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A nonlocal low-rank regularization approach is proposed for speckle noise removal.A nonconvex surrogate functions for the rank is proposed.We have developed a fast implementation using augmented Lagrange multiplier method.We demonstrate the excellent performance of the technique from PSNR and SSIM. This paper presents a novel method for speckle noise removal. We propose a nonlocal low-rank regularization (NLR) approach toward exploiting structured sparsity and explore its application into speckle noise removal. A nonconvex surrogate functions for the rank instead of the convex nuclear norm is proposed. To further improve the computational efficiency of the proposed algorithm, we have developed a fast implementation using augmented Lagrange multiplier (ALM) method. We experimentally demonstrate the excellent performance of the technique, in terms of both Peak Signal to Noise Ratio (PSNR) and Structural Similarity (SSIM).

Aim of Study: For the tumor lesions close to capsule of the liver, traditional percutaneous radiofrequency ablation (PRFA) is limited due to high incidence of postoperative complications. The aim of the present study is to whether laparoscopic combined with PRFA (LCPR) could effectively ablate the tumor lesions close to capsule of the liver. Methods: A total of 119 patients with subcapsular hepatocellular carcinoma (HCC) were divided into two groups: PRFA group (89 patients) and LCPR group (30 patients). RFA was accomplished through cool-tip RFA system. For LCPR, PRFA was first carried out to destroy tumors deep inside the liver tissue. Then, laparoscopic RFA was performed under the guide of laparoscopic view and destroyed the superficial part of the tumor. Postoperative morbidity and technique effectiveness between two groups were evaluated. Results: In PRFA group, the rate of fever was 70.8% (63/89), and two patients had gallbladder damage. Five patients had ascites. Pain was found in 26 patients (29.2%). In LCPR group, the rate of fever was 22/30 (73.3%). Two patients had ascites and only two patients complained of pain. In PRFA group, 77.5% (69/89) of the tumors were totally ablated, and in LCPR, 93.3% (28/30) of the tumors were destroyed without any residuals. Conclusion: LCPR could significantly reduce the incidence of postoperative pain and the rate of regional tumor residuals compared to the PRFA, suggesting this method could potentially be useful for subcapsular HCC ablation treatment.

Crystal structures, electronic and optical properties of antimony sulfide (Sb2S3) doped by Bi substituting Sb were calculated using a first-principles approach. The effective masses of electrons and holes can be reduced via site-dependent Bi-incorporation, leading to variation of the band dispersion by tuning chemical bond lengths and bond angles. 1.25 at% Bi-doped Sb2S3 shows the optimized optical properties. These theoretical results are in good agreement with experimental observations.

RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG-SeSe-PEI, was developed and its efficacy evaluated. We prepared three mPEG-SeSe-PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG11.6-SeSe-PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG11.6-SeSe-PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG11.6-SeSe-PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).

This article examines the chastity cult in China during the High Qing (c.1680–1830) era. It focuses on the physical characteristics and the cultural implications of chastity arches built in Huizhou (Anhui) during the eighteenth century. Using both written texts and evidence from extant arches, this article explores how these monumental objects served as a forum through which the ideology of female fidelity was constructed and perceived by different constituents including the Manchu court, wealthy Huizhou merchants, and resident commoners. These three groups had different attitudes toward the value of these chastity arches, and thus, this study reveals a dynamic and contradictory picture of how the chastity cult was contested and negotiated in the local community of Huizhou during the late imperial period.

One hallmark of pancreatic cancer (PC) is the high prevalence of pancreatic cancer-associated diabetes mellitus (PC-DM), but the mechanisms remain to be elucidated. Patients with PC who are diagnosed with new-onset diabetes/prediabetes have recently been shown to display significantly lower levels of glucose-dependent insulinotropic peptide (GIP) secreted mainly by enteroendocrine cells. We hypothesized that PC-derived exosomes are responsible for the decreased levels of incretins in patients with PC-DM. In this study, exosomes were successfully isolated from PANC-1, MIA PaCa-2 and SW620 cells and characterized. Only the exosomes from MIA PaCa-2 cells (Exo-Mia) reduce the production of GIP and glucagon-like peptide-1 (GLP-1) from STC-1 cells in vitro in a concentration- and time-dependent manner. Moreover, Exo-Mia increased the levels of the Gip and proglucagon mRNAs and decreased the expression of proprotein convertase subtilisin/kexin type 1/3 (PCSK1/3), which is responsible for the post-translational processing of Gip and proglucagon. Furthermore, differentially expressed exosomal miRNAs (miR-6796-3p, miR-6763-5p, miR-4750-3p and miR-197-3p) were identified and considered to be responsible for the inhibitory effects on GIP and GLP-1 production. To further determine the approach of cancer-derived exosomes reaching enteroendocrine cells, we analyzed the uptake and distribution of exosomes in animal model. It was observed that exosomes infused into the intestinal cavity were more easily internalized by the intestinal epithelium than exosomes injected into blood. In conclusion, pancreatic cancer-derived exosomes (Exo-Mia) suppress the synthesis of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3. Moreover, it may be the pancreatic juice that transport cancer-derived exosomes to target cells (K and L cells) in the gut.

A polyhydroxyalkanoate (PHA)-producing strain was isolated from propylene oxide (PO) saponification wastewater activated sludge and was identified as Brevundimonas vesicularis UJN1 through 16S rDNA sequencing and Biolog microbiological identification. Single-factor and response surface methodology experiments were used to optimize the culture medium and conditions. The optimal C/N ratio was 100/1.04, and the optimal carbon and nitrogen sources were sucrose (10 g/L) and NH4Cl (0.104 g/L) respectively. The optimal culture conditions consisted of initial pH of 6.7 and an incubation temperature of 33.4 °C for 48 h, with 15% inoculum and 100 mL medium at an agitation rate of 180 rpm. The PHA concentration reached 34.1% of the cell dry weight and increased three times compared with that before optimization. The only report of PHA-producing bacteria by Brevundimonas vesicularis showed that the conversion rate of PHAs using glucose as the optimal carbon source was 1.67%. In our research, the conversion rate of PHAs with sucrose as the optimal carbon source was 3.05%, and PHA production using sucrose as the carbon source was much cheaper than that using glucose as the carbon source.

To investigate the effects of siRNAs targeting CD97 immune epitopes on proliferation, infiltration, apoptosis and cell cycle of breast cancer cells.siRNA sequences targeting CD97The growth and proliferation activity of CD97siRNAs-transfected MDA-MB231 cells were significantly lower than those in the control groups, and such differences were more significant in CD97CD97 plays an important role in the cell growth, proliferation, migration and invasion of breast cancer MDA-MB231 cells, and compared with CD97

Autophagy defect has been shown to be correlated with malignant phenotype and poor prognosis of human cancers, however, the detailed mechanisms remain obscure. In this study, we investigated the biological changes induced by autophagy inhibition in gastric cancer. We showed that inhibition of autophagy in gastric cancer cells promotes epithelial-mesenchymal transition (EMT) and metastasis, alters metabolic phenotype from mitochondrial oxidative phosphorylation to aerobic glycolysis and converts cell phenotype toward malignant, which maybe further contribute to chemoresistance and poor prognosis of gastric cancer. We also identified that the EMT and metabolism alterations induced by autophagy inhibition were dependent on ROS-NF-κB-HIF-1α pathway. More importantly, scavenging of ROS by the antioxidant N-acetylcysteine (NAC) attenuated activation of NF-κB and HIF-1α in autophagy-deficient gastric cancer cells, and autophagy inhibition induced metastasis and glycolysis were also diminished by NAC in vivo. Taken together, our findings suggested that autophagy defect promotes metastasis and glycolysis of gastric cancer, and antioxidants could be used to improve disease outcome for gastric cancer patients with autophagy defect.

A series of buta-1,3-dienes have been directly synthesized via a convenient palladium-catalyzed homodehydrogenation coupling reaction of aromatic alkenes under mild conditions. The homocoupling reaction enables a rapid synthesis of multisubstituted butadiene which shows typical aggregation-induced emission enhancement (AIEE) characteristics because it is practically not emissive in solution but emits blue fluorescence in aggregates.

Background It was previously shown that islets are susceptible to oxidative stress due to their inherent low antioxidant capacity. Therefore, in this study, we determined whether treatment of mouse islets with an antioxidant cyanidin-3-O-glucoside (C3G) could enhance their function after transplantation under the kidney capsule or into the portal vein. Methods B6 mouse islets were treated with various concentrations of C3G, their viability, and the expression of antioxidant (HO-1) and antiapoptotic (Bcl-2 and Survivin) genes were determined. The C3G-treated (1.0 μM) or untreated B6 mouse islets (100, 200, and 400 IEQ) were transplanted under the kidney capsule or into the portal vein of diabetic B6 mice, and their blood glucose levels were monitored for more than 100 days after transplantation. Results The C3G-treated islets showed higher cell viability compared to untreated control and the expression of HO-1; Bcl-2 and Survivin genes were enhanced in a concentration-dependent manner. All mice that were transplanted with C3G-treated islets achieved normoglycemia faster than recipients of untreated islets. Mice that received 400, 200, or 100 treated islets transplanted under the kidney capsule achieved normoglycemia, whereas only mice that were transplanted with 400 and 200 treated islets into the portal vein achieved normoglycemia. The mean blood glucose levels of mice that received C3G-treated islets were lower compared to those observed in mouse recipients of untreated islets transplanted under the kidney capsule or into the portal vein. Conclusions Our results show that C3G could enhance the viability of mouse islets and improve their function after transplantation.

Natural image statistics indicate that we should use non-convex norms for most regularization tasks in image processing. Therefore, in order to restore the damaged image better, this paper proposes a new non-convex high variational image inpainting model. An iteratively reweighed minimization method is proposed to tackle this non-convex problem. Experimental results show that the proposed method yields quantitative and qualitative improvements compared to the current Total Variation (TV) method and convex second Total Generalized Variation (TGV) inpainting method.

Prospective epidemiological studies have consistently suggested that pancreatic cancer-associated new-onset diabetes mellitus (PC-DM) represents a potential platform for early diagnose of pancreatic cancer (PC). Despite the studies performed, the mechanism behind this phenomenon remains ambiguous. In this study, we explored the effects of two types of exosomes released by murine pancreatic cancer and ductal epithelial cells on murine skeletal muscle cells. The results show that PC-derived exosomes can readily enter C2C12 myotubes, triggering lipidosis and glucose intake inhibition. We also demonstrate that PC-derived exosomes can inhibit insulin and PI3K/Akt signalling, in which insulin-induced FoxO1 nuclear exclusion is preserved and Glut4 trafficking is impaired. Microarray and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses show that exosomal microRNAs (miRNAs) probably play key roles in this process, an assumption that is corroborated by in vitro studies. These results confirm that the insulin resistance (IR) of skeletal muscle cells is governed by PC-derived exosomes through the insulin and PI3K/Akt/FoxO1 signalling pathways, where exosomal miRNAs potentially contribute to this phenomenon. These novel findings pave the way towards a comprehensive understanding of the cancer theories: “metabolic reprogramming” and “metabolic crosstalk”.

This chapter sets the scene for this study, examining the historical and political reasons for the Huizhou salt merchants’ rise and their connection with the court during the High Qing period. It explains how the Manchu court reformed existing salt monopoly policies by appointing the emperors’ bondservants as salt bureau officials and by establishing the new position of head merchant. These two policies injected the Manchu emperors’ own networks into the salt monopoly institution and allowed the court to effectively exert influence on the wealthiest commercial centers of the Lower Yangzi area. The Huizhou salt merchants, on the other hand, created new and direct ties with the court by obtaining head merchant positions. These merchants thus achieved unprecedented economic and political privileges that took advantage of the Manchu court’s own ethnic strategies.

This chapter discusses merchants’ roles in collecting culture during the High Qing period through a study of the salt merchant Wang Qishu and his collection of seals. The Qianlong emperor’s personal interest in collecting and his compilation of a large series of court-sponsored catalogues led to a recognition of collectors in Qing society. Collectors (shoucangjia) emerged as a unique social category, and collecting came to be seen as a valued form of expertise. By locating Wang Qishu’s case in this High Qing context, the author examines how Wang used different elements associated with his seal collection to assert himself as a collector. Wang’s contemporaries also saw him as a collector passionate about seals, as an expert in seal connoisseurship, and as financially capable of amassing a distinguished collection. Through his collection, Wang assumed the role of “collector”—a new social status symbol—and thereby legitimized his position in society.

The introduction presents the Huizhou salt merchants, with emphasis on the unprecedented economic and political privileges they enjoyed in High Qing China. The author challenges the conventional analysis focused on merchant-literati status negotiations, arguing that this framework is based upon written texts produced by the literati themselves, and is hence not reflective of the merchants’ own concerns. By reviewing the extant literary descriptions of Huizhou salt merchants, the author proposes to explore their own voices and opinions by analyzing their interactions with material objects. This indicates the emergence of a novel and vital network between the Qianlong emperor, the imperial household department, court officials, and Huizhou salt merchants, constructed between the capital Beijing, the urban centers of Jiangnan, and the remote countryside of Huizhou. A focus on these salt merchants sheds new light on Manchu emperors’ political strategies and reveals merchants’ role in luxury consumption in High Qing China.

This chapter examines the salt merchants’ role in constructing chastity arches—stone structures honoring women who maintained chaste widowhood—in She county in Huizhou. In the High Qing era, the Manchu court systematically patronized the construction of monumental objects, such as stone arches, with the dual object of inculcating Confucian morality in their illiterate subjects and displaying their imperial legitimacy. The Huizhou salt merchants, seeing an opportunity to expand their influence, devoted themselves to chastity arch construction in the local community of Huizhou, thus publicizing the virtuous deeds that the court rewarded. While these merchants used their economic prowess to participate in the state’s cultivation project, their financial support of these arches was itself a product of the court’s salt monopoly policies. At the same time, these monuments gave these wealthy businessmen the opportunity to bolster their reputations, display their wealth, and lay claim to legitimate dominance in local society.

This book explores the transformation of Huizhou salt merchants’ social and political status in eighteenth-century China. These merchants left their homes in the remote countryside of Huizhou, conducting business and sojourning in the most prosperous part of the Qing empire (1644-1911), the Lower Yangzi valley. Benefiting from the new salt monopoly policies instituted by Manchu emperors, they became one of the wealthiest merchant groups of the High Qing period (1683-1839).

Chapter 2 examines the Huizhou head merchants’ interaction with the most precious and expensive goods in eighteenth-century Jiangnan. It explores how these businessmen produced and procured objects for imperial use through the tribute system, manufacturing, and the Qianlong emperor’s empire-wide book collecting project. This chapter shows in detail how the Huizhou salt merchants procured objects from local workshops, markets, and private collections and how their personal networks and managerial ability enabled them to “run errands” for the court. While the salt merchants supplemented formal state bureaucratic systems and served as the emperor’s informal agents in Jiangnan, they also facilitated an exchange of style and taste between the capital and Jiangnan.

This chapter takes the case of the Bao family from Tangyue village to explore the ways in which salt merchants patronized lineage construction projects as a means to expand the influences of their families in the countryside of Huizhou and to strengthen a connection with urban scholarly elites. By tracing the construction process of three lineage projects sponsored by the Bao household—the publishing of a new genealogy, the construction of a shrine, and the donation of charitable lands—the author shows how the Bao merchants patronized specific lineage construction projects, which functioned as luxury items sanctioned by Confucian moral example. Through these cultural objects, the Bao family expanded their influence in their rural homeland in Huizhou, and displayed their moral values for the benefit of scholarly elites in the court and Jiangnan urban centers, creating connections between the countryside and the city, and the central and local.

The conclusion argues that the Huizhou salt merchants emerged as “cultured and cosmopolitan men” who distinguished themselves with knowledge and skill in a wide range of fields, being famed for their managerial prowess. Through their production and consumption of a variety of objects, these merchants played multiple roles in the fluid material world of High Qing China, whether as the emperor’s informal agents or arbiters of taste, lineage patrons or moral advocates. By playing these roles, these salt merchants also constructed a dynamic and fluid urban-rural and central-local relationship in the high Qing period. Study of these salt merchants thus sheds new light on the Qianlong emperor’s political strategy in Jiangnan and reveals the differences and transformations of consumer cultures in China from the late Ming to the high Qing.

Drug-resistance to gemcitabine chemotherapy in pancreatic cancer is still an unsolved problem. Combinations of other chemotherapy drugs with gemcitabine have been shown to increase the efficacy of gemcitabine-based treatment. In this study, the effect of berbamine on the antitumor activity of gemcitabine was evaluated in human pancreatic cancer cell lines Bxpc-3 and Panc-1, and the underlying mechanisms were explored. Our results demonstrated that berbamine exhibited a time- and dose-dependent inhibitory effect in the pancreatic cancer cell lines. Berbamine enhanced gemcitabine-induced cell growth inhibition and apoptosis in these cells. Combined treatment of berbamine and gemcitabine resulted in down-regulation of anti-apoptotic proteins (Bcl-2, Bcl-xL) and up-regulation of pro-apoptotic proteins (Bax, Bid). More importantly, berbamine treatment in combination with gemcitabine activated the transforming growth factor-β/Smad (TGF-β/Smad) signaling pathway, as a result of a decrease in Smad7 and an increase in transforming growth factor-β receptor II (TβRII) expression. Changes in downstream targets of Smad7, such as up-regulation of p21 and down-regulation of c-Myc and Cyclin D1 were also observed. Therefore, berbamine could enhance the antitumor activity of gemcitabine by inhibiting cell growth and inducing apoptosis, possibly through the regulation of the expression of apoptosis-related proteins and the activation of TGF-β/Smad signaling pathway. Our study indicates that berbamine may be a promising candidate to be used in combination with gemcitabine for pancreatic cancer treatment.

Aims A lack of explicit information on differential controls on net primary productivity (NPP) across regions and ecosystem types is largely responsible for uncertainties in global trajectories of terrestrial carbon balance with changing environment. The objectives of this study were to determine how NPP of different forest types would respond to inter-annual variability of climate and to examine the responses of NPP to future climate change scenarios across contrasting forest types in northern China. Methods We investigated inter-annual variations of NPP in relation to climate variability across three forest types in northern China, including a boreal forest dominated by Larix gmelinii Rupr., and two temper ate forests dominated by Pinus tabulaeformis Carr. and Quercus wutaishanica Mayr., respectively, and studied the responses of NPP in these forests to predicted changes in climate for the periods 2011–40, 2041–70 and 2070–100 under carbon emission scenar ios A2 and B2 of Intergovernmental Panel on Climate Change. We simulated the responses of NPP to predicted changes in future climate as well as inter-annual variability of the present climate with the Biome-BGC version 4.2 based on site- and species-specific parameters. The modeled forest NPP data were validated against values in literature for similar types of forests and compared with inter-annual growth variations reflected by tree-ring width index (RWI) at the study sites. Important Findings Inter-annual variations in modeled NPP during the period 1960–06 were mostly consistent with the temporal patterns in RWI. There were contrasting responses of modeled NPP among the three forest types to inter-annual variability of the present climate as well as to predicted changes in future climate. The modeled NPP was positively related to annual mean air temperature in the L. gmelinii forest (P

Islet replacement is a promising cure for insulin-dependent diabetes but is limited by a massive early cell death following transplantation. Overburden oxidative stress is one of the major factors causing cell damage. We have shown previously that anthocyanins in Chinese bayberry extract protected β cells (INS-1) from hydrogen peroxide (H₂O₂)-induced apoptosis and decreased grafts' apoptosis after transplantation partially through heme oxygenase-1 (HO-1) up-regulation. In the present study, we observed that H₂O₂ stimulation induced autophagy in β cells. Inhibition of autophagy increased cell viability and decreased cell death. Anthocyanin pretreatment attenuated oxidative stress-mediated autophagic cell death. Anthocyanins activated antioxidant transcription factor Nrf2 in INS-1 cells, and Nrf2/HO-1 negatively regulated autophagy process. Furthermore, we here demonstrate that autophagy also took place in β cell grafts during the early post-transplantation phase. β Cells pretreated with anthocyanins displayed decreased extent of autophagy after transplantation. Taken together, these findings further supported the conclusion that anthocyanins could serve as a protective agent of β cells and suggested that autophagy might play a role in β cells during transplantation.

Noninvasive targeted visualization of pancreatic beta cells or islets is becoming the focus of molecular imaging application in diabetes and islet transplantation studies, but it is currently unsuccessful due to the lack of specific beta cell biomarkers. Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in beta cells and considered as a promising target. We here developed a targeted superparamagnetic iron oxide (SPIO) nanoparticle using GLP-1 analog-exendin-4 which is conjugated to polyethylene glycol coated SPIO (PEG-SPIO). The results demonstrated that exendin-4 functionalized SPIO was able to specifically bind to and internalized by GLP-1R-expressing INS-1 cells, with the higher labeling efficiency than non-targeted nanoparticles. Notably, SPIO-exendin4 could differentially label islets in pancreatic slices or beta cell grafts in vitro. Systemic delivery of SPIO-exendin4 into nude mice bearing s.c. insulinomas (derived from INS-1 cells) leads to the accumulation of the nanoparticles in tumors, generating a strong magnetic resonance imaging contrast detectable by a clinical MRI scanner at field strength of 3.0 T, and the iron deposition in tumors was further confirmed by Prussian blue staining. Furthermore, preliminary biodistribution study indicated that SPIO-exendin4 had a tendency to accumulate in pancreas. Toxicity assessments demonstrated good biocompatibility in vivo. These results suggest that SPIO-exendin4 has potential as molecularly targeted imaging agents for in vivo imaging of insulinoma, and possibly for future beta cell imaging.

The stubborn chemoresistance of pancreatic ductal adenocarcinoma (PDA) is simultaneously influenced by tumor parenchymal and stromal factors, and the ctritical role of Notch ligand Delta-like 4 (DLL4) in the regulation of tumor malignancies has been observed. DLL4 positive expression ratio between duct cells from clinical tumor and adjacent tissues was statistically significant, and the overactivation of DLL4/Notch pathway enhanced the phenotype of EMT and cancer stem cell, even can induce multi-chemoresistance in vitro. Notably, the accompanied defective angiogenesis directly induced inefficient chemo-drug delivery in vivo. Collectively, overexpressed DLL4 on neoplastic cells can enhance chemoresistance through angiogenesis-dependent/independent mechanisms in PDA.

Background The aim of this study is to assess the validity of the measurement of pepsinogen as a screening test for chronic atrophic gastritis (AG) in health check-up populations in China. Methods Patients from consecutive regular health check-up were enrolled from January 2014 to June 2015. Endoscopy, combined with monitoring the Helicobacter pylori (Hp) infections, and measuring the serum pepsinogen (PG) were used to determine the diagnostic accuracy of PG for the screening of atrophic gastritis. Histopathology was assessed by the Operative Link on Gastritis Assessment (OLGA) system. Statistical analysis was performed using SPSS statistical software. Results The total Hp infection rate was 40%. Based on pathology, the 996 participants were divided into three groups: non-atrophic (NAG), mild-moderate atrophic (MAG): stage I and II of the OLGA classification, and severe atrophic (SAG): stage III and IV of the OLGA classification. Compared with NAG and MAG groups, PGR decreased significantly in SAG group (p

Background Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Among the surgical and nonsurgical treatments available, radiofrequency ablation (RFA) and sorafenib have been shown to have efficacy. There is little evidence whether combination of these therapies would have additional benefits. Methods In a mouse model of HCC, effects of sorafenib were determined by tumor size, RFA-induced necrosis area (triphenyltetrazolium chloride staining), microvascular density (MVD; 4’,6-diamidino-2-phenylindole and anti-CD31 antibody staining), and tumor perfusion (magnetic resonance imaging). Results The RFA-induced necrosis area was 80.98 ± 9.14 and 69.49 ± 7.46 mm2 in mice administered 80 and 40 mg/kg sorafenib, respectively, but only 57.29 ± 3.39 mm2 in controls. Sorafenib also reduced tumor volume and enhanced RFA-induced tumor destruction in a dose-dependent manner, and reduced both MVD and tumor perfusion. Conclusions The results of our study suggest a potential role for combining RFA with sorafenib for treatment of HCC. Sorafenib could enhance RFA efficiency, possibly through its angiogenesis suppressive effects.

RNA interference (RNAi)-mediated gene therapy is a promising approach to cure various diseases. However, developing an effective, safe, specific RNAi delivery system remains a major challenge. In this study, a novel redox-responsive polyetherimide (PEI)-based nanovector, mPEG-SeSe-PEI, was developed and its efficacy evaluated. We prepared three mPEG-SeSe-PEI vector candidates for small interfering glyceraldehyde-3-phosphate dehydrogenase (siGADPH) and determined their physiochemical properties and transfection efficiency using flow cytometry and PEG11.6-SeSe-PEI polymer. We investigated the silencing efficacy of GADPH mRNA expression in PANC-1 cells and observed that PEG11.6-SeSe-PEI/siGADPH (N/P ratio=10) polyplexes possessed the appropriate size and zeta-potential and exhibited excellent in vitro gene silencing effects with the least cytotoxicity in PANC-1 cells. In conclusion, we present PEG11.6-SeSe-PEI as a potential therapeutic gene delivery system for small interfering RNA (siRNA).

Objective: To define the roles of gray-scale, color-Doppler ultrasound, and sonoelastography for the assessment of thyroid nodule to determine whether nodule size affects the differential diagnosis of benign and malignant. Methods: A total of 243 consecutive subjects (214 women, 29 men) with 329 thyroid nodules were examined by gray-scale, color-Doppler ultrasound, and sonoelastography in this prospective study. All patients underwent surgery and the final diagnosis was obtained from histopathological examination. Results: Three hundred and twenty-nine nodules (208 benign, 121 malignant) were divided into small (SNs, 5–10 mm, n=137) and large (LNs, >10 mm, n=192) nodules. Microcalcifications were more frequent in malignant LNs than in malignant SNs, but showed no significant difference between benign LNs and SNs. Poorly-circumscribed margins were not significantly different between malignant SNs and LNs, but were less frequent in benign LNs than in benign SNs. Among all nodules, marked intranodular vascularity was more frequent in LNs than in SNs. By comparison, shape ratio of anteroposterior to transverse dimensions (A/T) ≥1 was less frequent in LNs than in SNs. Otherwise, among all nodules, marked hypoechogenicity and elasticity score of 4–6 showed no significant difference between LNs and SNs. Conclusions: The predictive values of microcalcifications, nodular margins, A/T ratio, and marked intranodular vascularity depend on nodule size, but the predictive values of echogenicity and elastography do not.

It has been suggested that the newly identified metastasis-associated in colon cancer-1 (MACC1) oncogene is involved in the progression and metastasis of cancer. Several studies have indicated that MACC1 has potential as a novel biomarker. In this study, we aimed to investigate the functions and serum expression levels of MACC1 in pancreatic cancer patients. Blood serum samples from 60 cancer patients and 49 controls were analyzed for serum MACC1 by ELISA. The results revealed that high expression levels of MACC1 were correlated with lymph node metastasis, distant metastasis and a later TNM stage. Inhibition of MACC1 by siRNAs significantly suppressed pancreatic cancer cell proliferation and migration. Furthermore, it was found that the downregulation of MACC1 sensitized pancreatic cancer cells to gemcitabine treatment through the inhibition of the Ras/ERK signaling pathway. Our findings suggest that MACC1 may aid in the diagnosis of pancreatic cancer and serve as a potential therapeutic target.

Aberrant expression of DJ-1 has been proven to be associated with tumorigenesis in many carcinomas. However, its role in pancreatic cancer is unknown. The aims of this study were to investigate whether the serum DJ-1 might be a potential biomarker for pancreatic cancer and to determine the biologic function of DJ-1 expression in gemcitabine-induced chemoresistance of pancreatic cancer. The serum level of DJ-1 was higher in 128 pancreatic cancer patients compared with 62 healthy controls by ELISA. To determine the effect of DJ-1 on pancreatic tumor chemoresistance, a siRNA-targeting DJ-1 was synthesized and a stably transfected cell line with DJ-1 over-expression was constructed. The mechanism of tumor chemoresistance was assessed by multiple methods, such as MTT assay, real-time PCR, Western blot and flow cytometry. The serum level of DJ-1 was higher in pancreatic cancer patients than healthy controls, and it has the relationship with tumor differentiation in pancreatic cancer. Down-regulation of DJ-1 enhanced gemcitabine-induced apoptosis in three pancreatic cancer cell lines. On the contrary, over-expression of DJ-1 desensitized the MIA PaCa-2 to the induction of apoptosis by gemcitabine. Our results suggest that the serum level of DJ-1 may be a potential biomarker for pancreatic cancer, and that DJ-1 plays critical roles in the pancreatic tumor chemoresistance, supporting the development of chemotherapeutic approaches targeting this oncogene.

Islets can be visualized on MRI by labeling with superparamagnetic contrast agent during the transplantation procedure. However, whether the signal intensity reflects the cell number and cellular viability has not been determined. We used a self-synthesized novel superparamagnetic contrast agent –polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) – to label β-TC-6 cells (a mouse insulinoma cell line) or primary islets with commercial Feridex as a control. The labeling efficiency of two agents was compared by Prussian blue staining, intracellular iron content determination and MR scanning. Cells were exposed to hypoxia, high-glucose or exogenous H2O2 stimulation before/after PVP-SPIO labeling. Normal and injured cells were also transplanted into renal subcapsule. A clinically used 3.0 T MR scan was performed in vitro and 24 h post-transplantation to investigate the correlation between cellular viability and signal. Our PVP-SPIO displayed superior biocompatibility and magnetic properties. All of the cells could be labeled at 100 µg/ml iron concentration after 24 h incubation. At 100 µg/ml iron concentration, 1 × 105β cells labeled with PVP-SPIO could already be visualized in vitro by MRI, less than the detection threshold of Feridex. There existed a linear correlation between the number of labeled cells and R2 value on the T2-weighted images. The signal intensity and the intracellular iron content declined along with the decreased viability of labeled cells. There was also a significant difference in signal intensity between injured and normal labeled cells after transplantation. From these results, we concluded that PVP-SPIO possessed superior cell labeling efficiency, and β cells could be labeled without compromising viability and function. The signal intensity on MRI might be a useful predictor to evaluate the number and the viability of PVP-SPIO-labeled cells. Copyright © 2012 John Wiley & Sons, Ltd.

A series of buta-1,3-dienes have been directly synthesized via a convenient palladium-catalyzed homodehydrogenation coupling reaction of aromatic alkenes under mild conditions. The homocoupling reaction enables a rapid synthesis of multisubstituted butadiene which shows typical aggregation-induced emission enhancement (AIEE) characteristics because it is practically not emissive in solution but emits blue fluorescence in aggregates.

BACKGROUND/AIMS To identify potential new tumor markers in peripheral blood mononuclear cells for pancreatic adenocarcinoma screening. METHODOLOGY The total mRNA was extracted from the peripheral blood mononuclear cell samples of both pancreatic adenocarcinoma patients (n=5) and healthy donors (n=5). Having the RNA expression profiling of over 38500 genes via the Human Genome U133 Plus 2.0 Array performed in order to identify differentially expressed genes, the study underwent real-time Reverse Transcriptase PCR (RT-PCR) for validation. RESULTS The mRNA expression profiles identified the Olfactomedin4 gene, which was significantly overexpressed (4.46-fold) versus the control group (p

Aim: To evaluate the feasibility and safety of ultrasound-guided radiofrequency ablation (RFA) of hepatic tumors in high-risk areas (in caudate lobe, adjacent to the hilum, capsular surface, gallbladder or diaphragm) in comparison with those in low-risk areas. Methods: A total of 526 patients with hepatic tumor treated with ultrasound-guided cool-tip RFA between October 2001 and October 2008 were included. The patients were divided into two groups according to the tumor location: group I (high-risk areas, 163 patients); group II (low-risk areas, 363 patients). The two groups had similar baseline characteristics. Repeated RFA was adopted if complete ablation (CA) was not achieved. Results: In group I, 20 cases had tumors close to the hilum, 11 in the caudate, 79 adjacent to the capsule, 24 near the gallbladder and 29 cases against the diaphragm. The percentage of patients with primary hepatic tumors in group I was higher than that in group 2 (80.4% vs 56.2%, P

A simple approach has been developed to synthesize lanthanide based multifunctional magnetic-fluorescent hydrogels for cellular imaging via MRI and optical imaging synchronously. The multifunctional hydrogels are prepared by covalently conjugating gadolinium and europium chelate with biocompatible chitosan. The room temperature photoluminescence (PL) spectrum shows that the hydrogels have a strong PL emission, which is characteristic of Eu3+ transitions from the excited 5D0 to 7FJ levels. Moreover, in vitro magnetic resonance imaging (MRI) analysis shows that the hydrogels exhibit powerful T1-weighted MRI signal in water. As a result, the hydrogels combine magnetic and fluorescent properties and can be expected to act as a promising multimodal MRI/optical imaging probe.

Objectives The purposes of this study were to validate the value of the International Study Group on Pancreatic Fistula (ISGPF) classification scheme for pancreatic fistula (PF) and to identify predictive factors for clinically significant PF. Methods From January 2000 to December 2007, 294 consecutive patients underwent pancreaticoduodenectomy in a single medical center. Pancreatic fistula was evaluated by the ISGPF criteria and Johns Hopkins Hospital's definition (JHH). Then, logistic regression analysis was performed to identify predictive factors for PF development. Our own management strategies with PF were also discussed. Results The overall incidence of PF was 19.4% (57/294) according to the ISGPF criteria, and 8.8% (26/294) using the JHH definition. Thirty-one patients with PF classified by the ISGPF were missed by the JHH definition. By logistic regression analysis, we found that besides the lack of cardiovascular disease and malignant diseases, our single-layer continuous circular invaginated pancreaticojejunostomy was another independent factor for the lowered incidence of PF. Conclusions The ISGPF classification scheme was accurate for evaluating PF. Single-layer continuous circular invaginated pancreaticojejunostomy may be a promising method that may have been responsible for the lower incidence of PF in this study.

Oxidative stress plays a pivotal role during the islet transplantation procedure, and antioxidant supplementation may protect grafts against oxidative injury. Chinese bayberry is one of six Myrica species native to China, and we demonstrated here that anthocyanins from Chinese bayberry extract (CBE) protect pancreatic β cells (INS-1) against hydrogen peroxide (H(2)O(2))-induced necrosis and apoptosis. Anthocyanins time- and dose-dependently upregulated heme oxygenase-1 (HO-1) gene expression in β cells and primary islets. HO-1 knockdown increased H(2)O(2)-induced cell death and attenuated the cytoprotective effect of anthocyanins. Anthocyanin treatment activated ERK1/2 and PI3K/Akt signaling, and ERK1/2 and PI3K inhibitors partially attenuated anthocyanin-mediated induction of HO-1. Additionally, β cells pretreated with anthocyanins displayed a decreased extent of apoptosis after transplantation. In summary, these results suggest that anthocyanins in CBE protect β cells from H(2)O(2)-induced cell injury via ERK1/2- and PI3K/Akt-mediated HO-1 upregulation.

Introduction Severe acute pancreatitis is a life threatening disease with a high rate of mortality, and its treatments are still controversial. The purpose of this study is to investigate the potential effects of proteasome inhibitor PS-341 on severe acute pancreatitis induced by cerulein and lipopolysaccharide in mice. Materials and Methods Severe acute pancreatitis was induced by seven intraperitoneal injections of 50 ug/kg cerulein at hourly intervals and one injection of 10mg/kg lipopolysaccharide in mice. Thirty min before the administration of lipopolysaccharide, mice were treated either with PS-341 or vehicle. The severity of acute pancreatitis was then evaluated by serum and pancreatic biochemical assays as well as histologic examination. Positron emission tomography (PET) was used for the first time to determine the therapeutic effects of interventions in situ. Results PS-341 significantly inhibited NF-κB activation, while the pancreatic cell apoptosis was significantly enhanced, resulting in the improved parameters such as serum amylase, C-reactive protein, lactate dehydrogenase, interleukin-1β, interleukin-6, and pancreatic myeloperoxidase activity. Accordingly, pancreatic damage, including inflammatory cell infiltration, hemorrhage, and necrosis, was markedly reduced. 18F-fluorodeoxyglucose-positron emission tomography demonstrated that PS-341 significantly reduced the uptake of 18F-fluorodeoxyglucose within the pancreas. Conclusions These observations demonstrate that PS-341 was able to significantly reduce the severity of acute pancreatitis induced by cerulein and lipopolysaccharide in mice. The potential effect is associated with the inhibition of NF-κB activation and increased pancreatic cell apoptosis within the pancreas. 18F-fluorodeoxyglucose-positron emission tomography could be a sensitive and promising means in evaluating the therapeutic effect and adjusting medical interventions for pancreatitis.

Extragonadal yolk sac tumor (YST) is a relatively rare entity. We describe here the case of an extragonadal YST that occurred in the pancreas with hepatic metastasis in an adult woman. The contrast enhanced CT images of the abdomen revealed a heterogeneous, solitary mass occupying the pancreatic neck and body with slightly inhomogeneous contrast enhancement. Two low-density lesions in the liver were also displayed on the CT images. The patient underwent surgery and the diagnosis of YST was pathologically verified.

Somatostatinoma is a very rare neuroendocrine tumor that originates from D cells and accounts for less than 1% of all gastrointestinal endocrine tumors. The duodenum is the most frequent site for this tumor, followed by the pancreas. We here describe a 46-year-old Chinese woman who developed pancreatic somatostatinoma presenting with the characteristic “inhibitory” syndrome, but the symptoms were obscure and seemingly uncorrelated. This case is also unique for its large tumor size and mixed pathological pattern. Distal pancreatectomy was performed, and the patient has remained well since operation. As the syndromes of somatostatinoma may be obscure and atypical, clinicians should review all clinical findings to obtain an accurate diagnosis. Aggressive surgery is preferred to improve the survival.

It was recently reported that pluripotent mesenchymal stem cells (MSCs) in rodent bone marrow (BM) have the capacity to generate insulin-producing cells (IPCs) in vitro. However, little is known about this capacity in human BM-MSCs. We developed a nongenetic method to induce human BM-MSCs to transdifferentiate into IPCs both phenotypically and functionally. BM-MSCs from 12 human donors were sequentially cultured in specially defined conditions. Their differentiation extent toward beta-cell phenotype was evaluated systemically. Specifically, after induction human BM-MSCs formed spheroid islet-like clusters containing IPCs, which was further confirmed by dithizone (DTZ) staining and electron microscopy. These IPCs expressed multiple genes related to the development or function of pancreatic beta cells (including NKX6.1, ISL-1, Beta2/Neurod, Glut2, Pax6, nestin, PDX-1, ngn3, insulin and glucagon). The coexpression of insulin and c-peptide was observed in IPCs by immunofluorescence. Moreover, they were able to release insulin in a glucose-dependent manner and ameliorate the diabetic conditions of streptozotocin (STZ)-treated nude mice. These results indicate that human BM-MSCs might be an available candidate to overcome limitations of islet transplantation.

Background: A soluble decoy receptor 3 (DcR3), also known as TR6 or M68, is a member of the TNF receptor family. It has been reported that high DcR3 expression occurs in many tumors. Methods: This prospective study evaluated the DcR3 tissue status by RT-PCR and its correlation with the lymph node (N) stages in 62 primary gastric cancers. Results: DcR3 expression levels in patients with pN2-3 disease were much higher than those in patients with pNO-1 disease (median values 1.31 vs. 0, P < 0.01). Using ROC analysis, a cutoff level of DcR3 expression at 1.20 was found to be associated with optimal sensitivity and specificity of 62.5% (15 of 24) and 92.1% (35 of 38) respectively, in the prediction of stage pN2-3. According to the cutoff value, patients were divided into 2 groups with relatively high and low levels of DcR3 expression. Among the 18 patients with high DcR3 expression, 83.3% (15 of 18) were staged as pN2-3. In the other 44 patients with low DcR3 expression, only 20.5% (9 of 44) were identified as pN2-3. Logistic regression analysis for stage pN2-3 revealed that high DcR3 expression was an independent risk factor. Conclusion: Gastric cancer patients with high DcR3 expression presented more advanced pN2-3 disease than those with low DcR3 expression. Preoperative checking DcR3 expression might be an additional approach to imaging modalities for evaluating N stages in gastric cancer to guide the operative procedures.

Objectives: To evaluate the clinical significance of high-volume modified continuous closed and/or open lavage for the treatment of infected necrotizing pancreatitis. Methods: From August 1997 to December 2006, 53 patients with infected necrotizing pancreatitis who underwent in situ high-volume (>20 L/d) continuous closed lavage using a single-lumen rubber catheter and/or open lavage were retrospectively studied in our hospital, and the advantages of this new technique were analyzed. Results: Modified continuous closed lavage was the initial treatment for all patients; in 6 patients with secondary retroperitoneal sepsis or abscess, continuous open lavage was performed. Impaired tube patency and lavage fluid retention did not occur in any of these patients. The overall mortality was 17.0% (9/53). Twelve patients underwent early surgery, and 5 (41.7%) died; 41 patients underwent delayed surgery, and 4 (9.8%) died. Significant local complications occurred in 14 patients (26.4%); the incidence of bleeding, abscess, and fistula was 13.2% (7/53), 9.4% (5/53), and 9.4% (5/53), respectively. Conclusions: Our technique of in situ high-volume modified continuous closed and/or open lavage has produced a better control of infected necrotizing pancreatitis.

Background In Appleby's operation, the adequate flow of proper hepatic artery (PHA) from pancreaticoduodenal arcades was considered to be important in the previous reported pancreatic cancer cases. Insufficient blood flow of PHA was considered as the contraindication for Appleby's operation. Methods We herein reported a 20 cm in diameter pancreatic sarcomatoid carcinoma involving celiac axis (CA), which was treated by extended Appleby's operation without proper hepatic arterial flow. The extended Appleby's operation for pancreatic cancer involving CA and/or common hepatic artery (CHA) was firstly applied to the current case according to the 43 previous reported cases in English literature from a Medline search. In the extended Appleby's operation, the resection scope included total pancreas, total stomach, spleen, and CA; the anterior and posterior pancreaticoduodenal arcades were removed in whipple's procedure, which was previously thought to be the contraindication for Applyby's operation. Results Proper hepatic arterial flow from superior mesenteric artery (SMA) was totally lost; No liver failure happened postoperatively. Conclusions The extended Appleby's procedure without blood flow of PHA might be feasible and offered a new approach to resection of pancreatic cancer involving CA and/or CHA; the involvement of pancreatic head might not be the contraindication for Appleby's operation. J. Surg. Oncol. 2007;96:442–446. © 2007 Wiley-Liss, Inc.