Search

Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus propofol-based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double-blinded study was conducted in three teaching hospitals in China. Patients receiving on-pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0-1.5 MAC) or propofol (2.0-3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7-14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol-based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval [CI]: 0.38-0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% [35/144] vs. 25.9% [35/145], 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 [0.9) vs. 3 (1.0], 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on-pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.

There are two source plants for the traditional Chinese medicine Murrayae Folium et Cacumen (MFC) in Chinese Pharmacopoeia, i.e. Murraya exotica L. and M. paniculata (L.) Jack. Herein, a chemical comparison of M. exotica and M. paniculata by high performance liquid chromatography (HPLC) fingerprint analysis coupled with chemometrics and network pharmacology was performed. The main peaks in the fingerprints were identified by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) and authenticated by references. The chemometrics results showed that the HPLC fingerprints of these two species were clearly divided into two categories using hierarchical cluster analysis (HCA) and principal component analysis (PCA), and a total of 13 significantly differentiated markers were screened out by orthogonal partial least squares-discriminant analysis (OPLS-DA). However, the following network pharmacology analysis showed that these discriminated markers were found to act via many common targets and metabolic pathways, indicating the possibly similar pharmacological effects and mechanisms for M. exotica and M. paniculata. The above results provide valuable evidence for the equivalent use of these two plants in clinical settings. Moreover, the chromatographic fingerprint analysis coupled with chemometrics and network pharmacology supplies an efficient approach for the comparative analysis of multi-source TCMs like MFC.

Rationale, aims and objectives: To determine current practices, attitudes and demands of Chinese anesthesiologists regarding depth of anesthesia (DoA) monitoring. Method: An anonymous online survey was randomly distributed to 8,556 anesthesiologists. Results: The overall response rate was 47% (4,037 respondents). Only 9.1% (95% confidence interval, 8.2%-10.0%) of the respondents routinely use DoA monitors. The main factors influencing the utility of DoA monitors were poor anti-interference ability (56.0%, 54.5%-57.6%), inability to bill insurance or high cost (55.5%, 54.0%-57.0%), limited accuracy (47.9%, 46.3%-49.4%) and inability to monitor analgesic effects (35.7%, 34.2%-37.1%). Academic respondents (91.5%, 90.3%-92.7%) primarily used DoA monitoring to prevent awareness, whereas nonacademic respondents (88.8%, 87.4%-90.2%) primarily used DoA monitoring to guide the delivery of anesthetics. In total, the respondents who had not used a DoA monitor and experienced awareness (61.7%, 57.8%-65.6%) was significantly greater than those who had used one or several DoA monitors (51.5%, 49.8%-53.2%). However, most respondents (95.7%, 95.1%-96.3%) demanded improvements in the accuracy of the monitors for DoA monitoring and a broad application in patients of all ages (86.3%, 85.2%-87.4%), analgesia monitoring (80.4%, 79.2%-81.6%) and all types of anesthetics (75.6%, 74.3%-76.9%). In total, 65.0% (63.6%-66.5%) of the respondents believed that DoA monitors should be combined with EEG and vital sign monitoring, and 53.7% (52.1%-55.2%) believed that advanced DoA monitors should include artificial intelligence. Conclusions: Academic anesthesiologists primarily use DoA monitoring to help prevent awareness, whereas nonacademic anesthesiologists use DoA monitoring to guide the delivery of anesthetics. Regardless of whether a DoA monitor is used, anesthesiologists believe that DoA monitoring could help to reduce the incidence of awareness. Anesthesiologists demand high-accuracy DoA monitors incorporating signals of EEG, multiple vital signs and antinociceptive indicators. DoA monitors with artificial intelligence may represent a new direction for future research on DoA monitoring.

Cholangiocarcinoma (CCA) is a fatal disease with dismal survival rates. Long non-coding RNA (lncRNA) expression profiling as potential prognostic biomarkers play critical roles in tumor initiation, development, and poor prognosis. Identifying specific lncRNA to predict the prognosis of CCA patients in the early stages is very important for improving a patient’s survival. In the current study, we aimed to establish a novel risk-stratification lncRNA signature panel in CCA. The initial lncRNA discovery was identified in The Cancer Genome Atlas database (TCGA cohort). The Cox regression analysis was used to establish the lncRNA prognostic model and the receiver operating characteristic (ROC) curve analysis was performed to assess the specificity and sensitivity of the model. This was followed by independent validation of the lncRNA signature in the CCA patients from the First Affiliated Hospital of Wenzhou Medical University (WMU cohort). Furthermore, by using the Gene Ontology function and Kyoto Encyclopedia Gene and Genome pathway enrichment analysis, we explored the potential function of prognosis lncRNA. Finally, five lncRNA (HULC; AL359715.5; AC006504.8; AC090114.2; AP00943.4) were screened to establish the predictive model that significantly associated with poor overall survival(HR:4.879;95%CI,1.587-14.996;p=0.006). This five-lncRNA signature model showed excellent accuracy in the TCGA cohort (AUC=0.938), and also robustly predicted survival in the validation WMU cohort(AUC=0.816). Functional enrichment analysis suggested prognostic lncRNA was primarily associated with CCA-related biological processes. Our data established a novel lncRNA signature model for CCA risk-stratification and robust identification of CCA patients with poor molecular genotypes. Moreover, it revealed new molecular mechanisms of CCA.

The global morbidity and mortality of heart failure has been increasing in recent years. Traditional Chinese medicine (TCM) was increasingly used to treat cardiovascular diseases. Baoyuan decoction (BYD) was a famous classical prescription in China. Modern pharmacological studies showed that it had obvious therapeutic effects on cardiovascular diseases, but its pathological pharmacokinetic studies were unclear. In this research, the absorption of 16 bioactive components in plasma and the excretion of 9 representative components in urine of control rats and isoproterenol (ISO)-induced heart failure rats were studied using the large-volume direct-injection LC-MS method established by our research group. The results indicated that flavonoid constituents exhibited quicker absorption and elimination than saponin constituents after oral administration of BYD. The half-life period of some bioactive compounds in the model group was increased, which contributed to the longer therapeutic effect. The cumulative excretion rate of major flavonoid components of BYD decreased significantly in the ISO-induced heart failure rats.

Single-site laparoscopic percutaneous extraperitoneal ligation (SLPEL) for pediatric inguinal hernia gained popularity all over the world. However, complications associated with extraperitoneal knotting were not rare in the classical SLPEL(C-SLPEL) procedure. In order to overcome disadvantages, we herein developed the modified SLPEL (M-SLPEL) procedure, intact circuit ligation of the peritoneum around the internal ring using a homemade hernia needle with a single abdominal wall centesis. To evaluated the effectiveness of the M-SLPEL procedure to decrease adverse events associated with ligation knotting, a comparative study was carried out. A total of 3219 patients from multiple centers were divided into two groups according to the operative procedures: M-SLPEL group and C-SLPEL group. All patients were followed up. Data describing the clinical characteristics, operative time, postoperative hospital stay, and complications was collected and retrospectively analyzed. With equivalent operative time, postoperative hospital stay, there was statistically significant difference between two groups in terms of the overall complications incidence (2.6% in C-SLPEL Vs 0.11% in M-SLPEL, P=0.03), including pain in inguinal area, knot foreign body reaction, palpable knot, recurrence. Together, these findings suggest that the M-SLPEL procedure is an effective and safe approach, with unique advantage in reducing adverse events in the inguinal region.

Background: Estimating the depth of anaesthesia (DoA) is critical in clinical anaesthesiology. Electroencephalograms (EEGs) have been widely used for monitoring the DoA; however, they may be inaccurate under certain conditions. Methods: In this study, we propose a novel method to evaluate the DoA based on multiple heart rate variability (HRV)-derived features combined with a discrete wavelet transform and deep neural networks (DNNs). Four features were extracted from an electrocardiogram, including the HRV high-frequency power, low-frequency power, high-to-low-frequency power ratio, and sample entropy. Next, these features were used as inputs for the DNN, which used the expert assessment of consciousness level as the reference output. Finally, the DNN was compared with the logistic regression (LR), support vector machine (SVM), and decision tree (DT) models. The data of 23 anaesthesia patients were used to assess the proposed method. Results: The results demonstrated that the accuracies of the four models, in distinguishing the anaesthesia states, were 86.2% (LR),87.5% (SVM),87.2% (DT), and 90.1%(DNN). Our method outperformed the LR, SVM, and DT methods.Conclusions: The proposed method could accurately distinguish between different anaesthesia states, thus, providing an alternative or supplementary method to EEG monitoring for the assessment of DoA.

In modern chemical processes, varieties of fault detection and diagnosis methods have been used for ensuring process safety and product quality widely. As an important branch, fault detection and diagnosis methods based on data-driven are effective in large-scale chemical processes. However, they do not often show superior performance owing to the self-limitations and the characteristics of process data, such as nonlinearity, non-Gaussian, and multi-operating mode. To cope with these issues, k-NN (k-Nearest Neighbor) fault detection method and its extension have been developed in recent years. Nevertheless, these methods are used for fault detection mainly, few papers can be found about fault diagnosis. In this paper, a novel abnormal variables identification method is proposed, this method uses k-NN distance contribution analysis theory to evaluate which variables are most likely to be abnormal, meanwhile, the feasibility of this method is verified by contribution decomposition theory. The proposed search strategy can guarantee that all abnormal variables are found in each sample. The reliability and validity of the proposed method are verified by a numerical example and the Continuous Stirred Tank Reactor system.

// Qian Zhu 1, * , Guo-Liang Qiao 2, * , Xiao-Chuan Zeng 1, * , Yun Li 1 , Jian-Jun Yan 3 , Rui Duan 1 , Zhi-Yong Du 4 1 Department of General Surgery, Jingmen First People's Hospital, Jingmen 448000, Hubei Province, China 2 Department of Medical Oncology, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Beijing, 100038, China 3 First Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China 4 Department of Hepatobiliary Surgery, Central Hospital of Wuhan, Wuhan 430014, Hubei Province, China * These authors have contributed equally to this work Correspondence to: Zhi-Yong Du, email: duzhiyong88@163.com Rui Duan, email: duanrui@sina.com Keywords: hepatocellular carcinoma, initiation factors, microarray, prognosis, tumor progression Received: October 07, 2015 Accepted: June 04, 2016 Published: June 22, 2016 ABSTRACT Aim: We studied the role of eukaryotic translation initiation factor 3 subunit H (EIF3H) in hepatocellular carcinoma (HCC) progression. Results: High EIF3H expression was observed in 50.23% patients. Upregulation of EIF3H is an independent predictor for greater rates of cancer recurrence and shorter overall survival in HCC patients. Knockdown of EIF3H expression in HCC cells promoted apoptosis, and inhibited cell growth, colony formation, migration, as well as xenograft growth. TGF-βand MAPK pathways are potentially targeted by EIF3H. Methods: EIF3H mRNA expression was measured in HCC tissue samples and paired non-tumor samples (N=60) and results were validated in another dataset of 215 HCC patients. Then EIF3H expression and clinical outcomes were correlated. Malignant phenotypes were studied after EIF3H expression was knocked down with siRNA in HCC cell lines. EIF3H targeted pathways were identified by microarray analysis. Conclusion: EIF3H is frequently upregulated and is an independent prognostic marker for HCC patients and EIF3H inhibition mitigates the malignant phenotype. Our data provide novel insight into the function of EIF3H in HCC progression, and suggest that EIF3H may be a potentially valuable biomarker for HCC.

Brooding is a major breeding investment of parental birds during the early nestling stage, and has important effects on the development and survival of nestlings. Investigating brooding behavior can help to understand avian breeding investment strategies. From January to June in 2013 and 2014, we studied the brooding behaviors of long-tailed tits (Aegithalos caudatus glaucogularis) in Dongzhai National Nature Reserve, Henan Province, China. We analyzed the relationships between parental diurnal brooding duration and nestling age, brood size, temperature, relative breeding season, time of day and nestling frequencies during brooding duration. Results showed that female and male long-tailed tit parents had different breeding investment strategies during the early nestling stage. Female parents bore most of the brooding investment, while male parents performed most of the nestling feedings. In addition, helpers were not found to brood nestlings at the two cooperative breeding nests. Parental brooding duration was significantly associated with the food delivered to nestlings (F=86.10, df=1, 193.94, P

Myocardial ischemia (MI) is an escalating public health care burden worldwide. Baoyuan decoction (BYD) is a traditional Chinese medicine formula with cardioprotective activity; however, its pharmacological characteristics and mechanisms are obscured. Herein, a multi-omics strategy via incorporating the metabonomics, transcriptomics, and pharmacodynamics was adopted to investigate the effects and molecular mechanisms of BYD for treating MI in a rat model of left anterior descending coronary artery (LADCA) ligation. The results indicated that BYD has a significantly cardioprotective role against MI by decreasing the infarct size, converting the echocardiographic abnormalities and myocardial enzyme markers, and reversing the serum metabolic disorders and myocardial transcriptional perturbations resulting from MI. Integrated bioinformatics analysis and literature reports constructed the interaction network based on the changes of the key MI targeted-metabolites and transcripts after BYD treatment and disclosed that the cardioprotection of BYD is mainly involved in the regulation of energy homeostasis, oxidative stress, apoptosis, inflammation, cardiac contractile dysfunction, and extracellular matrix remodeling. The results of histopathological examination, quantitative RT-PCR assay, cardiac energy synthesis, and serum antioxidant assessment complemented the multi-omics findings, and indicated the multi-pathway modulation mechanisms of BYD. Our investigation demonstrated that the multi-omics approach could achieve a complementary and verified view for the comprehensive evaluation of therapeutic effects and complex mechanisms of TCMF like BYD.

Transarterial embolization (TAE) is a palliative option commonly used for the treatment of advanced, unresectable hepatocellular carcinoma (HCC). However, patient prognosis in regards to overall survival has not improved with this method, mainly due to hypoxia-inducible factor-1α (HIF-1α)-induced angiogenesis and invasiveness. Thus, it is hypothesized that HIF-1α may be an ideal knockout target for the treatment of HCC in combination with TAE. Thus, in the present study, HIF-1α knockout was conducted in human liver cancer SMMC-7721 cells and a xenograft HCC model was established using a lentivirus-mediated CRISPR/Cas system (LV-Cas) with small guide RNA-721 (LV-H721). Furthermore, hepatic artery ligation (HAL) was used to mimic human transarterial chemoembolization in mice. The results revealed that HIF-1α was highly expressed in both HCC patient tissues and SMMC-7721-induced tumor tissues. The HIF-1α knockout in SMMC-7721 cells significantly suppressed cell invasiveness and migration, and induced cell apoptosis under CoCl2-mimicking hypoxic conditions. Compared with the control groups, HAL + LV-H721 inhibited SMMC-7721 tumor growth in orthotopic HCC and markedly prolonged the survival of HCC-bearing mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and increased apoptosis in the tumor cells. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9-mediated HIF-1α knockout with TAE in mice and highlighted the possibility that HIF-1α may be an effective therapeutic knockout target in combination with TAE for HCC treatment.

Background: There is increasing evidence that long non-coding RNA are involved in the occurrence and progression of various tumors as carcinogenic or tumor suppressor regulators. Aims: Our study purposed to identify a novel lncRNA signature panel and evaluate its predictive value on cholangiocarcinoma (CCA) prognosis. Methods: Differentially expressed lncRNA were identified in CCA patients from The Cancer Genome Atlas database. The "edgeR" package and Cox regression analysis was used to establish a lncRNA prognostic model, which allowed patients to be divided into high-risk and low-risk groups. Through Receiver operating curves analysis, 90 CCA patients from the First Affiliated Hospital of Wenzhou Medical University (WMU) was performed to investigate the specificity and sensitivity of the model. By using Gene Ontology function and Kyoto Encyclopedia Gene and Genome pathway enrichment analysis, we explored the potential function of prognosis lncRNA. Results: A total of 1192 differential expression of lncRNA were identified in CCA and normal tissues. Five lncRNAs (HULC; AL359715.5; AC006504.8; AC090114.2; AP00943.4) were screened to establish a predictive model, whose high predictive power was validated in 90 CCA patients from WMU. Further analysis showed the independent prognostic capability of 5-lncRNA in the model, which had high sensitivity and specificity. Moreover, functional enrichment analysis suggested prognostic lncRNAs were primarily associated with CCA-related various biological processes. Conclusions: Our data established a novel lncRNA prognostic model for CCA, provided prognostic more useful information that went beyond traditional clinical pathology to predict survival in CCA patients. In addition, it revealed new molecular mechanisms of CCA. Funding: This work was supported by the grants from the Natural Science Foundation of Zhejiang Province (LY17H160047), the Public Projects of Zhejiang Province (2016C37127, 2018C37114), the National Natural Science Foundation of China (81470868, 81772628, 81703310). Declaration of Interest: The authors declare no conflict of interests. Ethical Approval: This study was approved by WMU’s Ethics Committee.

Myocardial energy expenditure (MEE) and 2-oxoglutarate are elevated in chronic heart failure (CHF) patients compared with healthy controls. To explore whether 2-oxoglutarate could reflect the levels of MEE and predict the prognosis of CHF, 219 CHF patients and 66 healthy controls were enrolled. 2-Oxoglutarate was assayed with Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC/MS/MS). CHF patients were divided into 4 groups according to interquartile range of MEE and followed for death or recurrent hospital admission due to CHF for the mean follow-up time 6.64±0.16months. 2-Oxoglutarate was increased in CHF patients compared with controls (P

Data-driven fault detection and identification methods are important in large-scale chemical processes. However, some traditional methods often fail to show superior performance owing to the self-limitations and the characteristics of process data, such as nonlinearity, non-Gaussian distribution, and multi-operating mode. To cope with these issues, the k-NN (k-Nearest Neighbor) fault detection method and extensions have been developed in recent years. Nevertheless, these methods are primarily used for fault detection, and few papers can be found that examine fault identification. In this paper, in order to extract effective fault information, the relationship between various faults and abnormal variables is studied, and an accurate &ldquo, fault&ndash, symptom&rdquo, table is presented. Then, a novel fault identification method based on k-NN variable contribution and CNN data reconstruction theories is proposed. When there is an abnormality, a variable contribution plot method based on k-NN is used to calculate the contribution index of each variable, and the feasibility of this method is verified by contribution decomposition theory, which includes a feasibility analysis of a single abnormal variable and multiple abnormal variables. Furthermore, to identify all the faulty variables, a CNN (Center-based Nearest Neighbor) data reconstruction method is proposed, the variables that have the larger contribution indices can be reconstructed using the CNN reconstruction method in turn. The proposed search strategy can guarantee that all faulty variables are found in each sample. The reliability and validity of the proposed method are verified by a numerical example and the Continuous Stirred Tank Reactor system.

Objective: To summarize our experience in the anesthetic management of conjoined twins undergoing one-stage surgical separation. Methodology: Medical records of conjoined twins admitted to our hospital for treatment and considered for surgical separation from 1996 to present were retrospectively reviewed. Four cases of conjoined twins underwent one-stage surgical separation under general anesthesia. Preoperative evaluation was performed to determine the extent of anatomical conjunction and associated anomalies. Anesthesia was simultaneously induced in all conjoined twins. The intubation procedure was successfully performed with the head slightly rotated to each baby’s side, followed by the administration of vecuronium. Anesthetic agents were administered according to the estimated weight of each baby. One case of conjoined twins underwent surgical separation with cardiopulmonary bypass due to shared hearts. Results: All conjoined twins were successfully separated. No significant respiratory or cardiac events occurred during surgery except for one twin, which died after separation because of complicated congenital heart disease. Conclusions : Accurate preoperative evaluation, respiratory and circulatory management, and close cooperation of the multidisciplinary team are important aspects of anesthetic management of conjoined twins surgery.

Brooding is a major breeding investment of parental birds during the early nestling stage, and has important effects on the development and survival of nestlings. Investigating brooding behavior can help to understand avian breeding investment strategies. From January to June in 2013 and 2014, we studied the brooding behaviors of long-tailed tits (Aegithalos caudatus glaucogularis) in Dongzhai National Nature Reserve, Henan Province, China. We analyzed the relationships between parental diurnal brooding duration and nestling age, brood size, temperature, relative breeding season, time of day and nestling frequencies during brooding duration. Results showed that female and male long-tailed tit parents had different breeding investment strategies during the early nestling stage. Female parents bore most of the brooding investment, while male parents performed most of the nestling feedings. In addition, helpers were not found to brood nestlings at the two cooperative breeding nests. Parental brooding duration was significantly associated with the food delivered to nestlings (F=86.10, df=1, 193.94, P

Recent studies suggest that the ability to form and grow tumors specifically resides in a small cell population called cancer stem cells (CSCs). These studies were conducted mainly on various human cancers; however, isolation and characterization of stem cells from cholangiocarcinoma have not been attempted. The molecular markers CD24, CD44, CD34, and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of CSCs. In this study, we used these markers to identify a subpopulation of cells in extrahepatic cholangiocarcinoma (ECC) with cancer stem/progenitor cell-like properties. We found that CD24(+) CD44(+) EpCAM(high) cells (0.39-2.27%) were present in human ECC tissues. The expression of a CD24(+) CD44(+) EpCAM(high) subpopulation was consistent with primary cancers and could be duplicated during serial in vivo passaging in NOD/SCID mice. CD24(+) CD44(+) EpCAM(high) cells isolated from 3 cholangiocarcinoma xenografts showed high tumorigenic potential compared with CD24(-) CD44(-) EpCAM(low/-) cells. These tumorigenic ECC cells exhibited the stem cell properties of self-renewal and ability to produce heterogeneous progeny. We report the identification of a CSC population in ECC characterized by CD24, CD44 and EpCAM phenotypes. Our findings could provide new insight into the tumorigenesis of cholangiocarcinoma and offer a potential target for anti-cancer therapy.

Soft sensing technology is one of the topics of general interest in study on current process control, which has recently drawn considerable attention worldwide, and has stimulated researchers and engineers to make greater effort to reduce the cost/benefit-ratio for development and manufacture of bio-industrial processes both economically and environmentally. This paper introduced a kind of soft-sensor based on an improved support vector machine (SVM) for a polyacrylonitrile productive process. The improved SVM called the multiple kernel support vector machine was presented, and the mathematical formulation of multiple kernel learning is given. Through the implementation for average molecular weight in polyacrylonitrile productive process, it demonstrates the good performance of the proposed method compared to single kernel.

To investigate whether the side population cells (SP cells) exist in human gallbladder carcinoma cell line and the differences of drug resistance gene ABCG2 expression in SP cells, non-SP cells and GBC-SD cell lines. Fluorescence activated cell sorter (FACS) was used to sort the SP and non-SP cells from GBC-SD cell line of gallbladder carcinoma of human being. Then, the sorting cells were cultured and detected the expression of ABCG2 gene among the SP cells, non-SP cells and GBC-SD cell lines by using reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence chemistry, western blot and flow cytometry techniques. A very small fraction cells (0.64 ± 0.08%) were isolated through FACS analysis which had the potency of stem cells and highly expressed ABCG2 gene (89.56 ± 3.86%). On the contrary, there were nearly no expression in non-SP cells (1.32 ± 0.49%) and lower expression in GBC-SD cell line (12.37 ± 1.61%). The side population cells that had the potency of stem cells existed in human gallbladder carcinoma cell line and over-expressed the drug resistance gene ABCG2. They may be play an important role in drug resistance of tumor.

Objective To investigate the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene transfection mediated by adenovirus into human pancreatic carcinoma cell line Panc-1, and the mechanisms involved in this effect.

A comparative proteomic approach has been used to identify and analyze proteins related to pancreatic cancer. Proteomes of eight pairs of clinical pancreatic ductal adenocarcinoma (PDAC) tissue samples and samples of normal adjacent tissue were obtained by two-dimensional gel electrophoresis (2DE). Comprehensive analysis of proteins was focused on total protein spots for which there were statistical differences between the two groups. Proteins were identified by peptide mass fingerprinting with tandem mass spectrometry (MS-MS). Western blotting and immunohistochemistry (IHC) were also performed to verify the expression of some candidate proteins. Thirty protein spots were identified, including proteases, antioxidant proteins, signal-transduction proteins, calcium-binding proteins, structural proteins, chaperones, and others. Western blotting and IHC confirmed up-regulated expression of two candidate proteins, nucleotide diphosphatase kinase (NDPK) and annexin II, in tumorous tissues. These results suggest that combination of 2DE with MS is an effective strategy for discovery of differently expressed proteins in PDAC which may be molecular markers for diagnosis or therapeutic targets.

To investigate the feasibility of applying (1)H-NMR-based pattern recognition in the studies of serum metabonomics in chronic heart failure (HF).(1)H-NMR technique was applied for examination of the serum samples from 9 patients with chronic heart failure and 6 healthy individuals. The data were analyzed for pattern recognition through principal component analysis (PCA) and Orthogonal Partial Least Square (OPLS) to determine the differences in serum metabolites between the two groups. The recognition ability of the two analysis methods were compared.The serum (1)H-NMR spectra of heart failure patients and healthy individuals were significantly different. The PCA method failed to distinguish the patterns between the two groups, but OPLS clearly differentiated the two groups.(1)H-NMR technique is effective in the study of serum metabolomics in chronic heart failure. The serum metabonomics of patients with chronic heart failure and the healthy individuals are significantly different. OPLS pattern recognition method is superior to PCA method in that the former can remove the influence of non-experimental factors and provide an improved characterization.

To investigate the morning blood pressure surge (MBPS) and its relationship with 24-hour blood pressure variability and anti-hypertensive drugs in middle-aged and elderly hypertensive patients.A total of 521 middle-age and elderly men were surveyed with ambulatory blood pressure monitoring and ambulatory electrocardiograms recordings as well as questionnaire investigation from January 2009 to December 2010. Subjects were divided into MBPS positive group and MBPS negative group according to the level of MBPS [35 mm Hg (1 mm Hg = 0.133 kPa) or ≤ 35 mm Hg].In all the cases, the prevalence of MBPS was 19.4%, of which the elderly and very elderly had higher prevalences (18.9% and 21.8%, respectively) than the middle-aged (5.6%, both P0.01). Significant differences could be found in age[(81.6 ± 6.4) years vs (78.7 ± 9.7) years], day mean systolic blood pressure [(132.8 ± 13.3) mm Hg vs (128.8 ± 13.3) mm Hg], fasting blood glucose [(5.96 ± 1.59) mmol/L vs (5.68 ± 1.22) mmol/L] and 24-hour blood pressure variability between the two groups (all P0.05). Significant difference could be observed in the prevalence of MBPS between the diuretics-taking group and non-taking group (27.4% vs 17.6%, P0.05).The elderly hypertensive patients are prone to appear MBPS phenomenon. Fasting blood glucose level, 24-hour blood pressure variability may be associated with MBPS. Diuretic antihypertensive treatment may not be conductive for MBPS control.

To evaluate the relationship between myocardial energy expenditure (MEE) level and cardiac function in chronic heart failure (CHF) patients.A total of 99 CHF patients were divided into 3 groups according to the LVEF (HFNEFor = 50%, n = 37; HFREF1 35.1% - 49.9%, n = 30; HFREF2or = 35%, n = 32) or the New York Heart Association (NYHA II, n = 26; III, n = 42; IV, n = 31) criteria. Thirty patients with cardiovascular disease and without CHF served as controls. Routine examinations including serum CRP (ELISA) and plasma NT-proBNP (chemiluminescence sandwich ELISA) were made on the next morning after admission; echocardiography was performed on the third day after admission. LVMW, LVMWI, RWT, LVIDd, LA, LV, LVEF, LVFS, E/A, EDT, IVRT, Tei index and MEE were measured or calculated.MEE was significantly higher in HFREF patients than in controls (P0.01) and similar between HFNEF patients and controls (P0.05). MEE increased in proportion to decrease of LVEF and increase of NYHA grades in CHF patients (all P0.05). Bivariate analysis confirmed that MEE was significant correlated with LVMW, LVMWI, RWT, LVIDd, LA, LV, LVEF (r = -0.540, P0.01), LVFS (r = -0.454, P0.01), E/A, EDT, IVRT, Tei index, NYHA grades, CRP and NT-proBNP.MEE derived from standard echocardiographic measurements is an effective indicator for myocardial bioenergetics and significantly correlated with cardiac function in CHF patients, especially in CHF patients with reduced LVEF.

To investigate whether terbutaline affects alveolar liquid clearance after oleic acid-induced lung injury in rats.Forty healthy Wistar rats (weighing 250-280 g) were randomly divided into five groups (n=8 in each group): the normal control group (control group), oleic acid injury group (injury group), terbutaline-treated group (terbutaline group), terbutaline plus amiloride-treated group (terbutaline+amiloride group) and terbutaline plus ouabain-treated group (terbutaline+ouabain group). Acute lung injury model was induced by intravenous oleic acid (0.25 ml/kg body weight). 24 hours later, 1.5 microCi (125) I-labeled 5% albumin solution (5 ml/kg body weight) was dripped into the lungs through trachea. The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter.At 24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with the alveolar liquid clearance rate decreased by 49.2% and the extravascular lung water content elevated by 47.9%. Compared with the rats in the injury group, terbutaline (10(-4) mol/L) significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terbutaline was partly blocked by amiloride and ouabain, which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7%, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7% and 56.8%, respectively.Terbutaline can accelerate alveolar liquid clearance through increasing sodium transport to attenuate pulmonary edema, thus improving gas exchange, which may have therapeutical effect on pulmonary edema after acute lung injury.

Objective Elevated myocardial energy expenditure (MEE) is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF) are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. Methods A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG) pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. Results The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05). Conclusions These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients.

AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mm×5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group I served as untreated control group. Group II received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group III received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group III (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cm3, and 1.412±0.146 g, respectively) and group II (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P

To investigate the in vitro antitumor effect of adenovirus-mediated small interfering RNAs (siRNAs) on pancreatic cancer and the associated mechanism.A 63-nucleotide (nt) oligonucleotide encoding K-ras(val12) and specific siRNA were introduced into pSilencer 3.1-H1, then the H1-RNA promoter and siRNA coding insert were subcloned into pAdTrack to get plasmid pAdTrackH1-K-ras(val12). After homologous recombination in bacteria and transfections of such plasmids into a mammalian packaging cell line 293, siRNA expressing adenovirus AdH1-K-ras(val12) was obtained. Stable suppression of K-ras(val12) was detected by Northern blot and Western blot. Apoptosis in Panc-1 cells was detected by flow cytometry.We obtained adenovirus AdH1-K-ras(val12) carrying the pSilencer 3.1-H1 cassette, which could mediate gene silencing. Through siRNA targeted K-ras(val12), the oncogenic phenotype of cancer cells was reversed. Flow cytometry showed that apoptotic index of Panc-1 cells was significantly higher in the AdH1-K-ras(val12)-treatment group (18.70% at 72 h post-infection, 49.55% at 96 h post-infection) compared to the control groups (3.47%, 3.98% at 72 and 96 h post-infection of AdH1-empty, respectively; 4.21%, 3.78% at 72 and 96 h post-infection of AdH1-p53, respectively) (P0.05).These results demonstrate that adenoviral vectors can be used to mediate RNA interference (RNAi) to induce persistent loss of functional phenotypes. In gene therapy, the selective down-regulation of only the mutant version of a gene allows for highly specific effects on tumor cells, while leaving the normal cells untouched. In addition, the apoptosis of pancreatic cancer cell line Panc-1 can be induced after AdH1-K-ras(val12) infection. This kind of adenovirus based on RNAi might be a promising vector for cancer therapy.