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1.  The value of ratio of hCG, progesterone in local blood of pregnancy location versus venous blood in the diagnosis of ectopic pregnancy 
Objective: The aim of this study is to combine the ratios of venous serum/colporrhagia and hemoperitoneum/venous serum of human chorionic gonadotropin (hCG) and Progesterone (P) to generate and evaluate a new method to improve the prognosis of Ectopic pregnancy (EP). Methods: For patients with curettage procedure, curettage material and venous blood were obtained at the same time. For patients receiving culdocentesis and laparoscopic exploration, abdominal fluid and venous blood samples were obtained synchronously during surgery. Results: The sensitivity and specificity of Rp/v-hCG>1.0 and Rp/v-P>1.0 for diagnosis of EP was 88.2% and 80.71%, 93.8% and 87.53%, respectively. The sensitivity of parallel test (Rp/v-hCG>1.0 or Rp/v-P>1.0) was 92.23%. The specificity of serial test (Rp/v-hCG>1.0 and Rp/v-P>1.0) was 100%. For the area under the ROC curve of Rp/v-hCG and Rp/v-P, the parallel test and serial test were 0.91 and 0.82,0.90 and 0.87, respectively. At the determining threshold point of 1.0, the sensitivity of Rv/c-hCG and Rv/c-P for the diagnosis of EP was 56.73% and 60.01%. The specificity was 100% and 100%, respectively. The sensitivity of parallel test (Rv/c-hCG>1.0 or Rv/c-P>1.0) was 73.33%. For the area under the ROC curve of Rv/c-hCG, Rv/c-P and the parallel test was 0.78,0.80 and 0.87, respectively. Conclusions: It is proposed that EP can more rapidly and accurately be diagnosed by multiple biomarkers’ test of Rp/v-hCG>1.0 and/or Rp/v-P>1.0, as well as Rv/c-hCG>1.0 and/or Rv/c-P>1.0 via culdocentesis or curettage.
PMCID: PMC4538086  PMID: 26309611
Ectopic pregnancy; human chorionic gonadotropin; progesterone
2.  Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin 
BioMed Research International  2015;2015:291871.
Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP) has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents.
PMCID: PMC4475764  PMID: 26167481
3.  Adeno-Associated Virus-Mediated Overexpression of LARGE Rescues α-Dystroglycan Function in Dystrophic Mice with Mutations in the Fukutin-Related Protein 
Human Gene Therapy Methods  2014;25(3):187-196.
Multiple genes (e.g., POMT1, POMT2, POMGnT1, ISPD, GTDC2, B3GALNT2, FKTN, FKRP, and LARGE) are known to be involved in the glycosylation pathway of α-dystroglycan (α-DG). Mutations of these genes result in muscular dystrophies with wide phenotypic variability. Abnormal glycosylation of α-DG with decreased extracellular ligand binding activity is a common biochemical feature of these genetic diseases. While it is known that LARGE overexpression can compensate for defects in a few aforementioned genes, it is unclear whether it can also rescue defects in FKRP function. We examined adeno-associated virus (AAV)-mediated LARGE or FKRP overexpression in two dystrophic mouse models with loss-of-function mutations: (1) Largemyd (LARGE gene) and (2) FKRPP448L (FKRP gene). The results agree with previous findings that overexpression of LARGE can ameliorate the dystrophic phenotypes of Largemyd mice. In addition, LARGE overexpression in the FKRPP448L mice effectively generated functional glycosylation (hyperglycosylation) of α-DG and improved dystrophic pathologies in treated muscles. Conversely, FKRP transgene overexpression failed to rescue the defect in glycosylation and improve the phenotypes of the Largemyd mice. Our findings suggest that AAV-mediated LARGE gene therapy may still be a viable therapeutic strategy for dystroglycanopathies with FKRP deficiency.
PMCID: PMC4124536  PMID: 24635668
4.  A BHR Composite Network-Based Visualization Method for Deformation Risk Level of Underground Space 
PLoS ONE  2015;10(5):e0127088.
This study proposes a visualization processing method for the deformation risk level of underground space. The proposed method is based on a BP-Hopfield-RGB (BHR) composite network. Complex environmental factors are integrated in the BP neural network. Dynamic monitoring data are then automatically classified in the Hopfield network. The deformation risk level is combined with the RGB color space model and is displayed visually in real time, after which experiments are conducted with the use of an ultrasonic omnidirectional sensor device for structural deformation monitoring. The proposed method is also compared with some typical methods using a benchmark dataset. Results show that the BHR composite network visualizes the deformation monitoring process in real time and can dynamically indicate dangerous zones.
PMCID: PMC4444094  PMID: 26011618
5.  Interleukin-8 for Diagnosis of Neonatal Sepsis: A Meta-Analysis 
PLoS ONE  2015;10(5):e0127170.
Neonatal sepsis (NS) is a life-threatening disorder and an important cause of morbidity and mortality in neonates. Previous studies showed that interleukin 8 (IL-8) may effectively and rapidly diagnose NS.
We conducted the systematic review and meta-analysis to investigate the diagnostic value of the IL-8 in NS.
The literature was searched in PUBMED, EMBASE, Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October 1998 to January 2014 using set search criteria. Each included study was evaluated by quality assessment of diagnostic accuracy studies tool. Two investigators independently extracted the data and study characteristics, and disagreements, if any, were resolved by consensus. Meta-disc software was used to calculate the pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR), I² or Cochrane Q to test heterogeneity, and meta-regression to investigate the source of heterogeneity. Funnel plots were used to test the potential presence of publication bias. False-positive report probability (FPRP) was calculated to confirm the significance of the results.
Eight studies (548 neonates) were included in this meta-analysis. The pooled sensitivity and specificity of IL-8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis of NS. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) was 21.64 and 0.8908 (Q*=0.8215), respectively. The diagnostic threshold analysis showed that there was no threshold effect. The meta-regression analysis showed the cut-off, QUADAS and onset time have no effect on the heterogeneity. The funnel plots showed the existence of publication bias.
Meta-analysis showed IL-8 had a moderate accuracy (AUC=0.8908) for the diagnosis of NS. IL-8 is a helpful biomarker for early diagnosis of NS. However, we should combine the results with clinical symptoms and signs, laboratory and microbial results.
PMCID: PMC4440704  PMID: 25996378
6.  Molecular Cloning and Characterisation of Farnesyl Pyrophosphate Synthase from Tripterygium wilfordii 
PLoS ONE  2015;10(5):e0125415.
Farnesylpyrophosphate synthase (FPS) catalyzes the biosynthesis of farnesyl pyrophosphate (FPP), which is an important precursor of sesquiterpenoids such as artemisinin and wilfordine. In the present study, we report the molecular cloning and characterization of two full-length cDNAs encoding FPSs from Tripterygium wilfordii (TwFPSs). TwFPSs maintained their capability to synthesise FPP in vitro when purified as recombinant proteins from E. coli. Consistent with the endogenous role of FPS in FPP biosynthesis, TwFPSs were highly expressed in T. wilfordii roots, and were up-regulated upon methyl jasmonate (MeJA) treatment. The global gene expression profiles suggested that the TwFPSs might play an important regulatory role interpenoid biosynthesis in T. wilfordii, laying the groundwork for the future study of the synthetic biology of natural terpene products.
PMCID: PMC4418688  PMID: 25938487
7.  Evaluation of Tris[2-(Acryloyloxy)Ethyl]Isocyanurate Cross-Linked Polyethylenimine as Antisense Morpholino Oligomer Delivery Vehicle in Cell Culture and Dystrophic mdx Mice 
Human Gene Therapy  2014;25(5):419-427.
Hyperbranched poly(ester amine)s (PEAs) based on tris[2-(acryloyloxy)ethyl]isocyanurate (TAEI) cross-linked low-molecular-weight polyethylenimine (Mw: 0.8k/1.2k/2.0k) have been evaluated for delivering antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in vivo in the dystrophic mdx mouse. The results show that the PEAs constructed with polyethylenimine (PEI) 2.0k (C series) improved PMO delivery more efficiently than those constructed with PEI 0.8k (A series) or 1.2k (B series) in a GFP reporter-based C2C12 mouse myoblast culture system. The highest efficiency of exon-skipping in vitro with the PMO oligonucleotide targeting human dystrophin exon 50 was obtained when the PEA C12 [TAEI-PEI 2.0k (1:2)] was used. Nearly all of the PEAs improved dystrophin expression in mdx mice by local injection with a 2–4-fold increase when compared with PMO alone. Improved transfection efficiency and lower toxicity indicate the potential of the biodegradable PEA polymers as safe and efficient PMO delivery vectors for in vivo applications.
PMCID: PMC4028087  PMID: 24405395
8.  Highly porous non-precious bimetallic electrocatalysts for efficient hydrogen evolution 
Nature Communications  2015;6:6567.
A robust and efficient non-precious metal catalyst for hydrogen evolution reaction is one of the key components for carbon dioxide-free hydrogen production. Here we report that a hierarchical nanoporous copper-titanium bimetallic electrocatalyst is able to produce hydrogen from water under a mild overpotential at more than twice the rate of state-of-the-art carbon-supported platinum catalyst. Although both copper and titanium are known to be poor hydrogen evolution catalysts, the combination of these two elements creates unique copper-copper-titanium hollow sites, which have a hydrogen-binding energy very similar to that of platinum, resulting in an exceptional hydrogen evolution activity. In addition, the hierarchical porosity of the nanoporous copper-titanium catalyst also contributes to its high hydrogen evolution activity, because it provides a large-surface area for electrocatalytic hydrogen evolution, and improves the mass transport properties. Moreover, the catalyst is self-supported, eliminating the overpotential associated with the catalyst/support interface.
Investigations into non-precious metal catalysts for hydrogen evolution are ongoing. Here, the authors report a hierarchical, nanoporous copper-titanium electrocatalyst, and demonstrate that it catalyses hydrogen production at twice the over-all rate of commercial platinum-based catalysts.
PMCID: PMC4382682  PMID: 25910892
9.  PABPC1 exerts carcinogenesis in gastric carcinoma by targeting miR-34c 
As one of the common malignant tumors that threaten human health severely, gastric carcinoma is the second highest cause of cancer death and the fourth most common cancer globally. However, the mechanism underling gastric cancer is still not fully understood. PABPC1 plays an important role in translation, control the rate of mRNA deadenylation and participates in mRNA decay, which is involved in carcinogenesis. Here in present study, we reported that PABPC1 is an oncogenic protein in gastric carcinoma. The results showed that PABPC1 is upregulated in gastric carcinoma tissues, and high PABPC1 expression predicts poor survival. PABPC1 regulates proliferation and transformation of gastric cancer cells in vitro and in vivo. PABPC1 knockdown induces apoptosis by upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins. In addition, miR-34c is a target of PABPC1, and miR-34c is critically essential for the function of PABPC1. In summary, PABPC1 exerts carcinogenesis and promotes growth and survival of gastric cancer cells by regulating miR-34c.
PMCID: PMC4466948  PMID: 26097561
PABPC1; gastric carcinoma; carcinogenesis; miR-34c
10.  Identification of species and materia medica within Angelica L. (Umbelliferae) based on phylogeny inferred from DNA barcodes 
Molecular Ecology Resources  2014;15(2):358-371.
DNA barcodes have been increasingly used in authentication of medicinal plants, while their wide application in materia medica is limited in their accuracy due to incomplete sampling of species and absence of identification for materia medica. In this study, 95 leaf accessions of 23 species (including one variety) and materia medica of three Pharmacopoeia-recorded species of Angelica in China were collected to evaluate the effectiveness of four DNA barcodes (rbcL, matK, trnH-psbA and ITS). Our results showed that ITS provided the best discriminatory power by resolving 17 species as monophyletic lineages without shared alleles and exhibited the largest barcoding gap among the four single barcodes. The phylogenetic analysis of ITS showed that Levisticum officinale and Angelica sinensis were sister taxa, which indicates that L. officinale should be considered as a species of Angelica. The combination of ITS + rbcL + matK + trnH-psbA performed slight better discriminatory power than ITS, recovering 23 species without shared alleles and 19 species as monophyletic clades in ML tree. Authentication of materia medica using ITS revealed that the decoction pieces of A. sinensis and A. biserrata were partially adulterated with those of L. officinale, and the temperature around 80 °C processing A. dahurica decoction pieces obviously reduced the efficiency of PCR and sequencing. The examination of two cultivated varieties of A. dahurica from different localities indicated that the four DNA barcodes are inefficient for discriminating geographical authenticity of conspecific materia medica. This study provides an empirical paradigm in identification of medicinal plants and their materia medica using DNA barcodes.
PMCID: PMC4344822  PMID: 24961287
Angelica; authentication; decoction pieces; DNA barcodes; materia medica
11.  Endemic shrubs in temperate arid and semiarid regions of northern China and their potentials for rangeland restoration 
AoB Plants  2015;7:plv063.
The shrubs Amygdalus pedunculata, Amygdalus mongolica and Ammopiptanthus mongolicus are endemic species in temperate northern China. They have developed adaptations to characteristic arid and semiarid ecosystems. A. pedunculata prefers low hills and sandy land in semiarid regions. A. mongolica prefers gravel deserts in semiarid regions. A. mongolicus prefers sandy land in arid regions. They play critical roles in maintaining or restoring these ecosystems. However, they are in danger of extinction. As part of a general conservation effort, they can be used as nurse plants to facilitate vegetation establishment in the engineering of rangeland restoration.
Some endemic shrubs in arid and semiarid ecosystems are in danger of extinction, and yet they can play useful roles in maintaining or restoring these ecosystems, thus practical efforts are needed to conserve them. The shrubs Amygdalus pedunculata Pall., Amygdalus mongolica (Maxim.) Ricker and Ammopiptanthus mongolicus (Maxim. ex Kom.) Cheng f. are endemic species in arid and semiarid regions of northern China, where rangeland desertification is pronounced due to chronic overgrazing. In this study, we tested the hypothesis that these endemic shrubs have developed adaptations to arid and semiarid environments and could play critical roles as nurse species to initiate the process of rangeland recovery. Based on careful vegetation surveys, we analysed the niches of these species in relation to precipitation, temperature and habitats. All sampling plots were categorized by these endemics and sorted by the non-metric multidimensional scaling method. Species ratios of each life form and species co-occurrence rates with the endemics were also evaluated. Annual average temperature and annual precipitation were found to be the key factors determining vegetation diversity and distributions. Amygdalus pedunculata prefers low hills and sandy land in temperate semiarid regions. Amygdalus mongolica prefers gravel deserts of temperate semiarid regions. Ammopiptanthus mongolicus prefers sandy land of temperate arid regions. Communities of A. pedunculata have the highest diversity and the largest ratios of long-lived grass species, whereas those of A. mongolicus have the lowest diversity but the largest ratios of shrub species. Communities of A. mongolica are a transition between the first two community types. These findings demonstrate that our focal endemic shrubs have evolved adaptations to arid and semiarid conditions, thus they can be nurse plants to stabilize sand ground for vegetation restoration. We suggest that land managers begin using these shrub species to restore degraded rangelands as part of a general conservation effort.
PMCID: PMC4516776  PMID: 26041782
Drought-enduring shrubs; endemic species; northern China; nurse plants; rangeland restoration; sand stabilization; species conservation; temperate arid regions
12.  A Single Chain Variant of Factor VIII Fc Fusion Protein Retains Normal In Vivo Efficacy but Exhibits Altered In Vitro Activity 
PLoS ONE  2014;9(11):e113600.
Recombinant factor VIII Fc (rFVIIIFc) is a fusion protein consisting of a single B-domain-deleted (BDD) FVIII linked recombinantly to the Fc domain of human IgG1 to extend half-life. To determine if rFVIIIFc could be further improved by maintaining the heavy and light chains within a contiguous single chain (SC), we evaluated the activity and function of SC rFVIIIFc, an isoform that is not processed at residue R1648. SC rFVIIIFc showed equivalent activity in a chromogenic assay compared to rFVIIIFc, but approximately 40% activity by the one-stage clotting assay in the presence of von Willebrand Factor (VWF), with full activity in the absence of VWF. Moreover, SC rFVIIIFc demonstrated markedly delayed thrombin-mediated release from VWF, but an activity similar to that of rFVIIIFc upon activation in FXa generation assays. Therefore, the apparent reduction in specific activity in the aPTT assay appears to be primarily due to delayed release of FVIII from VWF. To assess whether stability and activity of SC rFVIIIFc were affected in vivo, a tail vein transection model in Hemophilia A mice was utilized. The results demonstrated similar pharmacokinetic profiles and comparable efficacy for SC rFVIIIFc and rFVIIIFc. Thus, while the single chain configuration did not promote enhanced half-life, it reduced the rate of release of FVIII from VWF required for activation. This impaired release may underlie the observed reduction in the one-stage clotting assay, but does not appear to affect the physiological activity of SC rFVIIIFc.
PMCID: PMC4240654  PMID: 25415306
13.  Gastric wall implantation metastasis of retroperitoneal extraskeletal osteosarcoma: A case report and review of the literature 
Oncology Letters  2014;8(6):2431-2435.
Retroperitoneal extraskeletal osteosarcoma (ESOS) is a rare and highly invasive tumor that is usually diagnosed at an advanced stage due to the insidious onset. The present study analyses a case of retroperitoneal ESOS and its clinical, radiological and therapeutic conditions, and also provides a review of the literature. A 52-year-old male was diagnosed with retroperitoneal ESOS. The patient succumbed to the condition one year after the initial surgery. During treatment, the patient underwent two additional surgeries and two courses of chemotherapy. In the present case, a peritoneal metastatic lesion of ESOS was shed from the peritoneum and implanted into the outer membrane of the stomach and metastasis was identified, this has rarely been reported in the literature. Retroperitoneal ESOS should be considered in the differential diagnosis of a retroperitoneal mass in order to facilitate the management of surgery and help determine the appropriate treatment of the disease.
PMCID: PMC4214496  PMID: 25364404
retroperitoneal extraskeletal osteosarcoma; implantation metastasis; therapy
14.  Impact of oxidative stress on the cytoskeleton of pancreatic epithelial cells 
In the present study the effect of reactive oxygen species on the morphological changes of pancreatic epithelial cells in a three-dimensional culture system was investigated. In addition, the expression of signaling molecules during this process was determined. Matrigel™ was used to construct a three-dimensional culture model of pancreatic epithelial and cancer cells. The cultured cells were stimulated with 1 or 200 μmol/l H2O2 (a typical reactive oxygen species), and the morphological changes were then evaluated after 15 min, 1 h and 4 h. The cytoskeleton of the cells was observed using laser scanning confocal microscopy with immunofluorescence staining. In addition, the nuclear content of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) was detected using ELISA. The results demonstrated that treatment with 200 μmol/l H2O2 induced cell contraction after 15 min, and cell morphology recovered after 1 h; however, cell size was reduced after 4 h. Consequently, intracellular actin and microtubules were rapidly lost following H2O2 treatment, and the cytoskeleton became indistinct and eventually disintegrated after 4 h. Similar observations were noted for the normal pancreatic epithelial and cancer cells. By contrast, treatment with 1 μmol/l H2O2 did not affect the morphology and cytoskeleton of pancreatic epithelial cells. In addition, 200 μmol/l H2O2 treatment increased the activity of NF-κB gradually, while 1 μmol/l H2O2 treatment was found to have little impact on the activity of NF-κB. Therefore, it was demonstrated that oxidative stress can induce the early onset of reversible cell contraction and cytoskeleton depolarization in pancreatic epithelial cells, and can increase NF-κB expression.
PMCID: PMC4186494  PMID: 25289036
pancreatic disease; oxidative stress; nuclear factor κ-light-chain-enhancer of activated B cells
15.  A Renaissance for Antisense Oligonucleotide Drugs in Neurology 
Archives of neurology  2009;66(1):32-38.
Antisense oligonucleotides are short nucleic acid sequences designed for use as small-molecule drugs. They recognize and bind to specific messenger RNA (mRNA) or pre-mRNA sequences to create small double-stranded regions of the target mRNA that alter mRNA splicing patterns or inhibit protein translation. Antisense approaches have been actively pursued as a form of molecular medicine for more than 20 years, but only one has been translated to a marketed drug (intraocular human immunodeficiency virus treatment). Two recent advances foreshadow a change in clinical applications of antisense strategies. First is the development of synthetic DNA analogues that show outstanding stability and sequence specificity yet little or no binding to modulator proteins. Second is the publication of impressive preclinical and clinical data using antisense in an exon-skipping strategy to increase dystrophin production in Duchenne muscular dystrophy. As long-standing barriers are successfully circumvented, attention turns toward scale-up of production, long-term toxicity studies, and the challenges to traditional drug regulatory attitudes presented by tightly targeted sequence-specific drugs.
PMCID: PMC4111150  PMID: 19139297
16.  ChR2 Mutants at L132 and T159 with Improved Operational Light Sensitivity for Vision Restoration 
PLoS ONE  2014;9(6):e98924.
The ectopic expression of microbial opsin-based optogenetic sensors, such as channelrhodopsin-2 (ChR2) in surviving inner retinal neurons, is a promising approach to restoring vision after retinal degeneration. However, a major limitation in using native ChR2 as a light sensor for vision restoration is the low light sensitivity of its expressing cells. Recently, two ChR2 mutations, T159C and L132C, were reported to produce higher photocurrents or have ultra light sensitivity. In this study, we created additional ChR2 mutants at these two sites to search for more light responsive ChR2 forms and evaluate their suitability for vision restoration by examining their light responsive properties in HEK cells and mouse retinal ganglion cells. We found additional ChR2 mutants at these two sites that showed a further increase in current amplitude at low light levels in the cells expressing these mutants, or operational light sensitivity. However, the increase in the operational light sensitivity was correlated with a decrease in temporal kinetics. Therefore, there is a trade-off between operational light sensitivity and temporal resolution for these more light responsive ChR2 mutants. Our results showed that for the two most light responsive mutants, L132C/T159C and L132C/T159S, the required light intensities for generating the threshold spiking activity in retinal ganglion cells were 1.5 and nearly 2 log units lower than wild-type ChR2 (wt-ChR2), respectively. Additionally, their ChR2-mediated spiking activities could follow flicker frequencies up to 20 and 10 Hz, respectively, at light intensities up to 1.5 log units above their threshold levels. Thus, the use of these more light responsive ChR2 mutants could make the optogenetic approach to restoring vision more feasible.
PMCID: PMC4047080  PMID: 24901492
17.  Germplasm preservation in vitro of Polygonum multiflorum Thunb 
Pharmacognosy Magazine  2014;10(38):179-184.
The root of Polygonum multiflorum Thunb. is a common traditional Chinese medicine. In recent years, the wild resources of P. multiflorum have been seriously broken, and the cultivated varieties have been degrading. The germplasm resources of P. multiflorum need protection and preservation. So far, no in vitro germplasm preservation of P. multiflorum has been reported.
To explore a method for the in vitro germplasm preservation of P. multiflorum.
Materials and Methods:
A large number of buds from seed explants were induced by tissue culture. The single buds were used as experimental materials to study the effects of plant growth regulator, temperature, and osmotic pressure on the preservation time, growth recovery, and genetic stability.
When the buds were inoculated onto Murashige and Skoog (MS) basal media containing 4% w/v sucrose, 2% w/v mannitol, and 1% w/v sorbitol, supplemented with paclobutrazol (PP333) 1.0 mg/l, abscisic acid (ABA) 5.0 mg/l, and daminozide (B9) 30.0 mg/l in an illuminated chamber under a 16 h photoperiod of 1500 lx light intensity at 15°C for 10 months, the survival rate was over 70% with good growth recovery and genetic stability.
The results of this study can be used for medium-term in vitro germplasm preservation of P. multiflorum, and meeting actual needs of research and production.
PMCID: PMC4048566  PMID: 24914285
Germplasm; Polygonum multiflorum Thunb.; preservation in vitro
19.  Common variants at CDKAL1 and KLF9 are associated with body mass index in East Asian populations 
Nature genetics  2012;44(3):10.1038/ng.1086.
Obesity is a disorder with complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index (BMI), the most common measure of obesity, have been identified in European populations, few studies have focused on Asian populations. Here, we report a genome-wide association study (GWAS) and replication studies with 62,245 East Asian subjects, which identified two novel BMI-associated loci in the CDKAL1 locus at 6p22 (rs2206734, P = 1.4 × 10−11) and the KLF9 locus at 9q21 (rs11142387, P = 1.3 × 10−9), as well as previously reported loci (the SEC16B, BDNF, FTO, MC4R, and GIPR loci; P < 5.0 × 10−8). We subsequently performed gene–gene interaction analysis and identified an interaction (P = 2.0 × 10−8) between SNPs in the KLF9 locus (rs11142387) and the GDF8 locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity.
PMCID: PMC3838874  PMID: 22344221
20.  Isolation, Purification, Characterization and Effect upon HepG2 Cells of Anemaran from Rhizome Anemarrhena  
The rhizome of Anemarrhena asphodeloides is used as food and traditional Chinese medicine for its hypoglycemic effect. The aim of this study was to investigate the isolation, purification and hypoglycemic activity of Anemaran as the active component. The influence factors (isolation duration, ratio of residuals to water and extracting times) during the isolation process were evaluated. The optimal conditions for NA and AA were extraction temperature 90ºC and 100ºC, duration 1h and 1.5 h, extraction time 3 and 3, and the solid–liquor ratio 1:20 and 1:15, respectively. Neutral and acid Anemaran (NA and AA) were isolated from the rhizome of Anemarrhena asphodeloides. Five fractions of NA-1, NA-2, NA-3, AA-1 and AA-2 were obtained after crude neutral and acid Anemaran purified through DEAE- 52 cellulose anion-exchange column. The characterizations of Anemaran and its different fractions were both analyzed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron micrographs (SEM). Structural properties of different fractions were examined by FT-IR. Strong characteristic absorption peaks were observed at around 1744 cm−1and 1650 cm−1 caused by the C=O group of uronic acids, and the band between 1440 cm−1 and 1395 cm−1 associated with the stretching vibration of C–O of galacturonic acid. Neither the crude neutral, nor the acid anemaran significantly inhibited the growth of HepG2 cells in-vitro, which indicated the low cytotoxicity of the anemaran. Furthermore, both neutral and acid anemaran showed hypoglycemic effect. The hypoglycemic effect of neutral anemaran was much higher than that of acid anemaran.
PMCID: PMC3920721  PMID: 24523758
Anemaran; Isolation; Purification; Characterization; Hypoglycemic effect
21.  Activation of TLR4 is necessary for trauma hemorrhagic shock-induced gut injury and PMN priming 
Shock (Augusta, Ga.)  2012;38(1):107-114.
Interactions of Toll-like receptors (TLR) with non-microbial factors plays a major role in the pathogenesis of early trauma-hemorrhagic shock (T/HS)-induced organ injury and inflammation. Thus, we tested the hypothesis that TLR4 mutant (TLR4mut) mice would be more resistant to T/HS-induced gut injury and neutrophil (PMN) priming than their wild-type (WT) littermates and found that both were significantly reduced in the TLR4mut mice. Additionally, the in vivo and ex vivo PMN priming effect of T/HS intestinal lymph observed in the WT mice was abrogated in TLR4mut mice as well the TRIFmut deficient mice and partially attenuated in Myd88-/- mice suggesting that TRIF activation played a more predominant role than MyD88 in T/HS lymph-induced PMN priming. PMN depletion studies showed that T/HS lymph-induced acute lung injury (ALI) was PMN-dependent, since lung injury was totally abrogated in PMN-depleted animals. Since the lymph samples were sterile and devoid of endotoxin or bacterial DNA, we investigated whether the effects of T/HS lymph was related to endogenous non-microbial TLR4 ligands. HMGB1, heat shock protein (Hsp)-70, Hsp27 and hyaluronic acid, since all have been implicated in ischemia-reperfusion-induced tissue injury. None of these ‘danger’ proteins appeared to be involved, since their levels were similar between the sham and shock lymph samples. In conclusion, TLR4 activation is important in T/HS-induced gut injury and in T/HS lymph-induced PMN priming and lung injury. However, the T/HS-associated effects of TLR4 on gut barrier dysfunction can be uncoupled from the T/HS lymph-associated effects of TLR4 on PMN priming.
PMCID: PMC3378823  PMID: 22575992
mesenteric lymph; shock; MODS; hemorrhage; danger model
22.  Expression of huCdc7 in colorectal cancer 
AIM: To detect the expression of huCdc7 in colorectal cancer.
METHODS: The mRNA and protein expression of huCdc7 in 39 colorectal cancer tissue specimens and matched tumor-adjacent normal colorectal tissue specimens was detected by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively.
RESULTS: The relative expression level of huCdc7 mRNA in colorectal cancer was significantly higher than that in tumor-adjacent normal colorectal tissues (0.03675 ± 1.00 vs 0.01199 ± 0.44, P < 0.05). huCdc7-positive cells displayed brown granules in the nucleus. Tumor tissues contained many huCdc7-positive cells, whereas normal colorectal tissues contained very few positive cells.
CONCLUSION: huCdc7 may play an important role in the development and progression of colorectal cancer.
PMCID: PMC3662954  PMID: 23716994
huCdc7; Semiquantitative reverse transcription-polymerase chain reaction; Colorectal cancer
23.  Brain Responses to Acupuncture Are Probably Dependent on the Brain Functional Status 
In recent years, neuroimaging studies of acupuncture have explored extensive aspects of brain responses to acupuncture in finding its underlying mechanisms. Most of these studies have been performed on healthy adults. Only a few studies have been performed on patients with diseases. Brain responses to acupuncture in patients with the same disease at different pathological stages have not been explored, although it may be more important and helpful in uncovering its underlying mechanisms. In the present study, we used fMRI to compare brain responses to acupuncture in patients with Bell's palsy at different pathological stages with normal controls and found that the brain response to acupuncture varied at different pathological stages of Bell's palsy. The brain response to acupuncture decreased in the early stages, increased in the later stages, and nearly returned to normal in the recovered group. All of the changes in the brain response to acupuncture could be explained as resulting from the changes in the brain functional status. Therefore, we proposed that the brain response to acupuncture is dependent on the brain functional status, while further investigation is needed to provide more evidence in support of this proposition.
PMCID: PMC3662123  PMID: 23737817
24.  Hepatic histopathology and postoperative outcome after preoperative chemotherapy for Chinese patients with colorectal liver metastases 
AIM: To assess the effects of preoperative treatment on the hepatic histology of non-tumoral liver and the postoperative outcome.
METHODS: One hundred and six patients underwent hepatic resection for colorectal metastases between 1999 and 2009. The surgical specimens were reviewed with established criteria for diagnosis and grading of pathological hepatic injury. The impact of preoperative therapy on liver injury and postoperative outcome was analyzed.
RESULTS: Fifty-three patients (50%) received surgery alone, whereas 42 patients (39.6%) received neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%) and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%) had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the perioperative complication rate was not significantly different between the oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated with more steatosis, sinusoidal dilation and steatohepatitis than the surgery group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and mortality (9.1% vs 0% P = 0.02).
CONCLUSION: Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone. However, the preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI can cause pathological changes and tends to increase perioperative morbidity and mortality.
PMCID: PMC3615301  PMID: 23556058
Drug liver injury; Preoperative chemotherapy; Hepatic artery infusion; Sinusoidal dilation
25.  Testosterone depletion / blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph 
The Journal of Trauma  2011;71(6):1652-1658.
We tested the hypothesis that testosterone depletion / blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.
Male, castrated male, or Flutamide-treated rats (25mg/kg sc following resuscitation) were subjected to a laparotomy (trauma), mesenteric lymph duct cannulation and 90 min of shock (35mmHg) or trauma sham-shock. Mesenteric lymph was collected pre, during and post shock. Gut injury was determined at 6 hours post shock using ex vivo ileal permeability with Fluorescein Dextran (FD4). Post-shock mesenteric lymph was assayed for biologic activity in vivo by injection into mice and measuring lung permeability, neutrophil activation and RBC deformability. In vitro neutrophil priming capacity of the lymph was also tested.
Castrated and flutamide-treated male rats were significantly protected against trauma-hemorrhagic shock (T/HS)-induced gut injury as compared to hormonally-intact males. Post-shock mesenteric lymph from male rats had a higher capacity to induce lung injury, PMN activation and loss of RBC deformability when injected into naïve mice as compared to castrated and flutamide treated males. The increase in gut injury after T/HS in males directly correlated with the in vitro biologic activity of mesenteric lymph to prime neutrophils for an increased respiratory burst.
Following T/HS, gut protective effects can be observed in males after testosterone blockade / depletion. This reduced gut injury contributes to decreased biologic activity of mesenteric lymph leading to attenuated systemic inflammation and distant organ injury.
PMCID: PMC3269763  PMID: 22182874
Trauma; Shock; Sex Hormones; Mesenteric Lymph

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