various reasons. Positive revision surgery is suggested for the instrumentation failure, and good results can be expected.

[Clinical analysis of 67 cases of surgical site infection after spine surgery].

OBJECTIVE: To investigate the treatment of surgical site infection(SSI) after spine surgery. METHODS: Sixty-seven patients (aged 20-77 years with mean age of 51 years) with etiologically-confirmed surgical site infection after spine surgery in Peking University Third Hospital between July 2004 and December 2012 were retrospectively analyzed. There were 39 male and 28 female patients; 47 lumbar infections, 4 thoracic infections, 7 lower cervical infections and 8 upper cervical infections; 64 early infections and 3 delayed infections; 23 superficial infections and 44 deep infections; 47 monomicrobial infections and 20 polymicrobial infections. Ninety-six strains of bacteria were identified from the bacterial culture of 67 patients. Sixty strains were gram-positive pathogenic bacteria (62.5%), and the top three species were Staphylococcus aureus, S. epidermidis and Enterococcus faecalis. The remaining 36 strains were gram-negative pathogenic bacteria (37.5%), and the 3 species most predominant were Escherichia coli, Enterobacter cloacae, and Acinetobacter baumannii. All the patients with SSI were administered antibiotics. Debridement and irrigation-suction was performed if little symptomatic improvement was achieved in two-to-three days of antibiotics treatment, patients underwent 1-5 times of debridements (mean 1.5 times). RESULTS: One patient was dead of MRSA septicemia, whom manifested as high fever, alalia and incision swelling when the infection occurred. The patient underwent polymicrobial of pulmonary infection and urinary tract infection during the period of hospitalization, and finally died of multiple organ failure. Sixty-six cases had wound healed, and they were followed up for 25-117 months (average 70 months), no recurrence of infection was found at last follow-up. Among the 65 cases of internal fixation, 56 cases reserved the implants, while implants were removed in other 9 cases for controlling infection. CONCLUSION: Reasonable antibiotics and irrigation-suction are effective methods for managing surgical site infections after spine surgery and prevent removal of implants.

Construction of a protein-protein interaction network of Wilms' tumor and pathway prediction of molecular complexes.

Wilms' tumor (WT), or nephroblastoma, is the most common malignant renal cancer that affects the pediatric population. Great progress has been achieved in the treatment of WT, but it cannot be cured at present. Nonetheless, a protein-protein interaction network of WT should provide some new ideas and methods. The purpose of this study was to analyze the protein-protein interaction network of WT. We screened the confirmed disease-related genes using the Online Mendelian Inheritance in Man database, created a protein-protein interaction network based on biological function in the Cytoscape software, and detected molecular complexes and relevant pathways that may be included in the network. The results showed that the protein-protein interaction network of WT contains 654 nodes, 1544 edges, and 5 molecular complexes. Among them, complex 1 is predicted to be related to the Jak-STAT signaling pathway, regulation of hematopoiesis by cytokines, cytokine-cytokine receptor interaction, cytokine and inflammatory responses, and hematopoietic cell lineage pathways. Molecular complex 4 shows a correlation of WT with colorectal cancer and the ErbB signaling pathway. The proposed method can provide the bioinformatic foundation for further elucidation of the mechanisms of WT development.

Construction of polycythemia vera protein interaction network and prediction of related biological functions.

Here, polycythemia vera (PV)-related genes were screened by the Online Mendelian Inheritance in Man (OMIM), and literature pertaining to the identified genes was extracted and a protein-protein interaction network was constructed using various Cytoscape plugins. Various molecular complexes were detected using the Clustervize plugin and a gene ontology-enrichment analysis of the biological pathways, molecular functions, and cellular components of the selected molecular complexes were identified using the BiNGo plugin. Fifty-four PV-related genes were identified in OMIM. The protein-protein interaction network contains 5 molecular complexes with correlation integral values >4. These complexes regulated various biological processes (peptide tyrosinase acidification, cell metabolism, and macromolecular biosynthesis), molecular functions (kinase activity, receptor binding, and cytokine activity), and the cellular components were mainly concentrated in the nucleus, intracellular membrane-bounded organelles, and extracellular region. These complexes were associated with the JAK-STAT signal transduction pathway, neurotrophic factor signaling pathway, and Wnt signaling pathway, which were correlated with chronic myeloid leukemia and acute myeloid leukemia.

A single CT-guided percutaneous intraosseous injection of thermosensitive simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in ovariectomized minipigs.

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.

Construction of gene/protein interaction networks for primary myelofibrosis and KEGG pathway-enrichment analysis of molecular compounds.

The objective of this study was the development of a gene/protein interaction network for primary myelofibrosis based on gene expression, and the enrichment analysis of KEGG pathways underlying the molecular complexes in this network. To achieve this, genes involved in primary myelofibrosis were selected from the OMIM database. A gene/protein interaction network for primary myelofibrosis was obtained through Cytoscape with the literature mining performed using the Agilent Literature Search plugin. The molecular complexes in the network were detected by ClusterViz plugin and KEGG pathway enrichment of molecular complexes was performed using DAVID online. We found 75 genes associated with primary myelofibrosis in the OMIM database. The gene/protein interaction network of primary myelofibrosis contained 608 nodes, 2086 edges, and 4 molecular complexes with a correlation integral value greater than 4. Molecular complexes involved in KEGG pathways are related to cytokine regulation, immune function regulation, ECM-receptor interaction, focal adhesion, actin cytoskeleton regulation, cell adhesion molecules, and other biological behavior of tumors, which can provide a reliable direction for the treatment of primary myelofibrosis and the bioinformatic foundation for further understanding the molecular mechanisms of this disease.

Analysis of the gene-protein interaction network in glioma.

Glioma is the most aggressive type of brain tumor. Great progress has been achieved in glioma treatment, but the protein-protein interaction networks underlining glioma are poorly understood. We identified the protein-protein interaction network for glioma based on gene expression and predicted biological pathways underlying the molecular complexes in the network. Genes involved in glioma were selected from the Online Mendelian Inheritance in Man (OMIM) database. A literature search was performed using the Agilent Literature Search plugin, and Cytoscape was used to establish a protein-protein interaction network. The molecular complexes in the network were detected using the Clusterviz plugin, and pathway enrichment of molecular complexes was performed using DAVID online. There were 378 glioma genes in the OMIM database. The protein-protein interaction network in glioma contained 1814 nodes, 6471 edges, and 8 molecular complexes. There were 17 pathways (false discovery rate <1), which were related to cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, oocyte meiosis, progesterone-mediated oocyte maturation, transmembrane transport of small molecules, metabolism of amino acids, and notch signaling pathway, among others. Our results provide a bioinformatic foundation for further studies of the mechanisms of glioma.

PUMA gene transfection can enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells.

We explored whether p53 upregulated modulator of apoptosis (PUMA) gene transfection could enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells. The liposome-mediated recombinant eukaryotic expression vector PU-MA-pCDNA3 and empty vector plasmid were stably transfected into MCF-7 cells. Epirubicin (0.01-100 µM) was applied to MCF-7, MCF-7/PUMA, and MCF-7/pCDNA3 cells for 72 h. The MTT assay was used to calculate the cell survival rate in each group, and the 50% inhibitory concentration (IC50) was calculated. The IC50 values of epirubicin in MCF-7, MCF-7/PUMA, and MCF-7/pCDNA3 cells were 13 ± 1.4, 1.8 ± 0.2, and 10.7 ± 1.3 µM, respectively. The sensitivity of MCF-7/PUMA cells to epirubicin increased 7.2-fold. Epirubicin induced apoptosis in MCF-7 cells dose-dependently, but MCF-7/PUMA cell-induced apoptosis was more significant compared to controls. Low concentrations of epirubicin (0.1 µM) caused low levels of apoptosis of MCF-7/pCDNA3 (1.15 ± 0.26%) and MCF-7 cells (0.9 ± 0.24%), but significantly induced apoptosis of MCF-7/PUMA cells (6.44 ± 1.46%). High epirubicin concentration (1 µM) induced apoptosis in each group, but the epirubicin MCF-7/PUMA apoptosis rate (35.47 ± 9.36%) was significantly higher than that of MCF-7 (12.6 ± 3.73%) and MCF-7/ pCDNA3 (15.2 ± 5.17%) cells (P < 0 01). Flow cytometry and TUNEL assays for apoptosis detection showed similar results. PUMA protein expression in MCF-7/PUMA cells was significantly higher than that in MCF-7 and MCF-7/pCDNA3 cells by Western blot analysis. There-fore, stable transfection of PUMA can significantly enhance epirubicin-induced apoptosis sensitivity of MCF-7 breast cancer cells.

Effect of Rhizoma paridis total saponins on apoptosis of colorectal cancer cells and imbalance of the JAK/STAT3 molecular pathway induced by IL-6 suppression.

We observed the influence of different concentrations of Rhizoma paridis total saponins (RPTS) on the apoptosis of colorectal cancer cells and explored the internal mechanism involved. We determined whether RPTS influences the interleukin-6 (IL-6)/Janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) apoptosis molecular pathway and looked for colon cancer-related signal transduction pathways or targets inducing apoptosis. We also cultured SW480 colorectal cancer cells using different concentrations of RPTS (10, 20, 40, and 80 µg/ mL), and observed the effect of RPTS on SW480 cell morphology under a fluorescence inverted microscope. We detected serum IL-6 using the polymerase chain reaction and the expression of JAK-STAT3 protein by western blot. After treating SW480 with RPTS and Hoechst 33258 dyeing, we found that the typical apoptosis morphology had changed. Secretion of IL-6 in the serum decreased significantly (P < 0.05), and STAT3 levels were reduced. RPTS can significantly promote apoptosis in SW480 colorectal cancer cells. The mechanism may be that it suppresses the secretion of IL-6 and inhibits the IL-6/JAK-STAT3 protein signaling pathway.

[Mechanism of effect of intraventricular administration of histamine H1-receptor agonists on gastric acid secretion in rats].

The present experiment is undertaken to study the mechanism of the inhibitory effect of 2-pyridylethylamine (PEA, i.c.v.) on the gastric acid secretion. Gastric acid was continuously washed out with 37 degrees C saline by means of a perfusion pump in Wistar rats weighing 200-300 g. Drugs were injected into the third ventricle to examine the effect on pentagastrin-induced (160 micrograms/kg, s.c.) gastric acid secretion. The results were as follows: (1) Pretreatment with naloxone (2.5 micrograms, i.c.v.) blocked the inhibitory effect of PEA (10 micrograms, i.c.v.) on gastric acid secretion. (2) The inhibitory effect of PEA (5-20 micrograms, i.c.v.) was turned into an excitatory effect after subdiaphragmatic vagotomy in a dose-dependent manner, but not changed by bilateral adrenalectomy. (3) In vagotomized rats, pretreatment with CRF-antiserum (1:20,000, 2.5 microliters, i.c.v.) or bilateral adrenalectomy abolished the excitatory effect of PEA (10 micrograms, i.c.v.). (4) PEA (10 micrograms, i.c.v.) did not change the basal gastric acid secretion in vagotomized rats. These results suggest that histamine H1-receptor in brain may be involved in both the inhibitory and excitatory regulation of gastric acid secretion mediated by vagus nerve and the hypothalamus-pituitary-adrenal axis.