[Two new benzyl-benzoate glucosides from Plumeria rubra].

The components with hypoglycemic activity in Plumeria rubra were isolated and purified by various column chromatography techniques and activity tracing methods. The physical and chemical properties of all the purified monomer compounds were characterized and analyzed, and a total of six compounds were isolated and identified, including 6″-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(1), 6-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(2), 2-hydroxy-6-methoxy-benzyl-benzoate-2-O-ß-D-glucoside(3), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(4), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(5), and 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-xyloside(6). Compounds 1 and 2 were new compounds, and compounds 3-6 were isolated from Plumeria for the first time. The α-glucosidase inhibitory activity of six identified compounds was tested. The results show that compounds 1-6 show certain inhibitory activity with an IC_(50) value ranging from 8.2 to 33.5 µmol·L~(-1).

[Two new pinophol derivatives from endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal].

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).

Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function.

Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.

Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is essential for EBV episome maintenance, replication, and transcription. These effects are mediated by EBNA1 binding to cognate oriP DNA, which comprise 20 imperfect copies of a 30-bp dyad symmetry enhancer and an origin for DNA replication. To identify cell proteins essential for these EBNA1 functions, EBNA1 associated cell proteins were immune precipitated and analyzed by liquid chromatography-tandem mass spectrometry. Nucleolin (NCL) was identified to be EBNA1 associated. EBNA1's N-terminal 100 aa and NCL's RNA-binding domains were critical for EBNA1/NCL interaction. Lentivirus shRNA-mediated NCL depletion substantially reduced EBNA1 recruitment to oriP DNA, EBNA1-dependent transcription of an EBV oriP luciferase reporter, and EBV genome maintenance in lymphoblastoid cell lines. NCL RNA-binding domain K429 was critical for ATP and EBNA1 binding. NCL overexpression increased EBNA1 binding to oriP and transcription, whereas NCL K429A was deficient. Moreover, NCL silencing impaired lymphoblastoid cell line growth. These experiments reveal a surprisingly critical role for NCL K429 in EBNA1 episome maintenance and transcription, which may be a target for therapeutic intervention.

The nuclear chaperone nucleophosmin escorts an Epstein-Barr Virus nuclear antigen to establish transcriptional cascades for latent infection in human B cells.

Epstein-Barr Virus (EBV) is an oncogenic γ-herpesvirus that capably establishes both latent and lytic modes of infection in host cells and causes malignant diseases in humans. Nuclear antigen 2 (EBNA2)-mediated transcription of both cellular and viral genes is essential for the establishment and maintenance of the EBV latency program in B lymphocytes. Here, we employed a protein affinity pull-down and LC-MS/MS analysis to identify nucleophosmin (NPM1) as one of the cellular proteins bound to EBNA2. Additionally, the specific domains that are responsible for protein-protein interactions were characterized as EBNA2 residues 300 to 360 and the oligomerization domain (OD) of NPM1. As in c-MYC, dramatic NPM1 expression was induced in EBV positively infected B cells after three days of viral infection, and both EBNA2 and EBNALP were implicated in the transactivation of the NPM1 promoter. Depletion of NPM1 with the lentivirus-expressed short-hairpin RNAs (shRNAs) effectively abrogated EBNA2-dependent transcription and transformation outgrowth of lymphoblastoid cells. Notably, the ATP-bound state of NPM1 was required to induce assembly of a protein complex containing EBNA2, RBP-Jκ, and NPM1 by stabilizing the interaction of EBNA2 with RBP-Jκ. In a NPM1-knockdown cell line, we demonstrated that an EBNA2-mediated transcription defect was fully restored by the ectopic expression of NPM1. Our findings highlight the essential role of NPM1 in chaperoning EBNA2 onto the latency-associated membrane protein 1 (LMP1) promoters, which is coordinated with the subsequent activation of transcriptional cascades through RBP-Jκ during EBV infection. These data advance our understanding of EBV pathology and further imply that NPM1 can be exploited as a therapeutic target for EBV-associated diseases.

Clinical teaching competence inventory for nursing preceptors: instrument development and testing.

The aim of the study was to develop and test the psychometric properties of an instrument which measures clinical teaching competencies of nursing preceptors. It is necessary to investigate what kinds of teaching competencies are required in modern, more student-centered higher education teaching contexts. Nurses need to possess teaching competence to perform the role of preceptor properly. However, empirical studies exploring teaching competence are rare. Psychometric testing was conducted on a sample of 389 clinical nursing preceptors from three hospitals in 2010. Exploratory factor analysis and reliability testing were conducted on the 53-item Clinical Teaching Competencies Scale. Results indicated that principal axis factoring extraction identified four factors through a promax rotation: Student evaluation, goal setting and individual teaching, teaching strategies, and demonstration of organized knowledge. The Cronbach's α values for the four factors ranged from 0.82-0.87. The Clinical Teaching Competence Inventory was found to have adequate construct validity and internal consistency of reliability for clinical nursing preceptors to assess clinical teaching behaviors in practice settings.

The Influence of Dynamic Taping on Landing Biomechanics after Fatigue in Young Football Athletes: A Randomized, Sham-Controlled Crossover Trial.

Fatigue is believed to increase the risk of anterior cruciate ligament (ACL) injury by directly promoting high-risk biomechanics in the lower limbs. Studies have shown that dynamic taping can help normalize inadequate biomechanics during landings. This study aims to examine the effects of dynamic taping on landing biomechanics in fatigued football athletes. Twenty-seven high-school football athletes were recruited and randomly allocated to groups of either active taping or sham taping, with a crossover allocation two weeks later. In each group, the participants underwent a functional agility short-term fatigue protocol and were evaluated using the landing error scoring system before and after the fatigue protocol. The landing error scoring system (LESS) scores in the sham taping group increased from 4.24 ± 1.83 to 5.36 ± 2.00 (t = -2.07, p = 0.04, effect size = 0.61). In contrast, the pre-post difference did not reach statistical significance in the active taping group (from 4.24 ± 1.69 to 4.52 ± 1.69, t = -1.50, p = 0.15, effect size 0.46). Furthermore, the pre-post changes between the sham and active taping groups were statistically significant (sham taping: 1.12 ± 1.20; active taping: 0.28 ± 0.94, p = 0.007). Dynamic taping, particularly using the spiral technique, appeared to mitigate faulty landing biomechanics in the fatigued athletes by reducing hip and knee flexion and increasing hip internal rotation during landing. These results suggest that dynamic taping can potentially offer protective benefits in landing mechanics, which could further be applied to prevent ACL injuries in fatigued athletes.

Machine learning-based prediction of medication refill adherence among first-time insulin users with type 2 diabetes.

AIMS: The prevalence of Type 2 Diabetes Mellitus (T2DM) is projected to be 7 % in 2030. Despite its need for long-term diabetes care, the adherence rate of injectable medications such as insulin is around 60 %, lower than the acceptable threshold of 80 %. This study aims to create classification models to predict insulin adherence among adult T2DM naïve insulin users. METHODS: Clinical data were extracted from Taipei Medical University Clinical Research Database (TMUCRD) from January 1st, 2004 to December 30th, 2020. A patient was regarded as adherent if his/her medication possession ratio (MPR) was at least 80 %. Seven domains of predictors were created, including demographics, baseline medications, baseline comorbidities, baseline laboratory data, healthcare resource utilization, index insulins, and the concomitant non-insulin T2DM medications. We built two Xgboost models for internal and external testing respectively. RESULTS: Using a cohort of 4134 patients from Taiwan, our model achieved the Area Under the curve of the Receiver Operating Characteristic (AUROC) of the internal test was 0.782 and the AUROC of the external test was 0.771. the SHAP (SHapley Additive exPlanations) value showed that the number of prescribed medications, the number of outpatient visits, and laboratory data were predictive of future insulin adherence. CONCLUSIONS: This is the first study to predict adherence among adult naïve insulin users. The developed model is a potential clinical decision support tool to identify possible non-adherent patients for healthcare providers to design individualized education plans.

Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The ß of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

[Anti-apoptotic mechanism for p21(waf1) in human basal like breast cancer cell line HCC1937].

OBJECTIVE: To explore the anti-apoptotic mechanism of p21(waf1) in human basal like breast cancer cell line HCC1937. METHODS: There were 3 groups, i.e. experimental group HCC1937 with lentivirus -p21(waf1)-shRNA-RFP, control group 1 HCC1937 without lentivirus and control group 2 HCC1937 with lentivirus -RFP. The p21(waf1) and bim mRNA and protein expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. And apoptosis of HCC1937 in different groups was assayed by terminal deoxynucleotidyl transferase mediated C-dUTP nick end labeling (TUNEL). RESULTS: After interference with lentivirus-p21(waf1)-shRNA-RFP, p21(waf1) mRNA and protein expressions declined significantly in the experimental group versus the control groups (experiment group: 0.260 ± 0.004, 0.293 ± 0.006, control group 1: 0.879 ± 0.028, 0.483 ± 0.071, control group 2: 0.870 ± 0.025, 0.469 ± 0.047, all P < 0.01). The bim mRNA and protein expressions increased. And there was significant difference between the experiment and control groups (experiment group: 0.420 ± 0.013, 0.355 ± 0.007, control group 1: 0.258 ± 0.005, 0.142 ± 0.012, control group 2: 0.259 ± 0.002, 0.147 ± 0.013, all P < 0.001); apoptotic index increased (experiment group: 0.279 ± 0.012, control group 1: 0.145 ± 0.008, control group 2: 0.148 ± 0.012, both P < 0.001). CONCLUSION: In human basal-like breast cancer cell line HCC1937, p21(waf1) exerts anti-apoptotic activity by inhibiting the expression of bim, a mediator of mitochondrial apoptosis.

Combining Sequence Similarity with Physicochemical Properties to Predict Binders for MHC-II Molecules.

Prediction of binders of the major histocompatibility complex class II (MHC-II) molecules is critical for T cell immunogenicity. As protein-protein interaction also relies on physicochemical properties, we aim to build a novel model combining sequence information and the physicochemical properties of proteins. Our research used data from the NetMHCIIpan 3.2 study. Features include BLOSUM50 and the physicochemical properties from iFeature Python package. We created a hybrid model of recurrent neural layers and feedforward layers. The final Area Under the Receiver Operating Characteristics (AUROC) on the test data was 0.755.

EGCG debilitates the persistence of EBV latency by reducing the DNA binding potency of nuclear antigen 1.

Because the expression of EBNA1 is prevalent in all EBV-associated tumors, it has become one of the most attractive drug targets for the discovery of anti-EBV compounds. In a cell-based reporter system, EBNA1 consistently upregulated the transcription of an oriP-Luc mini-EBV episome by 6- to 8-fold. The treatment of cells with 50 µM EGCG effectively blocked the binding of EBNA1 to oriP-DNA both in vivo and in vitro, which led to the abrogation of EBNA1-dependent episome maintenance and transcriptional enhancement. Importantly, the anti-EBNA1 effects caused by EGCG ultimately impaired the persistence of EBV latent infection. Our data suggest that the inhibition of EBNA1 activity by EGCG could be a promising starting point for the development of new protocols for anti-EBV therapy.

Alerts in Clinical Decision Support Systems (CDSS): A Bibliometric Review and Content Analysis.

A clinical decision support system (CDSS) informs or generates medical recommendations for healthcare practitioners. An alert is the most common way for a CDSS to interact with practitioners. Research about alerts in CDSS has proliferated over the past ten years. The research trend is ongoing with new emerging terms and focus. Bibliometric analysis is ideal for researchers to understand the research trend and future directions. Influential articles, institutes, countries, authors, and commonly used keywords were analyzed to grasp a comprehensive view on our topic, alerts in CDSS. Articles published between 2011 and 2021 were extracted from the Web of Science database. There were 728 articles included for bibliometric analysis, among which 24 papers were selected for content analysis. Our analysis shows that the research direction has shifted from patient safety to system utility, implying the importance of alert usability to be clinically impactful. Finally, we conclude with future research directions such as the optimization of alert mechanisms and comprehensiveness to enhance alert appropriateness and to reduce alert fatigue.

Factors Influencing Pedestrian Smartphone Use and Effect of Combined Visual and Auditory Intervention on "Smombies": A Chinese Observational Study.

Objective: This was a large-scale multicenter study with two objectives. One was to study the factors influencing pedestrian smartphone use while crossing roads, and the other was to study the effect of combined visual and auditory intervention on smartphone zombies (smombies) at crossroads. Methods: This study was conducted in four different Chinese cities. By observing pedestrians crossing intersections, the weather, time, and characteristics of the pedestrians were recorded by four researchers. Then, its influencing factors and the effects of the intervention were studied in two consecutive periods. Results: A total of 25,860 pedestrians (13,086 without intervention and 12,774 with visual and auditory intervention) were observed in this study. Logistic regressions showed that gender, age of the pedestrians, weather, and time were the factors influencing smombies crossing roads. The number of smartphone users decreased from 4,289 to 3,579 (28.1%) (χ 2 = 69.120, p < 0.001) when the intervention was conducted. Conclusion: Based on large-sample, multicenter research, this study revealed the factors influencing pedestrian smartphone use while crossing roads, contributing to our understanding of the current situation of smombies in China. Furthermore, the effect of visual and auditory intervention was demonstrated, providing a new paradigm for global prevention of smombie behavior.

A Correlational Study of Acute Stress and Resilience Among Hospitalized Burn Victims Following the Taiwan Formosa Fun Coast Explosion.

Although the survival rate of burn patients in the Formosa Fun Coast Explosion disaster increased significantly, for patients facing long-term rehabilitation, there remained great stress. Therefore, the aim of this study was to explore the predictors of resilience among burn patients in this major disaster. We conducted a cross-sectional, descriptive study in a medical center in northern Taiwan, with a total of 30 burn patients enrolled. Patients' demographics were collected, and the Resilience Scale and Perceived Stress Scale were administered. Multivariate statistical analysis by stepwise and linear regression was used to test these predictors of resilience. The results showed that perceived stress was the key predictor of resilience in the stepwise regression analysis and by adjusting variables including stress level, gender, and education level. These results indicate that the stress level of burn patients should be determined first to provide more targeted methods for reducing stress and improving resilience.

Predictors of professional quality of life among nursing staff following the Taiwan Formosa Fun Coast explosion.

PURPOSE: The Formosa Fun Coast Explosion was a major public disaster that caused international shock. Nursing staff made an all-out effort to care for patients injured in the explosion, and this may have caused a lot of stress among nurses. This study aimed to explore the predictors of professional quality of life among nursing staff experiencing major disaster events. MATERIAL AND METHODS: This descriptive cross-sectional study was conducted in a medical center in Northern Taiwan in 2016. A total of 165 nurses were enrolled using convenience sampling. Data were collected on the demographic- and work-related characteristics of nurses, and the Perceived Stress Scale and Professional Quality of Life Scale were administered. Analyses included descriptive statistics and regression. The threshold for statistical significance was set at p<0.05. RESULTS: The nurses' length of service in nursing (ß=-0.26, p=0.029) and perceived stress level (ß=0.15, p=0.002) were important predictors of compassion satisfaction, while their age (ß=0.42, p=0.033) and perceived stress level (ß=0.20, p=0.020) were important predictors of compassion fatigue. Compassion fatigue was divided into burnout and secondary trauma. Nurses' age (ß=0.18, p=0.044) and perceived stress level (ß=0.14, p<0.001) were the key predictors of burnout. However, there were no significant predictors of secondary trauma among nurses. CONCLUSIONS: Based on the present findings, it is proposed to reduce the level of stress among nurses to improve their professional quality of life.

Comparison of Multivariable Logistic Regression and Other Machine Learning Algorithms for Prognostic Prediction Studies in Pregnancy Care: Systematic Review and Meta-Analysis.

BACKGROUND: Predictions in pregnancy care are complex because of interactions among multiple factors. Hence, pregnancy outcomes are not easily predicted by a single predictor using only one algorithm or modeling method. OBJECTIVE: This study aims to review and compare the predictive performances between logistic regression (LR) and other machine learning algorithms for developing or validating a multivariable prognostic prediction model for pregnancy care to inform clinicians' decision making. METHODS: Research articles from MEDLINE, Scopus, Web of Science, and Google Scholar were reviewed following several guidelines for a prognostic prediction study, including a risk of bias (ROB) assessment. We report the results based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were primarily framed as PICOTS (population, index, comparator, outcomes, timing, and setting): Population: men or women in procreative management, pregnant women, and fetuses or newborns; Index: multivariable prognostic prediction models using non-LR algorithms for risk classification to inform clinicians' decision making; Comparator: the models applying an LR; Outcomes: pregnancy-related outcomes of procreation or pregnancy outcomes for pregnant women and fetuses or newborns; Timing: pre-, inter-, and peripregnancy periods (predictors), at the pregnancy, delivery, and either puerperal or neonatal period (outcome), and either short- or long-term prognoses (time interval); and Setting: primary care or hospital. The results were synthesized by reporting study characteristics and ROBs and by random effects modeling of the difference of the logit area under the receiver operating characteristic curve of each non-LR model compared with the LR model for the same pregnancy outcomes. We also reported between-study heterogeneity by using τ2 and I2. RESULTS: Of the 2093 records, we included 142 studies for the systematic review and 62 studies for a meta-analysis. Most prediction models used LR (92/142, 64.8%) and artificial neural networks (20/142, 14.1%) among non-LR algorithms. Only 16.9% (24/142) of studies had a low ROB. A total of 2 non-LR algorithms from low ROB studies significantly outperformed LR. The first algorithm was a random forest for preterm delivery (logit AUROC 2.51, 95% CI 1.49-3.53; I2=86%; τ2=0.77) and pre-eclampsia (logit AUROC 1.2, 95% CI 0.72-1.67; I2=75%; τ2=0.09). The second algorithm was gradient boosting for cesarean section (logit AUROC 2.26, 95% CI 1.39-3.13; I2=75%; τ2=0.43) and gestational diabetes (logit AUROC 1.03, 95% CI 0.69-1.37; I2=83%; τ2=0.07). CONCLUSIONS: Prediction models with the best performances across studies were not necessarily those that used LR but also used random forest and gradient boosting that also performed well. We recommend a reanalysis of existing LR models for several pregnancy outcomes by comparing them with those algorithms that apply standard guidelines. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42019136106; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=136106.

OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models.

AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplantation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors.

Electro-acupuncture improves survival and migration of transplanted neural stem cells in injured spinal cord in rats.

This study investigated whether electro-acupuncture (EA) would improve the survival and migration of neural stem cells (NSCs) transplanted in injured spinal cord as well as the potential mechanisms. T10 spinal cord segments of 50 adult Sprague-Dawley (SD) rats were completely transected, and then NSCs were immediately transplanted into the transected site of the experimental animals, while control animals were sham operated without transplantation. Five days post-operation, electro-acupuncture treatment on GV9 (Zhiyang), GV6 (Jizhong), GV2 (Yaoshu) and GV1 (Changqiang) acupoints was applied for 14 days (EA+NSCs 14d) and 30 days (EA+NSCs 30d). ELISA and immunohistochemical staining were used to assess the content of neurotrophine-3 (NT-3) and the characteristics of transplanted NSCs. We found that the number of transplanted NSCs the survived in EA+NSCs14d group was significantly increased as compared to that of the NSCs30d group (5825.20 +/- 819.01 vs 4781.40 +/- 500.49, P<0.05). Immunostaining indicated that some transplanted NSCs developed into microtubule association protein 2 (MAP2) positive cells and many of them developed into glial fibrillary acidic protein (GFAP) positive cells in the NSCs30d group. Further, the migration length of transplanted NSCs toward caudal tissue in the injured site was longer in the EA+NSCs30d group than that in NSCs30d group (5.98 +/- 0.79 mm vs 3.96 +/- 1.72 mm; P<0.05). Also NT-3 in injured spinal cord tissue was 23% increased in the EA+NSCs14d group. These results suggest that the combination of EA and NSCs improves the survival and migration of NSCs in injured spinal cord in rats.

Expression spectra of matrix metalloproteinases in metastatic non-small cell lung cancer.

By combining suppression subtractive hybridization and microarray to examine gene expressions between metastatic and non-metastatic non-small cell lung cancer (NSCLC), we have identified differential expression spectra of matrix metalloproteinases (MMP). Among MMPs, expressions of MMP-13, -14, -15 and -24 decreased, those of MMP-9, -11, -12, -16, -17, -19 and -23B did not change, and those of MMP-1, -2, -7, -8 and -10 increased dramatically. Overexpressions of MMP-1, -2, -7 and -10 were confirmed by reverse transcription-polymerase chain reaction. In this study we further assessed the clinical significance of MMP-1, -2, -7 and -10. Specimens from 472 patients with completely resected NSCLC were examined by immunohistochemistry. The median follow-up period was 38 months (range, 2-113 months). Overexpression of MMP-1 was observed in 72.9% (n=344) of 472 patients, that of MMP-2 was 77.9% (n=352), MMP-7 63.3% (n=299) and that of MMP-10 was 27.1% (n=128). For patients with lymph node metastasis, MMP-1 and -2 overexpressions were not only independent prognostic factors for unfavorable outcome, but also associated with decreased survival (p=0.0015, and p=0.011 respectively). The present study showed that MMP expression spectrum in NSCLC was heterogeneous: expression of some MMP increased, some unchanged, while some decreased. Therefore, it should be worth determining MMP expression pattern as a regimen reference for NSCLC patients who were scheduled to receive MMP inhibitor, which was class-specific, as adjuvant therapeutic agent.