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The complete curriculum schedule of the School of Dentistry, National Taiwan University (NTU) appeared in 1960. This study aimed to understand the development of dental education in Taiwan by comparing the past and current dental school curricula of NTU.This study collected the 1960, 1990 and 2020 dental school curriculum schedules for dental students of NTU from the related websites and used the documentary and secondary data analyses to further compare the obtained data.The number of credits for all the curricula offered by NTU to undergraduate dental students decreased from 264 in 1960 to 243 in 1990 and further to 242 in 2020 with a total decrease of 22 credits by 8.3%. The number (proportion) of credits of medicine courses decreased from 102 (38.6%) in 1960 to 52 (21.4%) in 1990, and then increased to 60 (24.8%) in 2020, with a total decrease of 42 credits by 41.2%, while those of dentistry courses increased from 70 (26.5%) in 1960 to 122 (50.2%) in 1990 and further to 132 (54.5%) in 2020, with a total increase of 62 credits by 88.6%. Among them, clinical practice of dentistry had the greatest growth with a total increase of 42 credits by 233.3%.The increase of dentistry courses and the decrease of medicine courses are the general trends for modern dental education. The dental school of NTU has the ability to provide more refined dentistry courses to catch the world trend of dental education.

Background: Traditional drug development takes a good deal of time and effort, computational drug repositioning enables to discover the underlying mechanisms of drugs, thereby reducing the cost of drug discovery and development. However, present methods merely consider structure-based drug-related network for feature extraction of drugs and diseases in the biological network. Results: In this paper, we develop a novel model, namely DRGDL, based on geometric deep learning and negative sample selection to infer potential drug-disease associations (DDAs), which can more comprehensively make use of the biological features of drugs and diseases. Specifically, the lower-order and higher-order representations of drugs and diseases are captured by two different geometric deep learning strategies, and then negative samples are constructed by a negative selection strategy. A machine learning classifier is applied to complete the prediction task of DDAs by integrating two representations of drugs and diseases. Experiment results demonstrate that DRGDL achieves excellent performance under ten-fold cross-validation on the benchmark dataset.

Adaptive trait divergence is usually episodic rather than universal in a phylogeny. To determine whether trait divergence reaches an extreme level (i.e. deviation from neutrality), the evolutionary rate of the species and intraspecific variation must be taken into account. Accordingly, we attempt to explore the trend of trait divergence over divergence times conditioned on the genetic distance. The Brownian motion (BM) model, a commonly used random-walk process for describing the neutral evolution of traits, is used to simulate the distribution of trait divergence under neutrality. The observed trait divergences are then compared to the BM expectations to detect outliers, which are considered to be selected. We assessed the ability of this method to characterize trait divergence under selection among 14 Lithocarpus species in Taiwan. The results are consistent with the previous inference of phylogenetic constraint based on tests of the phylogenetic signal, but further signals of adaptive and conserved trait divergences are detected between some lineages derived from particular nodes (common ancestors), indicating differential investments in growth rate and chemical defense among some endemic species in Taiwan. These results show that the adaptive divergence of environment-related traits is transient, episodic, and punctuated. Under strong selection pressure, the trait divergence after standard deviation correction will be more significant because the trait variance within the population decreases. However, it tends to be an overestimation of conservative evolution in older common ancestors due to the larger standard deviation produced from diverse descendants. Nevertheless, this study still provides a simple approach to detect adaptive divergence in a phylogenetic framework.

Purpose Early prediction of acute kidney injury (AKI) in septic patients is difficult. This study aimed to assess the values of renal resistive index (RI), central venous pressure (CVP), and their combination in the early prediction of sepsis-induced AKI. Methods A prospective cohort study was performed in septic patients. The variables potentially associated with AKI were recorded at admission and compared between the AKI and non-AKI groups. The variables independently associated with sepsis-induced AKI were identified using multivariable logistic regression, and the area under the receiver operating characteristic curve (AUROC) analysis was calculated. Results A total of 124 septic patients were included. Septic shock (OR, 3.28; P = 0.002), high CVP (OR, 1.92; P = 0.012) and renal RI (OR, 2.58; P = 0.009), low diastolic perfusion pressure (DPP) (OR, 2.15; P = 0.010) at admission were independent risk factors for sepsis-induced AKI. The AUROC value of the combination of RI and CVP was greater compared with either RI or CVP alone in predicting sepsis-induced AKI (AUROC = 0.858, 0.811, and 0.780, respectively). Conclusions The combination of RI and CVP was more valuable than either of the two parameters in the early prediction for sepsis-induced AKI.

Background: The axillary vein is an easily accessible vessel that can be used for ultrasound-guided central vascular access and offers an alternative to the internal jugular and subclavian veins. The objective of this study was to identify which transducer orientation, longitudinal or transverse, is better for imaging the axillary vein with ultrasound. Methods: We analyzed 236 patients who had undergone central venous cannulation of axillary vein in this retrospective study. Patients were divided into two groups, the longitudinal approach group (n=120) and transverse approach group (n=116). Recorded the one-attempt success rate, operation time, arterial puncture rate and pneumothorax rate. We perform chest radiography to confirm pneumothorax on all patients. We compared the one-attempt success rate, operation time, arterial puncture rate and pneumothorax rate between the two groups. Results: The two groups were comparable with clinical characters of patients. The overall success rates of the longitudinal group and the transverse group were both 100%. The rate of one-attempt success in the longitudinal approach group is higher than the transverse approach group (91.7% vs. 82.8%, P=0.040). The transverse approach group had shorter operation time than the longitudinal group (184.7±8.1 vs. 287.5±19.6 seconds, P=0.000). The two groups had lower postoperative complications. Arterial puncture occurred in 1 of 120 longitudinal and 2 of 116 transverse attempts and this difference was no significant (P=0.541). No pneumothorax occurred in the two groups. Conclusions: The longitudinal approach during ultrasound-guided axillary vein cannulation is associated with greater one-attempt success rate compared with the transverse approach by experienced operators. The transverse approach has shorter operation time. The two groups have lower postoperative complications and are comparable with pneumothorax and arterial puncture.

// Long-Zi Liu 1, * , Yi-Zhou He 2, * , Ping-Ping Dong 3, * , Li-Jie Ma 1 , Zhi-Chao Wang 1 , Xin-Yang Liu 4 , Meng Duan 1 , Liu-Xiao Yang 1 , Jie-Yi Shi 1 , Jian Zhou 1 , Jia Fan 1 , Qiang Gao 1 , Xiao-Ying Wang 1 1 Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, P. R. China 2 Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R, China 3 Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, Shanghai 200032, P. R. China 4 Department of Medical Oncology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China * These authors have contributed equally to this work Correspondence to: Qiang Gao, email: gaoqiang@fudan.edu.cn Xiao-Ying Wang, email: wang.xiaoying1@zs-hospital.sh.cn Keywords: PTP4A1, intrahepatic cholangiocarcinoma, prognosis, oncogene, epithelial-mesenchymal transition Received: February 19, 2016 Accepted: September 02, 2016 Published: September 19, 2016 ABSTRACT The protein tyrosine phosphatase PTP4A1 is a key molecule that activates tyrosine phosphorylation, which is important for cancer progression and metastasis. However, the clinical implications and biological function of PTP4A1 in intrahepatic cholangiocarcinoma (ICC) remains unknown. Here, we showed that PTP4A1 was frequently overexpressed in ICC versus adjacent non-tumor tissues. This overexpression significantly correlated with aggressive tumor characteristics like the presence of lymph node metastasis and advanced tumor stages. Survival analysis further indicated that high PTP4A1 expression was significantly and independently associated with worse survival and increased recurrence in ICC patients. Moreover, through forced overexpression and knock-down of PTPT4A1, we demonstrated that PTP4A1 could significantly promote ICC cells proliferation, colony formation, migration, and invasion in vitro , and markedly enhance tumor progression in vivo . Mechanistically, PTP4A1 was involved in PI3K/AKT signaling and its downstream molecules, such as phosphorylation level of GSK3β and up-regulation of CyclinD1, in ICC cells to promote proliferation. Importantly, PTP4A1 induced ICC cells invasion was through activating PI3K/AKT signaling controlled epithelial-mesenchymal transition (EMT) process by up-regulating Zeb1 and Snail. Thus, PTP4A1 may serve as a potential oncogene that was a valuable prognostic biomarker and therapeutic target for ICC.

The ubiquitin-dependent proteasomal degradation of proteins controls signaling and cellular survival. In this study, we found that ubiquitin associated protein 2 (UBAP2) was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues. Furthermore, higher expression of UBAP2 in cancer tissues was correlated with good prognosis in HCC patients. Knockdown of UBAP2 significantly enhanced the invasion and proliferation of HCC cells in vitro and promoted tumor growth in vivo, while enforced expression of UBAP2 impaired the aggressive ability and tumor growth of HCC cells. Mechanistically, UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination, and then inhibited HCC progression. Collectively, UBAP2 appears as a novel marker for predicting prognosis and a therapeutic target for HCC.

It's difficult to diagnose gastroesophageal anastomotic leakage (GAL) at early postoperative stage. This study was conducted to evaluate the early predictive value of plasma cytokines levels on GAL in patients undergoing esophagectomy.Consecutive esophageal cancer patients who underwent esophagectomy and admitted to Surgical Intensive Care Unit (SICU) just after surgery were retrospectively analyzed. The baseline and postoperative 1 day plasma cytokine levels were collected and analyzed to evaluate the predictive value for clinically important anastomotic leakage. Area under receiver operating characteristic curve (AUROC) analysis was also performed.A total of 183 patients were included. Sixteen patients (8.74%) experienced GAL (GAL group) and the others did not (non-GAL group). The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2R, IL-6, IL-8 and IL-10 in plasma on the first postoperative day significantly increased in the GAL group than in the non-GAL group (P0.05). IL-6, IL-8 and IL-10 were fair predictors of GAL (AUROC0.7) and the other two cytokines were poorly predictive (AUROC0.7). The mean length of ICU and hospital stay were significantly longer in the GAL group than in the non-GAL group (P0.05).Plasma concentrations of IL-6, IL-8 and IL-10 on the first postoperative day can predict clinically important GAL in patients undergoing esophagectomy.

Focus on solving the life and reliability problems of long-life and high reliability products, a method of modeling and parameter estimation on reliability evaluation and life prediction with accelerated degradation data was proposed in this paper. In the first, three statistical methods of degradation test were analyzed, then according to the features of accelerated degradation data, the statistical model of degradation data based on pseudo-life was established. This method can effectively utilize the horizontal information of degradation data of product under different accelerated stress level, and integrate the advantage that continuous-time function model fits the degradation curve of product strongly, and improve the accuracy of reliability assessment and life prediction of product.

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

The object of the statistical analysis is the statistical information. To correctly identify the type of statistical information is the most important prerequisite for rational use of statistical analysis methods. In this paper, the common methods for normality test are introduced theoretically. And the figure test and partial kurtosis test of normal distribution are proposed with detailed testing steps, suitable situation and mathematical model. It is demonstrated by simulation that both have good test results and practical value.

In order to solve the key technology and method in reliability study of the long-life products, the analysis method of degradation data based on the degradation amount distribution was proposed in this paper. On the basis of statistical model, by analyzing three models of degradation amount distribution, it can be got there is a large number of reliability information with high-reliable and long-life products in performance degradation data. In the case of not getting the failure data by life test and accelerated life test, reliability assessment and life prediction could be carried out for high reliability and long life products with performance degradation data.

In order to solve the key technology and method in reliability study of the long-life products, the analysis method of degradation data based on the degradation amount distribution was proposed in this paper. On the basis of statistical model, by analyzing three models of degradation amount distribution, it can be got there is a large number of reliability information with high-reliable and long-life products in performance degradation data. In the case of not getting the failure data by life test and accelerated life test, reliability assessment and life prediction could be carried out for high reliability and long life products with performance degradation data.

In order to solve the reliability assessment in the case of competition failure induced by the coexistence between burst-type failure and degradation-type failure in the product, the method of degradation amount distribution was adopted to describe the degradation process of performance in product. Considering the relativity between sudden failure and degradation degree, the cumulative distribution function of sudden failure was calculated from the standpoint of degradation amount. Eliminating the affect of sudden failure according to a certain conditional probability in the degradation amount distribution function, which helps to realize reliability assessment based on competitive failure analysis.

A new procedure of learning in Gaussian graphical models is proposed under the assumption that samples are possibly dependent. This assumption, which is pragmatically applied in various areas of multivariate analysis ranging from bioinformatics to finance, makes standard Gaussian graphical models (GGMs) unsuitable. We demonstrate that the advantage of modeling dependence among samples is that the true discovery rate and positive predictive value are improved substantially than if standard GGMs are applied and the dependence among samples is ignored. The new method, called matrix-variate Gaussian graphical models (MGGMs), involves simultaneously modeling variable and sample dependencies with the matrix-normal distribution. The computation is carried out using a Markov chain Monte Carlo (MCMC) sampling scheme for graphical model determination and parameter estimation. Simulation studies and two real-world examples in biology and finance further illustrate the benefits of the new models.

Purpose: Cytokeratin 10 (CK10) was found to be expressed differently in human hepatocellular carcinoma (HCC) cell lines with different metastatic potentials in our previous research. The aim of this study was to assess the value of CK10 alone or in combination with cytokeratin 19 (CK19) in predicting tumor recurrence after curative resection in HCC patients. Experimental Design: CK10 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated using immunofluorescence assay, quantitative real-time reverse transcription-PCR, and Western blot analyses. Tumor tissue microarrays of 300 HCC patients who underwent curative resection between 1997 and 2000 were used to detect the expressions of CK10 and CK19. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CK10 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Both univariate and multivariate analyses revealed that CK10 was a significant predictor for overall survival (OS) and disease-free survival, and that CK19 was a significant predictor for OS. CK10 expression was correlated with poor prognosis regardless of α-fetoprotein, tumor-node-metastasis stage, and vascular invasion. The 7-year OS and disease-free survival rates in CK10+ and/or CK19+ patients were 30.0% and 37.6%, respectively, which were significantly lower than that of CK10−/CK19− patients (56.1% and 60.0%, respectively; P < 0.001). Conclusion: CK10 is associated with HCC invasiveness. CK10 alone, or in combination with CK19, can be a novel predictor for poor prognosis of HCC patients after curative resection.

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

Introduction The relationship between admission time and intensive care unit (ICU) mortality is inconclusive and influenced by various factors. This study aims to estimate the effect of admission time on ICU outcomes in a tertiary teaching hospital in China by propensity score matching (PSM) and stratified analysis. Methods A total of 2,891 consecutive patients were enrolled in this study from 1 January 2009 to 29 December 2011. Multivariate logistic regression and survival analysis were performed in this retrospective study. PSM and stratified analysis were applied for confounding factors, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score and admission types. Results Compared with office hour subgroup (n = 2,716), nighttime (NT, n = 175) subgroup had higher APACHE II scores (14 vs. 8, P

The prognostic power of n-terminal pro-brain natriuretic peptide (NT-proBNP) in sepsis is disputable and unstable among different models. We attempt to evaluate the prognostic potential of NT-proBNP in combination with the sequential organ failure assessment (SOFA) score in sepsis.In this retrospective study, 100 consecutive sepsis patients were enrolled. Clinical data such as admission SOFA, the Acute Physiologic and Chronic Health Evaluation score, shock prevalence, use of lung protective ventilation, vasopressors, and glucocorticoids were recorded. Additionally, serum creatinine (Scr1 and Scr3) and NT-proBNP (NT-proBNP1 and NT-proBNP3) were assayed and evaluated at admission and on day 3 respectively.DNT-proBNP (NT-proBNP3 minus NT-proBNP1) (P0.001, Hazard ratio (HR) = 1.245, 95% confidence interval (CI), 1.137 - 1.362) and admission SOFA (P0.001, HR = 1.197, 95%CI, 1.106 - 1.295) were independently related to in-hospital mortality. Their combination was a more robust predictor for in-hospital mortality than either of them individually. Patients with high DNT-proBNP and SOFA had the poorest prognosis.In our study, both DNT-proBNP and SOFA were independent predictors of septic patients' prognosis. Moreover, the combination of DNT-proBNP and admission SOFA provided a novel strategy that contained information regarding both the response to treatment and sepsis severity.

To identify the side population (SP) cells from four hepatocellular carcinoma (HCC) cell lines with stepwise metastatic potentials.SP cells were sorted from HCCLM3, MHCC97-H, MHCC97-L and Hep3B by flow cytometry, and then analyzed by differentiation study, clonogenic assay, chemoresistance study and tumorigenicity assay in vivo. The expression of ABCG(2) in SP cells was detected by immunocytochemistry, western blotting and real-time quantitative PCR, respectively.There was significant difference in SP proportion among HCCLM3, MHCC97-H, MHCC97-L and Hep3B (28.7 +/- 1.6%, 14.5 +/- 0.6%, 4.2 +/- 0.4%, 0.9 +/- 0.1%, respectively, P0.01). All the SP cells showed similar characteristics of self-renewal, high clonogenicity, remarkable chemo-resistance and high expression of ABCG(2). As low as 2,000 SP cells could initiate tumors in non-obese diabetic/severe combined immunodeficiency mice successfully.SP cells purified from HCC cell lines harbors cancer stem cell-like properties, and may be related to the metastatic potentials and therapeutic-resistance of HCC.