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1.  Characteristics and viral propagation properties of a new human diploid cell line, walvax-2, and its suitability as a candidate cell substrate for vaccine production 
Human Vaccines & Immunotherapeutics  2015;11(4):998-1009.
Human diploid cell strains (HDCSs), possessing identical chromosome sets known to be free of all known adventitious agents, are of great use in developing human vaccines. However it is extremely difficult to obtain qualified HDCSs that can satisfy the requirements for the mass production of vaccines. We have developed a new HDCS, Walvax-2, which we derived from the lung tissue of a 3-month-old fetus. We established primary, master and working cell banks successfully from reconstituted frozen cells. Observations during the concurrent propagation of Walvax-2 and MRC-5 cells revealed differences in terms of growth rate, cell viability and viral sensitivities. Specifically, Walvax-2 cells replicated more rapidly than MRC-5 cells, with Walvax-2 cells attaining the same degree of confluence in 48 hours as was reached by MRC-5 cells in 72 hours. Moreover, Walvax-2 cells attained 58 passages of cell doublings whereas MRC-5 reached 48 passages during this period. We also assessed the susceptibility of these cells to rabies, hepatitis A, and Varicella viruses. Analysis of virus titers showed the Walvax-2 cells to be equal or superior to MRC-5 cells for cultivating these viruses. Furthermore, in order to characterize the Walvax-2 cell banks, a series of tests including cell identification, chromosomal characterization, tumorigenicity, as well as tests for the presence of microbial agents, exogenous viruses, and retroviruses, were conducted according to standard international protocols. In conclusion, results from this study show that Walvax-2 cell banks are a promising cell substrate and could potentially be used for the manufacturing of HDCVs.
doi:10.1080/21645515.2015.1009811
PMCID: PMC4526020  PMID: 25803132
biological characteristics; cell substrate; human diploid cell strain (HDCSs); human diploid cell vaccines (HDCVs); viral sensitivities
2.  Comparison of Support-Vector Machine and Sparse Representation Using a Modified Rule-Based Method for Automated Myocardial Ischemia Detection 
An automatic method is presented for detecting myocardial ischemia, which can be considered as the early symptom of acute coronary events. Myocardial ischemia commonly manifests as ST- and T-wave changes on ECG signals. The methods in this study are proposed to detect abnormal ECG beats using knowledge-based features and classification methods. A novel classification method, sparse representation-based classification (SRC), is involved to improve the performance of the existing algorithms. A comparison was made between two classification methods, SRC and support-vector machine (SVM), using rule-based vectors as input feature space. The two methods are proposed with quantitative evaluation to validate their performances. The results of SRC method encompassed with rule-based features demonstrate higher sensitivity than that of SVM. However, the specificity and precision are a trade-off. Moreover, SRC method is less dependent on the selection of rule-based features and can achieve high performance using fewer features. The overall performances of the two methods proposed in this study are better than the previous methods.
doi:10.1155/2016/9460375
PMCID: PMC4746342  PMID: 26925158
3.  Regime for Bowel Preparation in Patients Scheduled to Colonoscopy: Low-Residue Diet or Clear Liquid Diet? Evidence From Systematic Review With Power Analysis 
Medicine  2016;95(1):e2432.
Supplemental Digital Content is available in the text
Abstract
Clear liquid diet (CLD) is used to perform bowel preparation before colonoscopy traditionally, but several clinical studies indicated that low-residue diet (LRD) generates equal effects to CLD and a conclusive conclusion has not yet been yielded. The systematic review was performed to address this conflict and facilitate informed decision-making eventually.
To capture randomized controlled trials (RCTs) comparing LRD with CLD in terms of bowel preparation, a search was performed in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Science Direct, recent conference abstracts, Google Scholar, and Clinicaltrials.gov through May 2015. We performed all meta-analyses based on fixed- or random-effects model, which is generated from clinical characteristics and methodology. Moreover, the G∗Power software was adopted to achieve statistical power for each outcome.
In total, we captured 109 potential citations at initial search stage and 2 topic-related articles were included through other sources. After critical appraisal, 7 RCTs were eligible for our inclusion criteria. Meta-analyses generated similar effects in bowel preparation quality, efficacy of colon cleansing, and compliance with recommended dietary regime when LRD versus CLD regime, but patients who were prescribed to receive LRD have slightly better tolerance (RR, 1.06; 95% CI, 1.02–1.11) and tended to repeat the same preparation regime in future (RR, 1.17; 95% CI, 1.09–1.26) relative to patients in CLD. Importantly, both regimes resulted in similar adverse events (AEs).
With the best available evidence, LRD could be recommended to be as standard regime for bowel preparation prior to colonoscopy.
doi:10.1097/MD.0000000000002432
PMCID: PMC4706267  PMID: 26735547
4.  Large-diameter compression arteries as a possible facilitating factor for trigeminal neuralgia: analysis of axial and radial diffusivity 
Acta Neurochirurgica  2016;158:521-526.
Background
Neurovascular compression (NVC) of the trigeminal nerve is associated with trigeminal neuralgia (TN). Some arteries that compress the trigeminal nerve are large, while others are small. This study evaluated the influence of diameter of compression arteries (DCA) on NVC with and without TN using axial diffusivity (AD) and radial diffusivity (RD) of magnetic resonance (MR) imaging.
Methods
Fifty TN patients with unilateral NVC, 50 asymptomatic patients with unilateral NVC, and 50 healthy controls (HC) were divided into three groups (NVC with TN, NVC without TN, and HC). The three groups were imaged with a 3.0-T MR system using three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) and diffusion tensor imaging (DTI). We compared the mean size of DCA between NVC with and without TN. The mean values of AD and RD at the site of NVC were compared between the three groups. Correlation analyses were performed between the DCA and the diffusion metrics (AD and RD) in NVC patients with and without TN.
Results
The mean DCA in NVC patients with TN (1.58 ± 0.34 mm) was larger than that without TN (0.89 ± 0.29 mm). Compared with NVC without TN and HC, the mean values of RD at the site of NVC with TN were significantly increased; however, no significant changes of AD were found between the groups. Correlation analysis showed that DCA positively correlated with RD in NVC patients with and without TN (r = 0.830, p = 0.000). No significant correlation was found between DCA and AD (r = 0.178, p = 0.077).
Conclusions
Larger-diameter compression arteries may increase the chances of TN, and may be a possible facilitating factor for TN.
doi:10.1007/s00701-015-2673-4
PMCID: PMC4752583  PMID: 26733127
Axial diffusivity; Demyelination; Neurovascular compression; Radial diffusivity; Trigeminal neuralgia
6.  Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice 
Scientific Reports  2015;5:16024.
Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus.
doi:10.1038/srep16024
PMCID: PMC4629199  PMID: 26522512
7.  Between the Living and the Dead: Trauma Medicine and Forensic Medicine in the Mid-Qing 
Frontiers of history in China  2015;10(1):38-73.
This paper analyzes the influence of forensic medicine on therapeutic medicine through a case study of Qian Xiuchang and Hu Tingguang, two Chinese doctors who specialized in treating traumatic injuries. During the early nineteenth century, both men compiled medical treatises that sought to improve on a scholarly model of “rectifying bones” articulated in 1742 by the Imperially-Compiled Golden Mirror of the Medical Lineage. Both texts also incorporated information from forensic medicine, including official inquest diagrams and checklists promulgated by the Qing government. I show that they drew on these forensic materials to help address two interlinked medical issues: understanding the effects of injury on different parts of the body, and clarifying the location and form of the body’s bones. Overall, I suggest that the exchange of ideas between the realm of therapeutic medicine and forensic medicine was an important epistemological strategy that doctors and officials alike employed to improve their knowledge of the material body.
doi:10.3868/s020-004-015-0002-0
PMCID: PMC4620851  PMID: 26512255
forensics; trauma medicine; Qing medicine; bone-setting; Qian Xiuchang; Hu Tingguang; Yuzuan Yizong jinjian; Xi yuan jilu
8.  PALB2 mutations in breast cancer patients from a multi-ethnic region in northwest China 
Background
Germline mutations in PALB2 gene make a small contribution to heritable breast cancer susceptibility. A recent report has revealed that women with mutations in the PALB2 gene were more than nine times as likely to develop breast cancer compared to those without. The aim of this study is to understand the status of PALB2 mutations among Chinese high-risk breast cancer patients in a multi-ethnic region in China.
Methods
152 patients with hereditary predisposition to breast cancer from the Xinjing region of China were enrolled in the study, and 100 control samples from healthy women were collected in the same locality. We sequenced the coding sequences and flanking intronic regions of PALB2 gene from DNA samples obtained from all subjects by direct sequencing.
Results
A total of 4 deleterious PALB2 mutations were identified in 152 breast cancer patients with a prevalence of about 2.6 % (4/152). The PALB2 mutation prevalence was 3.2 % (3/95) in cases with family history of breast cancer. In addition to the four deleterious mutations, we identified nine missense variants in 12 patients, using the prediction Softwares SIFT and PolyPhen, four of which might be disease associated (in 5 patients). Two of the 4 patients with deleterious mutations and 2 of the 5 patients presenting putative deleterious missense mutations had triple-negative breast cancer. No PALB2 mutation carriers were identified in 100 healthy controls.
Conclusion
PALB2 mutations account for a small, but not negligible, proportion of patients with hereditary predisposition to breast cancer in the Xinjing region of China.
doi:10.1186/s40001-015-0182-9
PMCID: PMC4618884  PMID: 26489409
PALB2; Breast cancer; Genetic testing; Mutation
9.  Crystal Structure and Identification of Two Key Amino Acids Involved in AI-2 Production and Biofilm Formation in Streptococcus suis LuxS 
PLoS ONE  2015;10(10):e0138826.
Streptococcus suis has emerged as an important zoonotic pathogen that causes meningitis, arthritis, septicemia and even sudden death in pigs and humans. Quorum sensing is the signaling network for cell-to-cell communication that bacterial cells can use to monitor their own population density through production and exchange of signal molecules. S-Ribosylhomocysteinase (LuxS) is the key enzyme involved in the activated methyl cycle. Autoinducer 2 (AI-2) is the adduct of borate and a ribose derivative and is produced from S-adenosylhomocysteine (SAH). AI-2 can mediate interspecies communication and in some species facilitate the bacterial behavior regulation such as biofilm formation and virulence in both Gram-positive and Gram-negative bacteria. Here, we reported the overexpression, purification and crystallographic structure of LuxS from S. suis. Our results showed the catalytically active LuxS exists as a homodimer in solution. Inductively coupled plasma-mass spectrometry (ICP-MS) revealed the presence of Zn2+ in LuxS. Although the core structure shares the similar topology with LuxS proteins from other bacterial species, structural analyses and comparative amino acid sequence alignments identified two key amino acid differences in S. suis LuxS, Phe80 and His87, which are located near the substrate binding site. The results of site-directed mutagenesis and enzymology studies confirmed that these two residues affect the catalytic activity of the enzyme. These in vitro results were corroborated in vivo by expression of the LuxS variants in a S. suis ΔluxS strain. The single and two amino acid of LuxS variant decreased AI-2 production and biofilm formation significantly compared to that of the parent strain. Our findings highlight the importance of key LuxS residues that influence the AI-2 production and biofilm formation in S.suis.
doi:10.1371/journal.pone.0138826
PMCID: PMC4618692  PMID: 26484864
10.  Dynamic identifying protein functional modules based on adaptive density modularity in protein-protein interaction networks 
BMC Bioinformatics  2015;16(Suppl 12):S5.
Background
The identification of protein functional modules would be a great aid in furthering our knowledge of the principles of cellular organization. Most existing algorithms for identifying protein functional modules have a common defect -- once a protein node is assigned to a functional module, there is no chance to move the protein to the other functional modules during the follow-up processes, which lead the erroneous partitioning occurred at previous step to accumulate till to the end.
Results
In this paper, we design a new algorithm ADM (Adaptive Density Modularity) to detect protein functional modules based on adaptive density modularity. In ADM algorithm, according to the comparison between external closely associated degree and internal closely associated degree, the partitioning of a protein-protein interaction network into functional modules always evolves quickly to increase the density modularity of the network. The integration of density modularity into the new algorithm not only overcomes the drawback mentioned above, but also contributes to identifying protein functional modules more effectively.
Conclusions
The experimental result reveals that the performance of ADM algorithm is superior to many state-of-the-art protein functional modules detection techniques in aspect of the accuracy of prediction. Moreover, the identified protein functional modules are statistically significant in terms of "Biological Process" annotated in Gene Ontology, which provides substantial support for revealing the principles of cellular organization.
doi:10.1186/1471-2105-16-S12-S5
PMCID: PMC4705501  PMID: 26330105
adaptive density modularity; internal closely associated degree; external closely associated degree; protein functional modules
11.  Role of Enteral Immunonutrition in Patients Undergoing Surgery for Gastric Cancer 
Medicine  2015;94(31):e1311.
Supplemental Digital Content is available in the text
Abstract
Gastric cancer (GC) is one of the most common upper gastrointestinal malignancies. Surgical resection remains the mainstay of curative treatment for GC. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve inflammatory response of patients undergoing surgery for GC; however, conclusions across studies still remain unclear. We aimed to evaluate the effects of EIN for such patients.
We searched some electronic databases including PubMed, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE to identify any latent studies which investigated the effects of EIN compared with standard EN on GC patients who undergoing surgery until the end of December 30, 2014. Relative risk (RR), mean difference (MD), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated and we also assessed heterogeneity by using Cochrane Q and I2 statistic combined with corresponding P-value.
We included 9 eligible studies which included 785 patients eventually. The meta-analysis results shown that EIN increased level of IgA (MD, 0.31; 95% CI, 0.12–0.51), IgG (MD, 1.5; 95% CI, 0.73–2.28), IgM (MD, 0.22; 95% CI, 0.06–0.39), CD4+ (SMD, 0.81; 95% CI, 0.53–1.09), CD3+ (SMD, 0.68; 95% CI, 0.21–1.15), CD4+/CD8+ ratio (MD, 0.56; 95% CI, 0.12–1.01), and NK cell (MD, 2.35; 95% CI, 0.66–4.05); decreased IL-6 (MD, −98.22; 95% CI, −156.16 to −40.28) and TNF-α (MD, −118.29; 95% CI, −162.00 to −74.58), but not improve remained outcomes of interest involving postoperative complications, length of hospitalization, serum total protein, and CD8+. Descriptive analysis suggested that EIN also increased the concentration of IL-2 but not CRP. Impact on lymphocytes remains inconsistent.
EIN is effective for enhancing host immunity and relieving the inflammatory response in GC patients undergoing gastrectomy, but clinical outcomes cannot be benefit from it. Heterogeneity caused by different compositions and timing of administration of EIN regimes and not enough sample size and number of eligible studies in most of sensitive analyses with subgroup analysis may impaired the power of our study, and thus some large-scale and well-designed studies are warranted to further establish effects.
doi:10.1097/MD.0000000000001311
PMCID: PMC4616579  PMID: 26252314
12.  Oral Motor Intervention Improved the Oral Feeding in Preterm Infants 
Medicine  2015;94(31):e1310.
Supplemental Digital Content is available in the text
Abstract
Oral feeding for preterm infants has been a thorny problem worldwide. To improve the efficacy of oral feeding in preterm infants, oral motor intervention (OMI), which consists of nonnutritive sucking, oral stimulation, and oral support, was developed. Published studies demonstrated that OMI may be as an alternative treatment to solve this problem; however, these results remain controversial. We conducted a meta-analysis with trial sequential analysis (TSA) to objectively evaluate the potential of OMI for improving the current status of oral feeding in preterm infants.
A search of PubMed, EMBASE, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed to capture relevant citations until at the end of October, 2014. Lists of references of eligible studies and reviews were also hand-checked to include any latent studies. Two independent investigators screened literature, extracted data, and assessed the methodology, and then a meta-analysis and TSA was performed by using Reviewer Manager (RevMan) 5.3 and TSA 0.9 beta, respectively.
A total of 11 randomized controlled trials (RCTs), which included 855 participants, were incorporated into our meta-analysis. The meta-analyses suggested that OMI is associated with the reduced transition time (ie, the time needed from tube feeding to totally oral feeding) (mean difference [MD], −4.03; 95% confidence interval [CI], −5.22 to −2.84), shorten hospital stays (MD, −3.64; 95% CI, −5.57 to −1.71), increased feeding efficiency (MD, 0.08; 95% CI, 0.36–1.27), and intake of milk (MD, 0.14; 95% CI, 0.06–0.21) rather than weight gain. Results of TSA for each outcomes of interest confirmed these pooled results.
With present evidences, OMI can be as an alternative to improve the condition of transition time, length of hospital stays, feeding efficiency, and intake of milk in preterm infants. However, the pooled results may be impaired due to low quality included, and thus, well-designed and large RCTs were needed to further established effects.
doi:10.1097/MD.0000000000001310
PMCID: PMC4616601  PMID: 26252313
13.  High-level expression of human arginase I in Pichia pastoris and its immobilization on chitosan to produce L-ornithine 
BMC Biotechnology  2015;15:66.
Background
L-ornithine (L-Orn), is an intermediate metabolite in the urea cycle that plays a significant role in humans. L-Orn can be obtained from the catalysis of L-arginine (L-Arg) by arginase. The Pichia pastoris expression system offers the possibility of generating a large amount of recombinant protein. The immobilized enzyme technology can overcome the difficulties in recovery, recycling and long-term stability that result from the use of free enzyme.
Methods
The recombinant human arginase I (ARG I) was obtained using an optimized method with the Pichia pastoris GS115 as the host strain. Chitosan paticles were cross-linked with glutaraldehyde and rinsed exhaustively. Then the expressed ARG I was immobilized on the crosslinked chitosan particles, and the enzymatic properties of both the free and immobilized enzymes were evaluated. At last, the immobilized ARG I was employed to catalyze L-Arg to L-Orn.
Results
The results indicated that these two states both exhibited optimal activity under the same condition of pH10 at 40 °C. However, the immobilized ARG I exhibited the remarkable thermal and long-term stability as well as broad adaptability to pH, suggesting its potential for wide application in future industry. After a careful analysis of its catalytic conditions, immobilized ARG I was employed to catalyze the conversion of L-Arg to L-Orn under optimal condition of 1 % glutaraldehyde, 1 mM Mn2+, 40 °C, pH10 and an L-arginine (L-Arg) concentration of 200 g/L, achieving a highly converted content of 149.g/L L-Orn.
Conclusions
In this work, ARG Ι was abundantly expressed, and an efficient, facile and repeatable method was developed to synthesize high-quality L-Orn. This method not only solved the problem of obtaining a large amount of arginase, but also provided a promising alternative for the future industrial production of L-Orn.
doi:10.1186/s12896-015-0184-2
PMCID: PMC4521451  PMID: 26227111
L-ornithine; Recombinant human arginase I; Immobilization; Chitosan; L-arginine; Transformation
14.  Long-term results of a randomized phase III trial of TPF induction chemotherapy followed by surgery and radiation in locally advanced oral squamous cell carcinoma 
Oncotarget  2015;6(21):18707-18714.
Previously, we conducted a randomized phase III trial of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in surgically managed locally advanced oral squamous cell carcinoma (OSCC) and found no improvement in overall survival. This study reports long-term follow-up results from our initial trial. All patients had clinical stage III or IVA locally advanced OSCC. In the experimental group, patients received two cycles of TPF induction chemotherapy (75mg/m2 docetaxel d1, 75mg/m2 cisplatin d1, and 750mg/m2/day 5-fluorouracil d1-5) followed by radical surgery and post-operative radiotherapy; in the control group, patients received upfront radical surgery and post-operative radiotherapy. The primary endpoint was overall survival. Among 256 enrolled patients with a median follow-up of 70 months, estimated 5-year overall survival, disease-free survival, locoregional recurrence-free survival, and distant metastasis-free survival rates were 61.1%, 52.7%, 55.2%, and 60.4%, respectively. There were no significant differences in survival rates between experimental and control groups. However, patients with favorable pathologic responses had improved outcomes compared to those with unfavorable pathologic responses and to those in the control group. Although TPF induction chemotherapy did not improve long-term survival compared to surgery upfront in patients with stage III and IVA OSCC, a favorable pathologic response after induction chemotherapy may be used as a major endpoint and prognosticator in future studies. Furthermore, the negative results observed in this trial may be represent type II error from an underpowered study. Future larger scale phase III trials are warranted to investigate whether a significant benefit exists for TPF induction chemotherapy in surgically managed OSCC.
PMCID: PMC4621922  PMID: 26124084
induction chemotherapy; oral squamous cell carcinoma; cisplatin; docetaxel; 5-fluorouracil
15.  Immunonutrition Support for Patients Undergoing Surgery for Gastrointestinal Malignancy: Preoperative, Postoperative, or Perioperative? A Bayesian Network Meta-Analysis of Randomized Controlled Trials 
Medicine  2015;94(29):e1225.
Supplemental Digital Content is available in the text
Abstract
Enteral immunonutrition (EIN) has been established to be as a significantly important modality to prevent the postoperative infectious and noninfectious complications, enhance the immunity of host, and eventually improve the prognosis of gastrointestinal (GI) cancer patients undergoing surgery. However, different support routes, which are the optimum option, remain unclear. To evaluate the effects of different EIN support regimes for patients who underwent selective surgery for resectable GI malignancy, a Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) was conducted.
A search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was electronically searched until the end of December 2014. Moreover, we manually checked reference lists of eligible trials and review and retrieval unpublished literature. RCTs which investigated the comparative effects of EIN versus standard enteral nutrition (EN) or different EIN regimes were included if the clinical outcomes information can be extracted from it.
A total of 27 RCTs were incorporated into this study. Pair-wise meta-analyses suggested that preoperative (relative risk [RR], 0.58; 95% confidence interval [CI], 0.43–0.78), postoperative (RR, 0.63; 95% CI, 0.52–0.76), and perioperative EIN methods (RR, 0.46; 95% CI, 0.34–0.62) reduced incidence of postoperative infectious complications compared with standard EN. Moreover, perioperative EIN (RR, 0.65; 95% CI, 0.44–0.95) reduced the incidence of postoperative noninfectious complications, and the postoperative (mean difference [MD], −2.38; 95% CI, −3.4 to −1.31) and perioperative EIN (MD, −2.64; 95% CI, −3.28 to −1.99) also shortened the length of postoperative hospitalization compared with standard EN. NMA found that EIN support effectively improved the clinical outcomes of patients who underwent selective surgery for GI cancer compared with standard EN.
Our results suggest EIN support is promising alternative for operation management in comparison with standard EN, and perioperative EIN regime is the optimum option for managing clinical status of patients who underwent selective surgery for GI cancer.
doi:10.1097/MD.0000000000001225
PMCID: PMC4602990  PMID: 26200648
16.  Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis 
Medicine  2015;94(26):e1052.
Abstract
Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis.
Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out.
A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55–2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51–3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02–0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone.
With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD relative to ECT alone.
doi:10.1097/MD.0000000000001052
PMCID: PMC4504538  PMID: 26131818
17.  Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis 
Medicine  2015;94(26):e1052.
Abstract
Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis.
Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out.
A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55–2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51–3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02–0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone.
With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD relative to ECT alone.
doi:10.1097/MD.0000000000001052
PMCID: PMC4504538  PMID: 26131818
18.  Spinal hemangioblastoma combined with pilocytic astrocytoma 
Neurosciences  2015;20(3):280-284.
The combination of vascular anomalies with gliomas is rarely seen in the CNS, and is defined as ‘angioglioma’. However, the definition, category, and histopathogenesis of angiogliomas remain controversial. Here, we present an unusual case of spinal hemangioblastoma (HB) combined with pilocytic astrocytoma (PA). Spinal MRI revealed lesions extending from T9 to T12 segments, in a “sandwich-like” fashion. After resection of the tumor, histopathologic study confirmed the diagnosis of HB as well as PA. A comprehensive review of the literature was further conducted. We describe a case of spinal HB combined with PA, in addition we discuss the clinicopathological relationship between HB and PA under these conditions, which may facilitate the understanding of the histogenesis of an angioglioma and guide its diagnosis and treatment.
doi:10.17712/nsj.2015.3.20140225
PMCID: PMC4710347  PMID: 26166599
19.  Hepatoma-derived growth factor/nucleolin axis as a novel oncogenic pathway in liver carcinogenesis 
Oncotarget  2015;6(18):16253-16270.
Hepatoma-derived growth factor (HDGF) overexpression is involved in liver fibrosis and carcinogenesis. However, the receptor(s) and signaling for HDGF remain unclear. By using affinity chromatography and proteomic techniques, nucleolin (NCL) was identified and validated as a HDGF-interacting membrane protein in hepatoma cells. Exogenous HDGF elicited the membrane NCL accumulation within 0.5 hour by protein stabilization and transcriptional NCL upregulation within 24 hours. Blockade of surface NCL by antibodies neutralization potently suppressed HDGF uptake and HDGF-stimulated phosphatidylinositol 3-kinase (PI3K)/Akt signaling in hepatoma cells. By using rescectd hepatocellular carcinoma (HCC) tissues, immunohistochemical analysis revealed NCL overexpression was correlated with tumour grades, vascular invasion, serum alpha-fetoprotein levels and the poor survival in HCC patients. Multivariate analysis showed NCL was an independent prognostic factor for survival outcome of HCC patients after surgery. To delineate the role of NCL in liver carcinogenesis, ectopic NCL overexpression promoted the oncogenic behaviours and induced PI3K/Akt activation in hepatoma cells. Conversely, NCL knockdown by RNA interference attenuated the oncogenic behaviours and PI3K/Akt signaling, which could be partially rescued by exogenous HDGF supply. In summary, this study provides the first evidence that surface NCL transmits the oncogenic signaling of HDGF and facilitates a novel diagnostic and therapeutic target for HCC.
PMCID: PMC4599268  PMID: 25938538
hepatoma-derived growth factor; nucleolin; hepatocellular carcinoma; tumour progression
20.  Association between serum interleukin-35 levels and severity of acute pancreatitis 
Inflammatory cytokines have been reported to be associated with pathogenesis of acute pancreatitis. The aim of this study was to measure the serum IL-35 levels in patients with acute pancreatitis and analyze the relationship between IL-35 levels and the disease severity. Thirty-two patients with acute pancreatitis and 32 healthy control subjects were included into the study. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay upon admission and the following seven days. The relationships with severity and etiology during the clinical course were analyzed. Serum IL-35 levels in patients with acute pancreatitis at the time of admission (5.25±0.37 ng/mL) were significantly higher than those in healthy controls (1.93±0.16 ng/mL, P<0.001). Moreover, serum IL-35 levels in patients with severe attacks (7.15±0.48 ng/mL) were significantly higher than those with moderately severe attacks (5.14±0.49 ng/mL, P=0.01) and mild attacks (3.69±0.53 ng/mL, P<0.001). However, there was no significant difference of serum IL-35 levels among patients with acute pancreatitis due of alcohol, gallstone and idiopathy. In addition, the peak serum concentrations of IL-35 were on day 1 after admission. Our results demonstrate that increased serum IL-35 levels may be related to the inflammatory response in patients with acute pancreatitis, suggesting that IL-35 may be used for a potential biomarker of acute pancreatitis.
PMCID: PMC4509231  PMID: 26221286
Acute pancreatitis; serum interleukin-35; biomarker
21.  Periodontal disease associates with higher brain amyloid load in normal elderly 
Neurobiology of aging  2014;36(2):627-633.
Background
The accumulation of amyloid β plaques (Aβ) is a central feature of Alzheimer’s disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory/infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD.
Methods
Thirty-eight cognitively normal, healthy, community residing elderly (mean age 61; 68% female) were examined in an Alzheimer’s Disease research center and a University-based Dental School. Linear regression models (adjusted for age, ApoE and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using 11C-PIB PET imaging.
Results
After adjusting for confounders, clinical attachment loss (≥ 3mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased 11C-PIB uptake in Aβ vulnerable brain regions (p=0.002).
Conclusion
We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with prior animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations.
doi:10.1016/j.neurobiolaging.2014.10.038
PMCID: PMC4399973  PMID: 25491073
Alzheimer’s disease; infection; inflammation; periodontal disease; brain amyloid; PIB-PET; cognition
22.  Unexpected esophageal diseases appeared in thyroid resections 
Objective
In order to avoid the misdiagnosis of thyroid diseases, we need to discuss the clinical features and diagnostic methods of cervical esophageal cancer and Zenker’s diverticulum.
Methods
The clinical and laboratory data of seven cases were reviewed retrospectively, and in all cases, esophageal-related diseases were misdiagnosed as thyroid diseases preoperatively. Among them, two cases were cervical esophageal cancer metastasized to thyroids but initially, they were misdiagnosed as thyroid cancer. The other five cases were Zenker’s diverticulum, but were originally diagnosed as nodular goiter, and two out of the five cases were found with calcification. They were all detected by ultrasound examination without any clinical feature of esophageal diseases. Previous literatures only reported five cases of thyroid metastasis and three cases of Zenker’s diverticulum.
Results
In both cases where cervical esophageal cancer metastasized to thyroid, anterior cervical neoplasm biopsy and surgical removal were performed followed by postoperative radiotherapy and chemotherapy. Both patients died from esophageal cancers in 7 and 15 months postoperatively. All five cases of Zenker’s diverticulum received excision and repair without any postoperative complication or recurrence in the following 2 to 7 years.
Conclusions
Cervical esophageal cancer and Zenker’s diverticulum may be misdiagnosed as thyroid disease. Careful and comprehensive diagnostic tests would be required to avoid misdiagnosis.
doi:10.1186/s12957-015-0542-5
PMCID: PMC4387597  PMID: 25888936
Cervical esophageal cancer; Zenker’s diverticulum; Thyroid misdiagnosis
23.  Benchmarking a Test of Temporal Orientation with Data from American and Taiwanese Persons with Alzheimer's Disease and American Normal Elderly 
Neuroepidemiology  2004;24(0):110-116.
Orientation questions are readily incorporated into longitudinal population surveys, but their value as a screening tool for cognitive impairment is uncertain. We evaluated the screening value of four orientation-to-time items (TTO) from the Mini-Mental State Examination (MMSE) by determining their association with full-scale MMSE scores. Data collected under protocols with strict eligibility criteria in the US (64 normal elderly, 242 persons with probable Alzheimer's disease) and Taiwan (241 persons with probable Alzheimer's disease) were analyzed. The TTO and full-scale MMSE scores were significantly correlated (p < 0.05) in persons with a Clinical Dementia Rating (CDR) score of 0 or 1; this was not significant in persons with a CDR of >1 (p > 0.05). Both TTO and MMSE were significantly associated with education in persons with 0–7 years of education; some MMSE items, but none of the TTO items, were associated with education in persons with more than 7 years of education. TTO may be a useful component of cognitive screening efforts.
doi:10.1159/000081610
PMCID: PMC4377285  PMID: 15492486
Alzheimer's disease; Orientation; Dementia; longitudinal
24.  One-trial 10-item free-recall performance in Taiwanese elderly and near-elderly: A potential screen for cognitive decline 
To explore a one-trial 1 0-item free-recall test as a potential dementia screening tool, we analyzed recall scores and individualized serial position effects in near-elderly (N = 2,336) and elderly (N = 2,371) participants in a population-based survey in Taiwan. Age and sex were significantly associated with recall score [younger> older(p < 0.001); men> women (p < 0.001)]; after controlling for gender and age group, weak association between recall and education was still observed. By contrast, serial position effects (SPEs), defined for each participant and analyzed aggregated over each age group, were not associated with education and tended not to be associated with sex. Primacy effects were observed in 67 to 80 percent, and recency effects were observed in 41 to 54 percent of respondents. Because SPEs were defined for each respondent, we could determine that loss of the primacy effect was associated with significantly larger losses in total recall score in elderly persons who had exhibited both SPEs at the first survey, as compared to those who maintained both SPEs at successive surveys (p < 0.01). Elderly subjects showed slight longitudinal decline infree recall. A one-trial10-itemfree-recall test demonstrated age-related cognitive decline in this Taiwanese population survey cohort; SPEs at the individual level may be useful markers for important cognitive change and warrant further study and benchmarking against valid and reliable tests of memory and cognitive decline.
PMCID: PMC4375550  PMID: 16136848
serial position effects; cognitive decline; primacy effect; dementia; education
25.  Extensive Genomic Variability of Knops Blood Group Polymorphisms Is Associated with Sickle Cell Disease in Africa 
Sickle cell disease (SCD) is a multisystem disorder characterized by chronic hemolytic anemia, vaso-occlusive crises, and marked variability in disease severity. Patients require transfusions to manage disease complications, with complements, directed by complement regulatory genes (CR1) and its polymorphisms, implicated in the development of alloantibodies. We hypothesize that CR1 polymorphisms affect complement regulation and function, leading to adverse outcome in SCD. To this end, we determined the genomic diversity of complement regulatory genes by examining single nucleotide polymorphisms associated with Knops blood group antigens. Genomic DNA samples from 130 SCD cases and 356 control Africans, 331 SCD cases and 497 control African Americans, and 254 Caucasians were obtained and analyzed, utilizing a PCR—RFLP (polymerase chain reaction–restriction fragment length polymorphism) assay. Analyzing for ethnic diversity, we found significant differences in the genotypic and allelic frequencies of Sl1/Sl2 (rs17047661) and McCa/b (rs17047660) polymorphisms between Africans, African Americans, and Caucasians (P < 0.05). The homozygote mutant variants had significantly higher frequencies in Africans and African Americans but were insignificant in Caucasians (80.2% and 59.6% vs 5.9% for Sl1/2; and 36% and 24% vs 1.8% for McCa/b). With SCD, we did not detect any difference among cases and controls either in Africa or in the United States. However, we found significant difference in genotypic (P < 0.0001) and allelic frequencies (P < 0.0001) of Sl1/Sl2 (rs17047661) and McCa/b (rs17047660) polymorphisms between SCD groups from Africa and the United States. There was no difference in haplotype frequencies of these polymorphisms among or between groups. The higher frequency of CR1 homozygote mutant variants in Africa but not United States indicates a potential pathogenic role, possibly associated with complicated disease pathophysiology in the former and potentially protective in the latter. The difference between sickle cell groups suggests potential genetic drift or founder effect imposed on the disease in the United States, but not in Africa, and a possible confirmation of the ancestral susceptibility hypothesis. The lower haplotype frequencies among sickle cell and control populations in the United States may be due to the admixture and the dilution of African genetic ancestry in the African American population.
doi:10.4137/EBO.S23132
PMCID: PMC4357628  PMID: 25788827
complement receptor 1; sickle cell disease; polymorphisms; pathophysiology; Africa; United States; evolution; ancestry

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