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1.  PKM2 Regulates the Warburg Effect and Promotes HMGB1 Release in Sepsis 
Nature communications  2014;5:4436.
Increasing evidence suggests the important role of metabolic reprogramming in the regulation of the innate inflammatory response, but the underlying mechanism remains unclear. Here, we provide evidence to support a novel role for the pyruvate kinase M2 (PKM2)-mediated Warburg effect, namely aerobic glycolysis, in the regulation of high mobility group box 1 (HMGB1) release. PKM2 interacts with hypoxia-inducible factor 1α (HIF1α) and activates the HIF-1α-dependent transcription of enzymes necessary for aerobic glycolysis in macrophages. Knockdown of PKM2, HIF1α, and glycolysis-related genes uniformly decreases lactate production and HMGB1 release. Similarly, a potential PKM2 inhibitor, shikonin, reduces serum lactate and HMGB1 levels and protects mice from lethal endotoxemia and sepsis. Collectively, these findings shed light on a novel mechanism for metabolic control of inflammation by regulating HMGB1 release and highlight the importance of targeting aerobic glycolysis in the treatment of sepsis and other inflammatory diseases.
doi:10.1038/ncomms5436
PMCID: PMC4104986  PMID: 25019241
2.  Spontaneous immortalization of mouse liver sinusoidal endothelial cells 
The spontaneous immortalization of cells in vitro is a rare event requiring genomic instability, such as alterations in chromosomes and mutations in genes. In the present study, we report a spontaneously immortalized liver sinusoidal endothelial cell (LSEC) line generated from mouse liver. These immortalized LSECs showed typical LSEC characteristics with the structure of transcellular fenestrations, the expression of von Willebrand factor (VWF) and the ability to uptake DiI-acetylated-low density lipoprotein (DiI-Ac-LDL). However, these immortalized LSECs lost the ability to form capillary-like structures, and showed clonal and multilayer growth without contact inhibition. Moreover, their proliferation rate increased with the increase in the number of passages. In addition, these cells obained the expression of CD31 and desmin, and showed an upregulation of p53 protein expression; however, their karyotype was normal, and they could not form colonies in soft agar or tumors in SCID mice. In conclusion, in the present study, we successfully established a spontaneously immortalized LSEC line.
doi:10.3892/ijmm.2015.2067
PMCID: PMC4314414  PMID: 25585915
spontaneous immortalization; liver sinusoidal endothelial cell; proliferation; phenotype
3.  Precisely Tunable Engineering of Sub-30 nm Monodisperse Oligonucleotide Nanoparticles 
Advancement of RNAi therapies is mainly hindered by the development of efficient delivery vehicles. The ability to create small size (< 30 nm) oligonucleotide nanoparticles is essential for many aspects of the delivery process but is often overlooked. In this report, we describe di-block star polymers that can reproducibly complex double-stranded oligonucleotides into monodisperse nanoparticles with 15, 23 or 30 nm in diameter. The polymer-nucleic acid nanoparticles have a core-shell architecture with dense PEG brush coating. We characterized these nanoparticles using ITC, DLS, FRET, FCS, TIRF and TEM. In addition to small size, these nanoparticles have neutral zeta potentials making the presented polymer architecture a very attractive platform for investigation of yet poorly studied polyplex size range for siRNA and antisense oligonucleotide delivery applications.
doi:10.1021/ja408879b
PMCID: PMC3912943  PMID: 24344996
4.  Efficacy of prophylactic intravenous ondansetron on the prevention of hypotension during cesarean delivery: a dose-dependent study 
Objective: This study was to determine the optimal dosage of ondansetron for preventing maternal hypotension during cesarean delivery. Methods: One hundred and fifty parturient women scheduled for elective cesarean section were randomly assigned to five groups (n=30). Five minutes prior to spinal anesthesia, women were injected with 5 ml of physiological saline (S), 2 mg (O2), 4 mg (O4), 6 mg (O6), or 8 mg (O8) of ondansetron in saline, respectively. Maternal blood pressure and heart rate were measured at 2-min intervals for 30 min. The serum parameters in umbilical cord blood were analyzed after delivery. Results: Compared with group S, the incidence of maternal hypotension was significantly lower in groups O4 and O6 (P < 0.05). The umbilical venous pH was significantly higher in group O4 (P < 0.05); while the partial pressure of carbon dioxide (Pco2) was significantly lower in groups O4, O6, and O8 (P < 0.05); and the bicarbonate (Hco3 -) and base excess in extracellular fluid (BEecf) were significantly lower in groups O6 and O8 (P < 0.05). Moreover, minimal changes of systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were observed in group O4 (P < 0.05). Conclusion: The optimal dose of ondansetron preloading was 4 mg during cesarean delivery.
PMCID: PMC4307470  PMID: 25664023
Ondansetron; hypotension; spinal anesthesia; optimal dose
5.  The Masquelet Technique for Membrane Induction and the Healing of Ovine Critical Sized Segmental Defects 
PLoS ONE  2014;9(12):e114122.
The healing of critical sized segmental defects is an ongoing clinical problem. No method has achieved pre-eminence. The Masquelet technique is a relatively new innovation involving the induction of a fibrous tissue membrane around the bone defect site taking advantage of the body’s foreign body reaction to the presence of a polymethylmethacrylate (PMMA) spacer. The aim of this study was to investigate the properties and characteristics of this induced membrane and its effectiveness when used in conjunction with allograft or an allograft/autograft mix as filler materials in an ovine critical sized defect model. The resultant induced membrane was found to be effective in containing the graft materials in situ. It was demonstrated to be an organised pseudosynovial membrane which expressed bone morphogenic protein 2 (BMP2), transforming growth factor- beta (TGFβ), vascular endothelial growth factor (VEGF), von Willerbrand factor (vWF), interleukin 6 (IL-6) and interleukin 8 (IL-8). While more new bone growth was evident in the test groups compared to the controls animals at 12 weeks, the volumes were not statistically different and no defects were fully bridged. Of the two graft material groups, the allograft/autograft mix was shown to have a more rapid graft resorption rate than the allograft only group. While the Masquelet technique proved effective in producing a membrane to enclose graft materials, its ability to assist in the healing of critical sized segmental defects when compared to empty controls remained inconclusive.
doi:10.1371/journal.pone.0114122
PMCID: PMC4252083  PMID: 25461340
6.  Decreased SCF/c-kit signaling pathway contributes to loss of interstitial cells of Cajal in gallstone disease 
Cholecystolithiasis is a common disease, and gallbladder dysmotility is considered as a pivotal pathogenesis. Interstitial cells of Cajal (ICCs) serve as pacemakers and mediators of neuromuscular transmission for gastrointestinal motility. Reduction of ICCs has been reported in gallstone diseases. However, there are no reasonable mechanisms for the cholecystolithiasis-associated loss of ICCs in humans. Stem cell factor (SCF) and its ligand c-kit are essential for normal development and survival of ICCs. To date, little is known about the SCF/c-kit signaling pathway in gallstone diseases. The purpose of this study was to investigate the role of the SCF/c-kit signaling pathway in the loss of ICCs in cholecystolithiasis. Data from 18 patients with gallstones and 14 individuals without gallstones were compared. The gallbladder contractility was assessed by measuring the gallbladder ejection fraction (GEF) ultrasonographically. Tissues samples were obtained during surgery, changes of ICC quantities were analyzed by immunohistochemistry, and the mRNA and protein expression of SCF and c-kit were detected by Real-Time PCR and Western-blot analysis. Compared with the controls, the GEF was significantly reduced in the gallstone group, and decreased number of ICCs was present obviously in the gallstone group. Furthermore, the mRNA and protein expression of SCF and c-kit were significantly attenuated in the gallstone group. These data indicate that gallbladder motility may be affected by reduction of ICCs in gallstone disease. Additionally, the decreased of SCF/c-kit signaling pathway play an important role in the loss of ICCs.
PMCID: PMC4276177  PMID: 25550919
Gallstone disease; interstitial cells of Cajal; stem cell factor; c-kit; gallbladder motility
7.  Assessment of Atrial Fibrillation and Vulnerability in Patients with Wolff-Parkinson-White Syndrome Using Two-Dimensional Speckle Tracking Echocardiography 
PLoS ONE  2014;9(11):e108315.
Purpose
The aim was to assess atrial fibrillation (AF) and vulnerability in Wolff-Parkinson-White (WPW) syndrome patients using two-dimensional speckle tracking echocardiography (2D-STE).
Methods
All patients were examined via transthoracic echocardiography and 2D-STE in order to assess atrial function 7 days before and 10 days after RF catheter ablation. A postoperative 3-month follow-up was performed via outpatient visit or telephone calls.
Results
Results showed significant differences in both body mass index (BMI) and supraventricular tachycardia (SVT) duration between WPW patients and DAVNP patients (both P<0.05). Echocardiography revealed that the maximum left atrial volume (LAVmax) and the left ventricular mass index (LVMI) in diastole increased noticeably in patients with WPW compared to patients with DAVNP both before and after ablation (all P<0.05). Before ablation, there were obvious differences in the levels of SRs, SRe, and SRa from the 4-chamber view (LA) in the WPW patients group compared with patients in the DAVNP group (all P<0.05). In the AF group, there were significant differences in the levels of systolic strain rate (SRs), early diastolic strain rate (SRe), and late diastolic strain rate (SRa) from the 4-chamber view (LA) both before and after ablation (all P<0.05). In the non-AF group, there were decreased SRe levels from the 4-chamber view (LA/RA) pre-ablation compared to post-ablation (all P<0.05).
Conclusion
Our findings provide convincing evidence that WPW syndrome may result in increased atrial vulnerability and contribute to the development of AF. Further, RF catheter ablation of AAV pathway can potentially improve atrial function in WPW syndrome patients. Two-dimensional speckle tracking echocardiography imaging in WPW patients would be necessary in the evaluation and improvement of the overall function of RF catheter ablation in a long-term follow-up period.
doi:10.1371/journal.pone.0108315
PMCID: PMC4232256  PMID: 25397668
8.  Theoretical design of multi-colored semi-transparent organic solar cells with both efficient color filtering and light harvesting 
Scientific Reports  2014;4:7036.
Solar cells incorporated with multi-coloring capability not only offer an aesthetic solution to bridge the gap between solar modules and building decorations but also open up the possibility for self-powered colorful display. In this paper, we proposed a multi-colored semi-transparent organic solar cells (TOSCs) design containing metallic nanostructures with the both high color purity and efficiency based on theoretical considerations. By employing guided mode resonance effect, the multi-colored TOSC behave like an efficient color filter that selectively transmits light with the desired wavelengths and generates electricity with light of other wavelengths. Broad range of coloring and luminosity adjusting for the transmission light can be achieved by simply tuning the period and the duty cycle of the metallic nanostructures. Furthermore, accompanying with the efficient color filtering characteristics, the optical absorption of TOSCs was improved due to the marked suppression of transmission loss at the off-resonance wavelengths and the increased light trapping in TOSCs. The mechanisms of the light guiding in photoactive layer and broadband backward scattering from the metallic nanostructures were identified to make an essential contribution to the improved light-harvesting. By enabling efficient color control and high efficiency simultaneously, this approach holds great promise for future versatile photovoltaic energy utilization.
doi:10.1038/srep07036
PMCID: PMC4229659  PMID: 25391756
9.  Overexpression of EpCAM and Trop2 in pituitary adenomas 
We sought to investigate the expression of EpCAM and Trop2 in Pituitary adenomas (PAs) and study the correlation of protein expression with invasiveness, proliferation, clinical functioning, recurrence/progression, and some other factors. We investigated the expression of EpCAM and Trop2 in 74 samples of PAs by immunohistochemistry and made correlative analysis of protein overexpression with clinicopathological parameters. Follow-up data was analyzed for recurrence/progression with Kaplan-Meier method and Multivariate Cox regression analysis. Immunohistochemistry results showed that overexpression rates of EpCAM and Trop2 were 51/74 (68.9%) and 43/74 (58.1%), respectively. For both EpCAM and Trop2, PAs with invasiveness showed a higher overexpression rate than PAs without invasiveness (PEpCAM = 0.001; PTrop2 = 0.006). Nonfunctional Pituitary adenomas (NFPAs) demonstrated a higher EpCAM overexpression than functional Pituitary adenomas (FPAs) (P = 0.026). Both EpCAM and Trop2 overexpression correlated significantly with expression of proliferation factor Ki-67 (PEpCAM = 0.011; PTrop2 = 0.000), but not with gender and age. Follow-up analysis revealed that Trop2 overexpression was a significantly predictive factor for recurrence/progression by means of Kaplan-Meier method d (P = 0.028) and Multivariate Cox regression analysis (P = 0.025). This study reveals that both EpCAM and Trop2 overexpression in PAs correlate significantly with invasiveness and proliferation. EpCAM presents a potential target for differential diagnosis and immunotherapy for NFPAs. Follow-up analysis shows that Trop2 is a predictive factor for recurrence/progression for PAs.
PMCID: PMC4270592  PMID: 25550831
Pituitary adenomas; EpCAM; Trop2
10.  NK Cell Phenotypic Modulation in Lung Cancer Environment 
PLoS ONE  2014;9(10):e109976.
Background
Nature killer (NK) cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment.
Materials and methods
Our study analyzed the change about NK cells surface markers (NK cells receptors) through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse.
Results
We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently.
Conclusions
The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy.
doi:10.1371/journal.pone.0109976
PMCID: PMC4192363  PMID: 25299645
11.  A Sheep Model for Cancellous Bone Healing 
Frontiers in Surgery  2014;1:37.
Appropriate well-characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14 mm) of fixed depth (25 mm) were compared in both skeletally immature (18-month-old) and aged sheep (5-year-old). In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at 4 weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using μCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects with woven bone normally forming near the periphery of the defect. Bone volume fraction [bone volume (BV)/TV] significantly decreased with an increasing defect diameter. Actual BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11 mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal and encourages a reduction in animal numbers required for preclinical research.
doi:10.3389/fsurg.2014.00037
PMCID: PMC4286987  PMID: 25593961
ovine; sheep; model; bone healing; micro ct; age; hard tissue; histology
12.  Overactivation of Mitogen-Activated Protein Kinase and Suppression of Mitofusin-2 Expression Are Two Independent Events in High Mobility Group Box 1 Protein–Mediated T Cell Immune Dysfunction 
High mobility group box 1 protein (HMGB1), a critical proinflammatory cytokine, has recently been identified to be an immunostimulatory signal involved in sepsis-related immune dysfunction when released extracellularly, but the potential mechanism involved remains elusive. Here, we showed that the treatment with HMGB1 in vitro inhibited T lymphocyte immune response and expression of mitofusin-2 (Mfn-2; a member of the mitofusin family) in a dose- and time-dependent manner. Upregulation of Mfn-2 expression attenuated the suppressive effect of HMGB1 on T cell immune function. The phosphorylation of both extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) was markedly upregulated by treating with high amount of HMGB1, while pretreatment with ERK1/2 and p38 MAPK-specific inhibitors (U0126 and SB203580) could attenuate suppression of T cell immune function and nuclear factor of activated T cell (NFAT) activation induced by HMGB1, respectively. HMGB1-induced activity of ERK1/2 and p38 was not fully inhibited in the presence of U0126 or SB203580. Interestingly, overexpression of Mfn-2 had no marked effect on HMGB1-mediated activation of MAPK, but could attenuate the suppressive effect of HMGB1 on the activity of NFAT. Thus, the mechanisms involved in HMGB1-induced T cell immune dysfunction in vitro at least partly include suppression of Mfn-2 expression, overactivation of ERK1/2, p38 MAPK, and intervention of NFAT activation, while the protective effect of Mfn-2 on T cell immune dysfunction induced by HMGB1 is dependent on other signaling pathway associated with NFAT, but not MAPK. Taken together, we conclude that overactivation of MAPK and suppression of Mfn-2 expression are two independent events in HMGB1-mediated T cell immune dysfunction.
doi:10.1089/jir.2012.0054
PMCID: PMC3760027  PMID: 23697559
13.  Variation in copper and zinc tolerance and accumulation in 12 willow clones: implications for phytoextraction*  
Willows (Salix spp.) have shown high potential for the phytoextraction of heavy metals. This study compares variations in copper (Cu) and zinc (Zn) tolerance and accumulation potential among 12 willow clones grown in a nutrient solution treated with 50 μmol/L of Cu or Zn, respectively. The results showed differences in the tolerance and accumulation of Cu and Zn with respect to different species/clones. The biomass variation among clones in response to Cu or Zn exposure ranged from the stimulation of growth to inhibition, and all of the clones tested showed higher tolerance to Cu than to Zn. The clones exhibited less variation in Cu accumulation but larger variation in Zn accumulation. Based on translocation factors, it was found that most of the Cu was retained in the roots and that Zn was more mobile than Cu for all clones. It is concluded that most willow clones are good accumulators of Zn and Cu.
doi:10.1631/jzus.B1400029
PMCID: PMC4162880  PMID: 25183033
Salix spp.; Copper; Zinc; Accumulation; Tolerance; Hydroponic screening
14.  Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function 
Acta Pharmacologica Sinica  2014;35(9):1167-1176.
Aim:
The receptor of advanced glycation end products (RAGE) participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function.
Methods:
Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibody (1 mg/kg, iv) at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell (DC) and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury.
Results:
Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats (6.67% in the model group; 33.33% in anti-RAGE group). Treatment with the antibody also attenuated the multiple organ dysfunction syndrome (MODS) following the thermal injury, as shown by significant decreases in the organ dysfunction markers, including serum ALT, AST, blood urea nitrogen, creatinine and CK-MB. Moreover, treatment with the antibody significantly promoted DC maturation and T cell activation in the spleens of thermally injured rats.
Conclusion:
Blockade of the RAGE axis by the antibody effectively ameliorated MODS and improved the survival rate in thermally injured rats, which may be due to modulation of cellular immune function.
doi:10.1038/aps.2014.56
PMCID: PMC4155528  PMID: 25152026
RAGE; anti-RAGE antibody; burns; thermal injury; multiple organ dysfunction syndrome; cytokine; inflammation; immune response; dendritic cell; T cell
15.  Enteric glial cells and their role in the intestinal epithelial barrier 
World Journal of Gastroenterology : WJG  2014;20(32):11273-11280.
The intestinal epithelium constitutes a physical and functional barrier between the external environment and the host organism. It is formed by a continuous monolayer of intestinal epithelial cells maintained together by intercellular junctional complex, limiting access of pathogens, toxins and xenobiotics to host tissues. Once this barrier integrity is disrupted, inflammatory disorders and tissue injury are initiated and perpetuated. Beneath the intestinal epithelial cells lies a population of astrocyte-like cells that are known as enteric glia. The morphological characteristics and expression markers of these enteric glia cells were identical to the astrocytes of the central nervous system. In the past few years, enteric glia have been demonstrated to have a trophic and supporting relationship with intestinal epithelial cells. Enteric glia lesions and/or functional defects can be involved in the barrier dysfunction. Besides, factors secreted by enteric glia are important for the regulation of gut barrier function. Moreover, enteric glia have an important impact on epithelial cell transcriptome and induce a shift in epithelial cell phenotype towards increased cell adhesion and cell differentiation. Enteric glia can also preserve epithelial barrier against intestinal bacteria insult. In this review, we will describe the current body of evidence supporting functional roles of enteric glia on intestinal barrier.
doi:10.3748/wjg.v20.i32.11273
PMCID: PMC4145765  PMID: 25170211
Enteric glia cells; Intestinal epithelial cells; Intestinal barrier function; Tight junctions
16.  Rapid Diagnosis of Childhood Pulmonary Tuberculosis by Xpert MTB/RIF Assay Using Bronchoalveolar Lavage Fluid 
BioMed Research International  2014;2014:310194.
In order to evaluate the diagnostic accuracy of the Xpert MTB/RIF assay on childhood pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF), we evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF assay using BALF in comparison with acid-fast bacilli (AFB) microscopy and Mycobacterium tuberculosis (MTB) culture for diagnosing childhood PTB using Chinese “composite clinical reference standard” (CCRS) as reference standard. Two hundred fifty-five children with suspected PTB were enrolled at Beijing Children's Hospital from September 2010 to July 2013. Compared with Chinese CCRS, the sensitivity of AFB microscopy, MTB culture, and Xpert MTB/RIF assay was 8.4%, 28.9%, and 53.0%, respectively. The specificity of three assays was all 100%. Xpert MTB/RIF assay could detect 33.9% of cases with negative MTB culture, and 48.7% of cases with negative AFB microscopy. Younger age (<3 years), absence of BCG scar, and contact with TB patient were found significantly associated with a positive result of Xpert MTB/RIF assay. In conclusion, Xpert MTB/RIF assay using BALF can assist in diagnosing childhood PTB much faster when fiberoptic bronchoscopy is necessary according to the chest radiograph.
doi:10.1155/2014/310194
PMCID: PMC4140106  PMID: 25165698
17.  Chloroquine Inhibits HMGB1 Inflammatory Signaling and Protects Mice from Lethal Sepsis 
Biochemical pharmacology  2013;86(3):410-418.
Sepsis is caused by an overwhelming immune response to bacterial infection. The discovery of high mobility group box 1 (HMGB1) as a late mediator of lethal sepsis has prompted investigation into the development of new therapeutics which specifically target this protein. Here, we show that chloroquine, an anti-malarial drug, prevents lethality in mice with established endotoxemia or sepsis. This effect is still observed even if administration of chloroquine is delayed. The protective effects of chloroquine were mediated through inhibition of HMGB1 release in macrophages, monocytes, and endothelial cells, thereby preventing its cytokine-like activities. As an inhibitor of autophagy, chloroquine specifically inhibited HMGB1-induced Iκ-B degradation and NF-κB activation. These findings define a novel mechanism for the anti-inflammatory effects of chloroquine and also suggest a new potential clinical use for this drug in the setting of sepsis.
doi:10.1016/j.bcp.2013.05.013
PMCID: PMC3713089  PMID: 23707973
HMGB1; chloroquine; sepsis; autophagy; NF-κB; Beclin 1
18.  Early channel transurethral resection of the prostate for patients with urinary retention after brachytherapy 
Objective: It is recommended that transurethral resection of the prostate (TURP) after brachytherapy should not be performed at an early stage after implantation. Herein we report our experiences and the results of channel TURP (cTURP) within six months post-implant for patients with refractory urinary retention. Methods: One hundred and ninety patients with localized prostate cancer of clinical stages T1c to T2c were treated by brachytherapy as monotherapy at our institution from February 2009 to July 2013. Nine patients who developed refractory urinary retention and underwent cTURP within six months after brachytherapy were retrospectively reviewed and analyzed. Results: The median interval between prostate brachytherapy and cTURP was three months (range 1.5 to 5.0 months). There were no intraoperative or postoperative complications and no incontinence resulting from the surgery. All urinary retention was relieved per the American Brachytherapy Society urinary symptom score. With a mean follow-up time of 16 months (range 6 to 26 months) after cTURP, no patient experienced biochemical recurrence. The mean serum prostate-specific antigen (PSA) of the patients who underwent cTURP was 0.42 ng/ml (range 0.08 to 0.83 ng/ml) at the end of their follow-up. Conclusions: Early cTURP was found to be safe and effective in relieving urinary retention after brachytherapy and could be performed without compromising its therapeutic efficacy.
doi:10.1631/jzus.B1400100
PMCID: PMC4129097  PMID: 25091995
Prostate cancer; Brachytherapy; Transurethral resection of the prostate (TURP)
19.  Rechallenge with pemetrexed-based chemotherapy improves the survival of patients with advanced non-squamous non-small-cell lung cancer 
Molecular and Clinical Oncology  2014;2(6):953-959.
Rechallenge chemotherapy with pemetrexed was shown to be efficient in malignant pleural mesothelioma; however, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, we retrospectively enrolled 31 patients with non-squamous NSCLC who had achieved disease control with initial pemetrexed treatment, followed by rechallenge with pemetrexed-based chemotherapy (PBC) upon disease progression. After the rechallenge, 5 patients (16.1%) achieved partial remission (PR), 17 (54.8%) achieved stable disease (SD) and 9 (29.1%) experienced progressive disease. The treatment was generally well tolerated, with a low rate of toxicity. The median progression-free survival (PFS) was 3.8 months with the rechallenge. Patients with a PFS of ≥10 months with initial PBC exhibited longer PFS and overall survival (OS) with the rechallenge compared to those with a PFS of <10 months with initial PBC (PFS: 6.2±0.33 vs. 3.1±0.26 months, respectively; P=0.011; and OS, 19.8±3.2 vs. 9.2±1.1 months, respectively; P=0.005). The time from the termination of initial PBC to disease progression was also associated with survival after the rechallenge. However, the response to initial PBC (PR vs. SD) did not affect PFS after the rechallenge. No significant differences were observed in thymidylate synthase expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene fusion, or epithelial growth factor receptor mutation status between pemetrexed-sensitive and pemetrexed-resistant patients. Our results demonstrated that rechallenge with PBC was well tolerated and survival after the rechallenge was associated with survival during initial PBC. Therefore, patients with a PFS of ≥10 months or time-to-disease progression ≥3 months may be considered as candidates for pemetrexed rechallenge.
doi:10.3892/mco.2014.359
PMCID: PMC4179803  PMID: 25279180
pemetrexed; rechallenge; non-small-cell lung cancer; overall survival; adverse effects
20.  Two Cases of Severe Preeclampsia Were Diagnosed with HELLP Postpartum after Caesarian Section 
HELLP occurs in 0.5%–0.9% of all pregnancies. About 30% of the cases happen within 48 hours after delivery. Women with postpartum HELLP syndrome have significantly higher incidences of complications. Because of the absence of classical signs of preeclampsia, it can confuse physicians and lead to delay in diagnosis. Therefore, it is associated with serious maternal morbidity. We present two cases of acute postpartum HELLP syndrome after caesarean section following severe preeclampsia. Our cases were successfully managed with the timely diagnosis and therapy.
doi:10.1155/2014/747510
PMCID: PMC4131095  PMID: 25143846
21.  Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1 
The Journal of pathology  2013;230(2):184-193.
Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down-regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation.
doi:10.1002/path.4169
PMCID: PMC4080639  PMID: 23355073
prostate cancer; tumour; suppression; metallothionein; histone methylation
22.  Meta-Analysis of the Adverse Effects of Long-Term Azithromycin Use in Patients with Chronic Lung Diseases 
The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.
doi:10.1128/AAC.02067-13
PMCID: PMC3910718  PMID: 24189261
23.  Prevalence and Fimbrial Genotype Distribution of Poultry Salmonella Isolates in China (2006 to 2012) 
In this study, a total of 323 Salmonella enterica strains were isolated from 3,566 rectal swab samples of 51 poultry farms in seven regions of 12 provinces of China between 2006 and 2012. The prevalences of Salmonella sp. carriage were 12.4% in geese (66 positive/533 samples), 10.4% in turkeys (32/309), 9.8% in chickens (167/1,706), 6.8% in ducks (41/601), and 4.1% in pigeons (17/417), respectively. These isolates belonged to 20 serovars, in which the most frequent serovars were S. enterica serovar Gallinarum biovar Pullorum (herein, S. Pullorum) (55 isolates, 17.0%), S. enterica serovar Typhimurium (50 isolates, 15.5%), and S. enterica serovar Enteritidis (39 isolates, 12.1%). Overall, S. Typhimurium was the most commonly detected serovar; among the individual species, S. Pullorum was most commonly isolated from chickens, S. Enteritidis was most common in ducks, S. Typhimurium was most common in geese and pigeons, and S. enterica serovar Saintpaul was most common in turkeys. PCR determination of 20 fimbrial genes demonstrated the presence of bcfD, csgA, fimA, stdB, and sthE genes and the absence of staA and stgA genes in these isolates, and other loci were variably distributed, with frequency values ranging from 11.8 to 99.1%. These 323 Salmonella isolates were subdivided into 41 different fimbrial genotypes, and of these isolate, 285 strains (88.2%) had 12 to 14 fimbrial genes. Our findings indicated that the Salmonella isolates from different poultry species were phenotypically and genetically diverse and that some fimbrial genes are more frequently associated with serovars or serogroups.
doi:10.1128/AEM.03223-13
PMCID: PMC3911082  PMID: 24242234
24.  Laparoendoscopic single-site distal pancreatectomy in pigs 
AIM: To explore the technique for laparoendoscopic single-site distal pancreatectomy.
METHODS: Laparoendoscopic single-site spleen-preserving distal pancreatectomy was performed in pigs using a novel flexible multichannel port, a curved laparoscopic multifunctional operative device and a fish hook retractor, which provided a favorable operative field.
RESULTS: Six pigs were involved in this study, and five survived the procedure. The first animal died following injury to the superior mesenteric vein and uncontrolled intraoperative bleeding. Except for this failure, the mean operative time was 155 min (range: 102-236 min). A steep learning curve was observed in the study, with a mean operative time of 177 min in the first two operations vs 134 min in the last three operations. The mean blood loss was 50 mL, and the postoperative course was uneventful. The animals were sacrificed three weeks after the procedures, and no pancreatic leakage or abdominal infection was found macroscopically.
CONCLUSION: Laparoendoscopic single-site distal pancreatectomy is a safe and feasible procedure and can be implemented in humans in selected cases at qualified surgical centers.
doi:10.3748/wjg.v20.i22.6878
PMCID: PMC4051927  PMID: 24944478
Laparoendoscopic single-site surgery; LESS; Pancreatectomy; Fish hook retraction; Curved laparoscopic multifunctional operative device
25.  Inhibition of prostate cancer growth and metastasis using small interference RNA specific for minichromosome complex maintenance component 7 
Cancer gene therapy  2010;17(10):694-699.
Minichromosome complex maintenance component 7 (MCM7) is a critical component of DNA replication licensing. Amplification and overexpression of MCM7 leads to high rate of prostate cancer metastasis. Recent studies indicate that MCM7 genome encodes a putative “super-oncogene” cluster including MCM7 oncogene and a miRNA cluster that knocks down the expression of several critical tumor suppressor genes. In this study, we constructed a vector that constitutively expresses siRNA specific for MCM7. Introduction of this vector into prostate cancer cell lines PC3 or Du145 decreases the expression of MCM7 by 80%. The vector inhibits DNA synthesis and generates growth arrest of these cancer cells. SCID mice were xenografted PC3 or Du145 tumors, and subsequently treated with this vector through tail vein injection with polyethylenimine (PEI). The animals had dramatically smaller tumor volume, less metastasis and better survival rate in comparison with the controls. As a result, intervention of MCM7 expression using siRNA approach may hold the promise for treating androgen refractory prostate cancer.
doi:10.1038/cgt.2010.25
PMCID: PMC4041301  PMID: 20539323
MCM7; siRNA knock-down; prostate; cancer; expression

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