Publications by authors named "Wentao Gao"

89 Publications

Cancer-Specific Targeting of Taurine-Upregulated Gene 1 Enhances the Effects of Chemotherapy in Pancreatic Cancer.

Cancer Res 2021 Mar 1. Epub 2021 Mar 1.

Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Overcoming drug resistance is one of the biggest challenges in cancer chemotherapy. In this study, we examine whether targeting the long noncoding RNA taurine upregulated gene 1 () could be an effective therapeutic approach to overcome drug resistance in pancreatic ductal adenocarcinoma (PDAC). was expressed at significantly higher levels across 197 PDAC tissues compared with normal pancreatic tissues. Overall survival of patients with PDAC who had undergone 5-FU-based chemotherapy was shorter in high group than in low group. Mechanistically, antagonized miR-376b-3p and upregulated dihydropyrimidine dehydrogenase (DPD). depletion induced susceptibility to 5-FU in BxPC-3 and PK-9 pancreatic cell lines. Consistently, the cellular concentration of 5-FU was significantly higher under -depleted conditions. In PDAC xenograft models, intravenous treatment with a cancer-specific drug delivery system (-DDS) and 5-FU significantly suppressed PDAC tumor growth compared with 5-FU treatment alone. This novel approach using -DDS in combination with 5-FU may serve as an effective therapeutic option to attenuate DPD activity and meet appropriate 5-FU dosage requirements in targeted PDAC cells, which can reduce the systemic adverse effects of chemotherapy. SIGNIFICANCE: Targeting coupled with a cancer-specific drug delivery system effectively modulates 5-FU catabolism in -overexpressing PDAC cells, thus contributing to a new combinatorial strategy for cancer treatment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/00/0/000/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3021DOI Listing
March 2021

Correlation between radiologic features on contrast-enhanced CT and pathological tumor grades in pancreatic neuroendocrine neoplasms.

J Biomed Res 2020 Aug 21:1-10. Epub 2020 Aug 21.

Pancreas Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. E-mail:

Contrast-enhanced computed tomography (CT) contributes to the increasing detection of pancreatic neuroendocrine neoplasms (PNENs). Nevertheless, its value for differentiating pathological tumor grades is not well recognized. In this report, we have conducted a retrospective study on the relationship between the 2017 World Health Organization (WHO) classification and CT imaging features in 94 patients. Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2, including tumor size, shape, margin, heterogeneity, intratumoral blood vessels, vascular invasion, enhancement pattern in both contrast phases, enhancement degree in both phases, tumor-to-pancreas contrast ratio in both phases, common bile duct dilatation, lymph node metastases, and liver metastases. Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve (AUC) of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis. The portal enhancement ratio (PER) was shown the highest AUC of 0.855 in terms of quantitative features. Our data suggest that the traditional contrast-enhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.
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http://dx.doi.org/10.7555/JBR.34.20200039DOI Listing
August 2020

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Bifunctional polymer brush-grafted coronary stent for anticoagulation and endothelialization.

Mater Sci Eng C Mater Biol Appl 2021 Jan 14;120:111725. Epub 2020 Nov 14.

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China. Electronic address:

At present, cardiovascular stent intervention faces clinical complications such as delayed endothelialization, late thrombosis and restenosis after implantation. In this work, a kind of bifunctional polymer brush-grafted coronary stent with anticoagulant and endothelial functions was developed. First, a block copolymer brush with zwitterionic structure consisting of sulfoethyl methacrylate (SBMA) and glycidyl methacrylate (GMA) was surface-induced grafted onto the surface of bare metal coronary stent by atom transfer radical polymerization. The diethylenetriamine NONOate (DETA NONOate), acted as nitric oxide (NO) donor to promote endothelialization, was then attached to polyglycidyl methacrylate (PGMA) brush by a reactive epoxy group to produce NO. The process of chemical modification and the release behavior of NO were characterized in detail. Moreover, the results of anticoagulant test, cytotoxicity test, endothelial cells (ECs) proliferation test and animal experiment of this bifunctional polymer brush-grafted coronary stent we proposed indicate that the zwitterion modified and NO supplied bifunctional coatings has good anticoagulant property, no cytotoxicity and significant endothelialization effect. This work opens the door to combine biological activity of NO and anticoagulant effect of zwitterions, which has great potential to address post-operative side effects associated with restenosis and late stent thrombosis.
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http://dx.doi.org/10.1016/j.msec.2020.111725DOI Listing
January 2021

Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study.

Langenbecks Arch Surg 2021 May 28;406(3):691-701. Epub 2021 Jan 28.

Pancreas Centre, The First Affiliated Hospital Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, People's Republic of China.

Purpose: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated.

Methods: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery.

Results: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively.

Conclusions: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.
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http://dx.doi.org/10.1007/s00423-021-02080-5DOI Listing
May 2021

A novel rabbit fixator made of a thermoplastic mask for awake imaging experiments.

Sci Rep 2021 Jan 15;11(1):1546. Epub 2021 Jan 15.

PET-CT Center, the First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan Province, China.

This study aimed to develop and validate a novel rabbit fixator made from a thermoplastic mask for awake imaging experiments. When heated in a hot-water bath at 65-70 °C for 2-5 min, the thermoplastic mask became soft and could be molded to fit over the entire body of an anesthetized rabbit (4 ml of 3% pentobarbital sodium solution by intramuscular injection). Twenty rabbits were randomly divided into fixator (n = 10) and anesthesia (n = 10) groups. The animals' vital signs, stress hormones (cortisol and adrenaline), and subjective image quality scores for the computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) scanning were measured and compared. Phantom CT, MRI and PET studies were performed to assess the performance with and without the thermoplastic mask by using image agents at different concentrations or with different radioactivity. The respiration rate (RR), systolic blood pressure (SBP), diastolic blood pressure (DBP), peripheral capillary oxygen saturation (SpO) and body temperature (T) decreased after anesthesia (all P < 0.05) but did not significantly decrease after fixation (all P > 0.05). The heart rate (HR), cortisol and adrenaline did not significantly decrease after either anesthesia or fixation (all P > 0.05). The subjective image quality scores for the CT and MRI images of the head, thorax, liver, kidney, intestines and pelvis and the subjective image quality scores for the PET images did not significantly differ between the two groups (all P > 0.05). For all examined organs except the muscle, F-FDG metabolism was lower after fixation than after anesthesia, and was almost identical of liver between two groups. The phantom study showed that the CT values, standard uptake values and MR T2 signal values did not differ significantly with or without the mask (all P > 0.05). A novel rabbit fixator created using a thermoplastic mask could be used to obtain high-quality images for different imaging modalities in an awake and near-physiological state.
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http://dx.doi.org/10.1038/s41598-021-81358-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810717PMC
January 2021

Evaluation of Twenty-One Cases of Abdominal Tuberculosis: A Single-Center Experience.

Surg Infect (Larchmt) 2021 Apr 17;22(3):299-304. Epub 2020 Jul 17.

Department of General Surgery, The Pancreas Center of Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

Abdominal tuberculosis (TB) remains an issue as it masquerades as many malignant or benign abdominal conditions. To analyze the clinical and laboratory features of abdominal TB retrospectively and discuss its management. The data of patients with a histopathologic diagnosis of abdominal TB seen from January 1, 2008, to February 1, 2019 were collected in The First Affiliated Hospital of Nanjing Medical University. Nodal, visceral, peritoneal, and mixed TB cases were included while excluding other forms of extra-pulmonary TB (EPTB). A total of 21 patients presented having a median age of 49 years (interquartile range 33-57 years) with 12 females and 9 males. Ten presented with abdominal pain, whereas four had abdominal pain and distention. Weight loss was present in five and type 2 diabetes mellitus (DM) in three. Every patient received contrast-enhanced computed tomography (CE-CT) with positive results in all the cases. Seven patients received endoscopic ultrasound-guided fine-needle aspiration cytology examination (EUS-FNAC) and five had results positive for TB. Pre-operative diagnosis of abdominal TB was possible in seven; however, the majority (n = 14) underwent exploratory laparotomy, and all obtained a definitive diagnosis of TB. No deaths occurred. Both CE-CT and EUS-FNAC can aid in the timely diagnosis. Laparotomy is an invasive but efficient tool for the final diagnosis of abdominal TB.
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http://dx.doi.org/10.1089/sur.2020.106DOI Listing
April 2021

Platelet-derived nanomotor coated balloon for atherosclerosis combination therapy.

J Mater Chem B 2020 07;8(26):5765-5775

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, 210023, P. R. China.

Atherosclerosis can lead to thrombosis, blood supply disorders, and even serious consequences such as lumen occlusion or wall rupture and bleeding, so it is urgent to develop an effective comprehensive therapy. Here, a novel kind of drug-coated balloon, where drug-loaded porous nanomotors with autonomous motion ability are used as the coating of the balloon, is reported. The drug-loaded porous nanomotors based on Janus aminated mesoporous silica (JAMS) that was obtained by asymmetric modification of platinum (Pt) nanoparticles are prepared and characterized. The platelet membrane is used to wrap the nanomotors to reduce the leakage of drugs before reaching the plaque. The motion ability of the nanomotor under the irradiation of near-infrared light, the sustained release behavior and effect of the loaded drugs (anti-proliferative drug paclitaxel and the anti-vascular cell adhesion molecule-1 antibody) are investigated in detail. The biomimetic effect and encapsulation effect on drug loading of the platelet membrane, and the elimination of inflammatory macrophages under the photothermal effect produced by Pt are also characterized. The results indicate that the drug-loaded porous nanomotors proposed for drug balloon coating in this work can penetrate into the plaque and enhance the drug retention efficiency, realizing short-term photothermal elimination of inflammatory macrophages and long-term anti-proliferation effect of the drug, providing a possible choice for drug balloon coating with high efficiency in the treatment of atherosclerosis.
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http://dx.doi.org/10.1039/d0tb00789gDOI Listing
July 2020

LPS Induces Active HMGB1 Release From Hepatocytes Into Exosomes Through the Coordinated Activities of TLR4 and Caspase-11/GSDMD Signaling.

Front Immunol 2020 3;11:229. Epub 2020 Apr 3.

Department of Surgery, University of Pittsburgh, Pittsburgh, PA, United States.

High-mobility group box-1 (HMGB1), a ubiquitous nuclear protein, acts as a late mediator of lethality when released extracellularly during sepsis. The major source of circulating HMGB1 in sepsis is hepatocytes. However, the mechanism of HMGB1 release of hepatocytes during sepsis is not very clear. We have previously shown that bacterial endotoxin [lipopolysaccharide (LPS)] sensing pathways, including Toll-like receptor (TLR)4 and caspase-11, regulate hepatocyte HMGB1 release in response to LPS. Here, we report the novel function of caspase-11 and gasdermin D (GsdmD) in LPS-induced active HMGB1 released from hepatocytes. HMGB1 release during endotoxemia was caspase-11/GsdmD dependent via an active way and . Caspase-11/GsdmD was responsible for HMGB1 translocation from nucleus to the cytoplasm via calcium changing-induced phosphorylation of calcium-calmodulin kinase kinase (camkk)β during endotoxemia. Cleaved GsdmD accumulated on the endoplasmic reticulum, suggesting this may lead to calcium leak and intracellular calcium increase. Furthermore, we investigated that exosome was an important pathway for HMGB1 release from hepatocytes; this process was dependent on TLR4, independent of caspase-11 and GsdmD and . These findings provide a novel mechanism that TLR4 signaling results in an increase in caspase-11 expression, as well as increased exosome release, while caspase-11/GsdmD activation/cleavage leads to accumulation of HMGB1 in the cytoplasm through a process associated with the release of calcium from the endoplasmic reticulum and camkkβ activation.
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http://dx.doi.org/10.3389/fimmu.2020.00229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160675PMC
March 2021

Coronary Stents Decorated by Heparin/NONOate Nanoparticles for Anticoagulant and Endothelialized Effects.

Langmuir 2020 03 10;36(11):2901-2910. Epub 2020 Mar 10.

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.

In the treatment of coronary artery disease (CAD), the use of stent implantation often leads to clinical complications such as restenosis, delayed endothelial healing, and thrombosis. Here, we develop a double drug sustained-release coating for the stent surface by grafting heparin/NONOate nanoparticles (Hep/NONOates). The Hep/NONOates and surface modification of the stent were characterized by X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, static water contact angle, and scanning electron microscopy (SEM), and the release behaviors of the anticoagulant, heparin (Hep) and the bioactive molecule, nitric oxide (NO) were studied. Furthermore, the blood compatibility and cytotoxicity of the modified stent were evaluated by whole blood adhesion and platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, plasma recalcification time assay, coagulation time tests, and MTT assay. Finally, the results of a rabbit carotid artery stent implantation experiment showed that the double drug sustained-release coating for the stent can accelerate regeneration of endothelial cells and keep good anticoagulant activity. This study can provide new design ideas based on nanotechnology for improving the safety and effectiveness of drug-eluting stents.
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http://dx.doi.org/10.1021/acs.langmuir.0c00112DOI Listing
March 2020

Utilization of Mobile Application for Better Implementation of Good Clinical Practice in a Biorepository Sample Collection Process: Functions of in Biobanking.

Biopreserv Biobank 2020 Apr 7;18(2):46-52. Epub 2020 Jan 7.

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.

Preanalytical variables of biospecimens play a vital role in biobanking. Currently, there is a lack of a convenient and precise methods to document these variables. Paper documentation and computer-based Lab Information Management System software are the most common solutions, but both have clear disadvantages. An application named was newly developed in our pancreas biobank, with the guidance of good clinical practice principles as well as the incorporation of technical support from professional software companies. With portable electronic devices running this application, all data can be precisely collected in a synchronous manner during sample collection and processing. comprises two major modules-recording and searching-and five submodules in the recording module: blood sample collection, solid tumor tissue sample collection, cystic tumor sample collection, plasma sample separation, and serum sample separation. Compared with other methods, our application was found to be more convenient and accurate in recording preanalytical variables and demonstrated improved capability in facilitating real-time quality control and quality assurance. It was apparent that could improve the integrity of biospecimen and biobank quality management. Thus, it should be considered for further utilization in biobanking.
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http://dx.doi.org/10.1089/bio.2019.0025DOI Listing
April 2020

Prognostic Nomogram for Resected Pancreatic Adenocarcinoma: A TRIPOD-Compliant Retrospective Long-Term Survival Analysis.

World J Surg 2020 04;44(4):1260-1269

Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Background: Prognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors.

Methods: From 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included in this current retrospective long-term survival analysis. Clinicopathological data were extracted from medical records, and all missing values (percentage 0.9-8.3%) were imputed five times with the "PMM" method. Cox proportional hazards models were utilized. A nomogram was formulated based on results from the multivariate regression model so as to predict OS at 1-, 2- and 3-year as well as median OS. Validations, including discrimination and calibration, were carried out with 1000 bootstrap resamples. External validation was conducted in order to verify the accuracy of our nomogram at 1 and 2 years by utilizing the clinicopathological data of 122 PC patients who underwent curative intended surgeries in 2015 in our centre.

Results: Age, abdominal pain, back pain, tumour location, preoperative neutrophil-lymphocyte ratio, preoperative CA19-9, tumour differentiation, microscopic nerve invasion, microscopic vascular invasion, T stage, lymph node ratio, M stage and adjuvant chemotherapy were all assembled into nomogram. The concordance index (C-index) of internal and external validation was 0.702 and 0.688, respectively. The C-index of the TNM staging system was 0.572 (P < 0.001 vs. nomogram).

Conclusion: Our prognostic nomogram based on clinicopathological parameters shows good performance in long-term survival prediction in PC patients following radical surgery and could play a role in further clinical utilization.
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http://dx.doi.org/10.1007/s00268-019-05325-zDOI Listing
April 2020

Multiplet independent resonance modes in multiplexed gratings.

Opt Express 2019 Sep;27(20):28254-28263

Resonance modes in usual optical resonators are orthogonal, but correlated and their resonance properties cannot be independently controlled. Multiplexed gratings, consisting of multiple harmonic grating features, show multiplet resonance modes that can be independently adjusted. This offers flexibility in designing resonance characteristics for various potential applications in nonlinear optics and controlling/enhancement of light-matter interactions, e.g., to resonantly enhance the local densities of photonic modes of both the excitation and emission light in photoluminescence, which cannot be intentionally achieved with conventional resonators. Here we report the design, characteristics and experimental implementation of the multiplexed metal gratings that have doublet or triplet resonance modes. Based on numerical simulations, we investigated dependences of the resonance modes, field distributions and local field enhancements on structure features of the gratings. In implementation, we elaborated the experimental considerations, and demonstrated the consistency in structure features and their resonance characteristics for designed and as-fabricated multiplexed grating resonators.
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http://dx.doi.org/10.1364/OE.27.028254DOI Listing
September 2019

Parenchyma Preserving Surgery for Idiopathic Chronic Calcific Pancreatitis in Children: A Report of Three Cases.

J Pancreat Cancer 2019 3;5(1):51-57. Epub 2019 Oct 3.

Department of General Surgery, The Pancreas Center of Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

Idiopathic chronic calcific pancreatitis is a rare entity. Early surgical intervention and a parenchyma sparing procedure should be advocated to prevent further decay of the pancreas and the occurrence of cancer. Case 1: A 14-year-old boy presented with a 3-year history of right upper abdominal pain that has been aggravated in the last 2 months. Imaging revealed a dilated pancreatic duct of 6 mm with pancreatic duct stones in the head of pancreas. He underwent a Frey's procedure. Unfortunately, he was discharged with grade B pancreatic fistula. Case 2: A 12-year-old boy presented with a 1-year history of dull and recurring epigastric pain. Imaging studies showed multiple stones in a 12 mm dilated pancreatic duct. The patient underwent a modified Puestow procedure. Up to the 42th month follow-up, the patient had no pain complaints. Case 3: A 12-year-old boy with a 1-week history of a dull epigastric pain presented with with multiple stones in a 10 mm duct. He underwent a modified Puestow procedure and was discharged with alleviated pain. "Conservative" surgery allows satisfactory pancreatic duct drainage, reduced rehospitalizations, and longer pain relief than alternative endoscopic procedures.
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http://dx.doi.org/10.1089/pancan.2019.0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776981PMC
October 2019

Mechanical properties and degradation of drug eluted bioresorbable vascular scaffolds prepared by three-dimensional printing technology.

J Biomater Sci Polym Ed 2019 05 7;30(7):547-560. Epub 2019 Apr 7.

a Department of Vascular Surgery , Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School , Nanjing , People's Republic of China.

Bioresorbable vascular scaffolds are expected to replace the traditional metal stent, avoiding the long-term complications of metal stents. However, it is hard for the traditional scaffold manufacturing process to meet the requirements of individualized treatment for vascular lesions, which requires different morphologies. Here, we used a new method of scaffold manufacturing, three-dimensional printing technology, to prepare bioresorbable vascular scaffolds. The fabricated scaffold was loaded with sirolimus mixed with scaffold preparation material for slow drug release. The engineered, drug- loaded, bioresorbable vascular scaffold (BVS) was analyzed and tested in vivo. The scaffolds produced by three-dimensional printing technology exhibited good mechanical properties and in vitro degradation performance. The results also suggested that these scaffolds could maintain effective radial strength after long-term degradation and sustained release of the drug. As a new scaffold preparation method, it may provide a promising idea for developing bioresorbable vascular scaffold technology.
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http://dx.doi.org/10.1080/09205063.2019.1586303DOI Listing
May 2019

Application of 2,4-bis(halomethyl)quinoline: synthesis and biological activities of 2,4-bis(benzofuran-2-yl)- and 2,4-bis(aroxymethyl)quinolines.

Mol Divers 2020 Feb 20;24(1):167-178. Epub 2019 Mar 20.

School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.

In the present investigation, the synthesis of a new type of halomethylquinoline building block, i.e., ethyl 4-(bromomethyl)-2-(chloromethyl)quinoline-3-carboxylate, and its synthetic applications in the reaction with salicylaldehydes or phenols to make a range of structurally novel and intriguing 2,4-bis(benzofuran-2-yl)quinoline- and 2,4-bis(aroxymethyl)quinoline-3-carboxylic acids is described. Our newly synthesized compounds belong to a new class of quinoline derivatives, and their structures were elucidated on the basis of their spectral data and elemental analyses. Screening for in vitro anti-tubercular against Mycobacterium smegmatis and anti-bacterial activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was carried out. Compounds 5e and 5g showed significant anti-tubercular activity comparable with the reference rifampicin and might be used as promising candidates for further investigation.
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http://dx.doi.org/10.1007/s11030-019-09938-3DOI Listing
February 2020

Central pancreatectomy for early-stage pancreatic ductal adenocarcinoma: a single-center case-control study.

Langenbecks Arch Surg 2019 Mar 2;404(2):175-182. Epub 2019 Mar 2.

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

Purpose: Central pancreatectomy (CP) has been applied for treating benign and low-grade malignant tumors in pancreatic neck, but studies regarding CP for pancreatic ductal adenocarcinoma (PDAC) are quite limited. We aimed to investigate the role of central pancreatectomy in the treatment of PDAC in the neck of the pancreas.

Methods: Patients who underwent CP at our hospital between 2009 and 2016 were identified. Patients treated by distal pancreatectomy (DP) were matched according to the tumor size, location, and staging. The surgical and survival outcomes were compared between the CP and DP groups.

Results: Nine patients had CP. Five (56%) had postoperative complications and three (33%) had clinically significant (grade B + C) fistula. No significant difference was found between the CP and DP groups for the rate of overall morbidity, pancreatic fistula, reoperation, and readmission. Tumor size was smaller in the CP group compared to the DP group. The mortality of both groups was zero. The median postoperative survival was similar between the two groups (20.4 months for CP vs 19.4 months for DP, P = 0.842).

Conclusions: CP is safe for patients with small PDAC at the neck of the pancreas. Considering the good preservation of pancreatic endocrine and exocrine functions, CP could be considered as an alternative procedure for single small PDAC in pancreatic neck.
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http://dx.doi.org/10.1007/s00423-019-01766-1DOI Listing
March 2019

Predictors of distant metastasis on exploration in patients with potentially resectable pancreatic cancer.

BMC Gastroenterol 2018 Nov 6;18(1):168. Epub 2018 Nov 6.

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.

Background: Patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC) are frequently found to be unresectable on exploration due to small distant metastasis. This study was to investigate predictors of small distant metastasis in patients with potentially resectable PDAC.

Methods: Patients who underwent surgical exploration for potentially resectable PDAC from 2013 to 2014 were reviewed retrospectively and divided into two groups according to whether distant metastases were encountered on exploration. Then, univariate and multivariate logistic regression analyses were used to identify predictors of distant metastasis. A scoring system to predict distant metastasis of PDAC on exploration was constructed based on the regression coefficient of a multivariate logistic regression model.

Results: A total of 235 patients were included in this study. Mean age of the study population was 61.7 ± 10.4 years old. Upon exploration, distant metastases were found intraoperatively in 62 (26.4%) patients, while the remaining 173 were free of distant metastases. Multivariate logistic regression analysis identified that age ≤ 62 years old (p < 0.001), male sex (p = 0.011), tumor size ≥4.0 cm (p < 0.001), alanine aminotransferase level (ALT) < 125 U/L (p < 0.001), and carbohydrate antigen (CA19-9) level ≥ 385 U/mL (p < 0.001) were independent risk factors for occult distant metastasis of PDAC. A preoperative scoring system (0-8 points) for distant metastasis on exploration was constructed using these five factors. The receiver operating characteristic curves showed that the area under the curve of this score was 0.85. A score of 6 points was suggested to be the optimal cut-off value, and the sensitivity and specificity were 85% and 69%, respectively.

Conclusions: Distant metastasis is still frequently encountered on exploration for patients with potentially resectable PDAC. Younger age, male sex, larger tumor size, low ALT level and high CA19-9 level are independent predictors of unexpected distant metastasis on exploration.
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http://dx.doi.org/10.1186/s12876-018-0891-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220565PMC
November 2018

Afferent Loop Decompression Technique is Associated with a Reduction in Pancreatic Fistula Following Pancreaticoduodenectomy.

World J Surg 2018 11;42(11):3726-3735

Department of General Surgery, Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

Objectives: Postoperative pancreatic fistula (POPF) is a major complication and main cause of mortality after pancreaticoduodenectomy (PD). Afferent loop decompression technique (ALDT) has theoretical feasibility to reduce the rate of POPF. The aim of this study is to determine whether ALDT is a protective factor for POPF.

Methods: A total of 492 consecutive patients who underwent PD between January 2012 and December 2014 were identified from a prospective database. All data were extracted and events were judged based on medical records. Propensity score matching was conducted to balance several variables. Univariate and multivariate analyses were performed, respectively, to investigate the independent risk factors for pancreatic fistula. ALDT required a nasogastric tube with multiple side holes to be placed deep into the afferent jejunal limb. The rationale for this technique was to prevent pancreatic fistula by decreasing intraluminal pressure in the afferent jejunal loop by placement of the nasogastric tube and the application of continuous low-pressure suction after surgery.

Results: The total rate of POPF for the entire cohort was 30.7%, and ISGPS grade-A/B/C POPF rates were 18.1, 10.6 and 2.0%, respectively. In-hospital mortality was 1.6%. Among the 331 patients who received ALDT, 89 developed pancreatic leakage (26.9 vs. 38.5% for non-ALDT; P = 0.009) and eight developed biliary leakage (2.4 vs. 6.2% for non-ALDT; P = 0.035). Apart from ALDT, decreased preoperative ALT, soft pancreas, long operative time and tumour presence in the lower common bile duct (as opposed to the pancreas) were identified as other independent risk factors for POPF following multivariate logistic regression analysis.

Conclusions: ALDT may reduce the incidence of POPF after PD.
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http://dx.doi.org/10.1007/s00268-018-4679-6DOI Listing
November 2018

PRSS1 and SPINK1 Mutations in Alcoholic and Idiopathic Chronic Pancreatitis.

J Nanosci Nanotechnol 2017 Apr;17(4):2358-362

Several recent studies have reported associations between gene mutations and chronic pancreatitis (CP); however, little is known about their association with risk of CP in the Chinese Han population. The aim of this study was to describe mutations in the cationic trypsinogen (PRSS1) and serine protease inhibitor Kazal type 1 (SPINK1) genes in patients with alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis (ICP) and to investigate their influence on the clinical course of the disease. One hundred patients (24 with ACP, 76 with ICP) and 100 healthy volunteers (control group) were enrolled in the study. PRSS1 (R122H) mutations were detected in one (1.3%) patient with ICP and SPINK1 (N34S) mutations were present in one (4.1%) patient with ACP. PRSS1 and SPINK1 mutations were not detected in the control populations. There were no statistically significant differences between the CP patients and the control group. Those preliminary data suggest low prevalence of SPINK1 and PRSS1 mutations in the Chinese population, generally, as well as in CP patients, indicating that these mutations do not contribute to the development of CP.
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http://dx.doi.org/10.1166/jnn.2017.12626DOI Listing
April 2017

Diagnosis and treatment of solid-pseudopapillary tumors of the pancreas: A single institution experience with 97 cases.

Pancreatology 2018 Jun 24;18(4):415-419. Epub 2017 Dec 24.

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. Electronic address:

Background/objectives: We evaluated the diagnoses and surgical management of solid pseudopapillary tumors of the pancreas (SPTP) in a single center setting.

Methods: Demographic details, clinical presentations, imaging features, surgical strategies, and pathological findings of 97 consecutive patients who underwent surgery for pathologically confirmed SPTP between 2008 and 2016 were analyzed retrospectively.

Results: A total of 97 patients with SPTP accounted for 2.15% of total pancreatic surgeries (N = 4508). The mean age at diagnosis was 31.6 ± 13.92 years (range: 7-83 years), and males:females were 85:12. Chief complaints were abdominal pain or discomfort (n = 50). The mean transverse tumor diameter was 53.2 ± 2.76 mm (range: 14-170 mm). Tumors were localized to the pancreatic head (38.1%; 37/97), neck (12.4%; 12/97), body and tail (49.5%; 48/97). There were no significant differences in age of onset, presenting symptoms, and sites between males and females. A significant difference was found in the maximum diameter of SPTP across different age groups. Partial pancreatectomy was performed for patient with tumor ≥ 5 cm, and enucleation was performed when tumor was smaller than 5 cm. Pancreatic fistula was the main complication. Immunohistochemical markers for endocrine, exocrine and epithelial factors were used for a final diagnosis. During a median follow-up of 54 months (range: 7-121 months), 84 patients were alive without evidence of recurrence, and 13 patients were lost to follow-up.

Conclusion: SPTP surgical resection is a safe procedure with low morbidity and mortality, which is also effective even in the presence of invasiveness and metastases. Accurate initial diagnoses and follow up are essential.
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http://dx.doi.org/10.1016/j.pan.2017.12.012DOI Listing
June 2018

Anomalous resonant reflection in a Fabry-Perot cavity filled with weakly scattering medium.

Opt Lett 2018 Mar;43(5):1159-1162

In this work, we fabricated a metallic Fabry-Perot cavity, filled with a weakly scattering medium of unsintered solgel silica, on a glass substrate. We found anomalous asymmetric resonance reflection spectra of this structure, besides the effects of scattering loss in cavity. The asymmetric reflection is shown to be dependent on the media on both sides of the cavity. It is thought that, as the weakly scattering medium locates between highly reflecting boundaries and the cavity length is far less than the mean free path of light in the medium, light scattering in the medium is enhanced at the resonance conditions and the scattering centers act as elementary sources emitting the scattered incoherent light to the outside of the cavity from both its ends. The asymmetric reflection then results from lossy total internal reflection of the scattered light at one of the boundaries, eventually leaking to the outside of the cavity with the higher index and contributing to the measured backside reflectance.
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http://dx.doi.org/10.1364/OL.43.001159DOI Listing
March 2018

Black pleural effusion due to pancreatic pseudocyst: A case report.

Medicine (Baltimore) 2017 Dec;96(50):e9043

Pancreas Center, First Affiliated Hospital Pancreas Institute, Nanjing Medical University, Nanjing, P.R. China.

Rationale: Black pleural effusion (BPE) is an extremely uncommon type of pleural fluid, which can be due to infection, primary or metastatic malignancy, and hemorrhage. As reported in previous studies, BPE is also observed in some patients with pancreatic pseudocyst.

Patient Concerns: We herein reported a case of a 14-year-old female patient who was admitted to our center with a history of cough for 1 and a half months and right chest pain for 1 month. Before this, she was consecutively hospitalized in 3 different hospitals due to the same symptoms. However, the previous treatments were ineffective due to the lack of a definitive diagnosis. Laboratory examination of the pleural effusion showed BPE with a high amylase concentration. Chest x-ray and computed tomography (CT) showed massive pleural effusion, more prominent in the right chest. CT and MRCP of the abdomen showed a cystic lesion located in the tail of the pancreas, which entered the chest cavity via an esophageal hiatal hernia. DIAGNOSES:: pancreatic pseudocyst.

Interventions: After confirming that the tumor was a pancreatic pseudocyst by intraoperative biopsy, internal drainage to the jejunum was performed.

Outcomes: The postoperative recovery was rapid and without complications, and the final discharge diagnosis was idiopathic pancreatic pseudocyst (without history of pancreatitis or pancreatic injuries) with BPE of the right chest.

Lessons: This case demonstrates that massive BPE could present as a rare complication of pancreatic pseudocyst, and surgery is a potential treatment for such patients.
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http://dx.doi.org/10.1097/MD.0000000000009043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815711PMC
December 2017

Application of intraoperative transluminal core-biopsy for diagnosis of pancreatic head mass: A single center 15-year experience.

Pancreatology 2018 Jan 4;18(1):68-72. Epub 2017 Sep 4.

Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address:

Background: Pathology is the gold standard for diagnosis of pancreatic cancer. Preoperative endoscopic ultrasound-guided biopsy is an expensive procedure that is not routine in developing countries, hence a cheap, reliable alternative is required.

Aim: To evaluate the effectiveness and safety of a new technique of intraoperative biopsy from pancreatic head mass.

Methods: Patients undergoing intraoperative transluminal core-biopsy (TLCB) for pancreatic head mass from January 2000 to June 2015 were included in this study. Following Kocher's maneuver, a biopsy was taken from the mass through the duodenum transluminally, using a commercial 16G automatic core-biopsy needle. Multiple tissue specimens were obtained for intraoperative frozen section examination. Depending on the pathological results, a decision was taken to either perform pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, bypass surgery, or to just terminate the operation. The malignancy status of the lesion was confirmed by postoperative pathological examination and/or long-term follow-up of the patients.

Results: A total of 525 patients were included. Intraoperative pathological reports revealed 436 malignant cases and 89 cases without evidence of malignancy. The sensitivity, specificity, false positive rate, and false negative rate were 97.7%, 100%, 0%, and 2.3%, respectively. Complications occurred in 2 patients.

Conclusion: TLCB is a quick, safe, effective, and accurate method for intraoperative diagnosis method in patients with pancreatic head mass; it can provide reliable evidence for surgical decision-making.
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http://dx.doi.org/10.1016/j.pan.2017.09.001DOI Listing
January 2018

MicroRNA-217 inhibits cell proliferation, invasion and migration by targeting Tpd52l2 in human pancreatic adenocarcinoma.

Oncol Rep 2017 Dec 16;38(6):3567-3573. Epub 2017 Oct 16.

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

MicroRNAs (miRNAs) play important roles in the regulation of various tumor biological processes including proliferation and apoptosis. miR-217 has been implicated in many types of cancer, whereas its expression and potential biological function in human pancreatic adenocarcinoma (HPAC) remain unclear. We aimed to investigate the clinical significance of miR-217 in patients with pancreatic carcinoma and its role and underlying molecular mechanism in HPAC. We collected 15 pairs of pancreatic cancer and normal pancreas tissues to evaluate the expression of miR-217 and tumor protein D52-like 2 (Tpd52l2). Then, we transfected AsPC-1 cells with miR-217 mimics or Tpd52l2 siRNA to detect the effect on cell proliferation, apoptosis, invasion, migration and the cell cycle. In addition, miR-217 mimics and Tpd52l2 expression plasmids were co-transfected into AsPC-1 cells to further investigate the mechanism of miR-217 and Tpd52l2 in HPAC tumorigenesis. Finally, exploration of related signaling pathways was carried out. Herein, we found that the expression of miR-217 was significantly downregulated in HPAC tissues as compared with that observed in adjacent normal tissues. Further functional assays showed that restoration of the expression of miR-217 inhibited cell proliferation, invasion and migration, induced apoptosis, and caused cell cycle arrest of HPAC cells. Notably, Tpd52l2 was identified as a functional target of miR-217 in HPAC. Furthermore, an inverse correlation between miR-217 and Tpd52l2 expression was observed in the HPAC tissues. Downregulation of Tpd52l2 had an effect similar to that following overexpression of miR-217, and upregulation of Tpd52l2 reversed the effects of the overexpression of miR-217. Finally, we found that overexpression of miR-217 or knockdown of Tpd52l2 suppressed the PIK3CA/AKT signaling pathways. In addition, this may explain the effect of miR-217/Tpd52l2 on HPAC development. Taken together, these results suggest a critical role of miR-217 in suppressing proliferation, migration and invasion of HPAC cells by targeting Tpd52l2. Targeting the miR-217/Tpd52l2 axis may be a new therapeutic application with which to treat patients with HPAC in the future.
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http://dx.doi.org/10.3892/or.2017.6036DOI Listing
December 2017

A simple and facile synthesis of tricyclic-fused pyrimido[4,5-b]indol-2-amines.

Mol Divers 2017 Nov 19;21(4):831-840. Epub 2017 Jun 19.

Institute of Superfine Chemicals, Bohai University, Keji Street, Jinzhou, 121000, People's Republic of China.

In the present investigation, a simple and facile synthetic strategy for the construction of a series of structurally interesting tricyclic-fused N-alkyl-9H-pyrimido[4,5-b]indol-2-amines has been successfully achieved. Our synthesis, based on the annulation reaction between readily available 2-chloroindole-3-carbaldehydes or 3-acetyl-2-chloroindoles and guanidine nitrate using KOH as the base in refluxing EtOH medium, has the attractive features such as mild and economical reaction conditions and easy handing with lesser impact on the environment.
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http://dx.doi.org/10.1007/s11030-017-9757-4DOI Listing
November 2017

The clinical value, regulatory mechanisms, and gene network of the cancer-testis gene STK31 in pancreatic cancer.

Oncotarget 2017 May;8(21):35154-35164

Pancreatic Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.

We aimed to identify STK31 as a cancer-testis (CT) gene and to explore its potential clinical value, regulatory mechanisms, and gene network in pancreatic cancer (PC). Gene expression data were generated from normal organ samples and pancreatic cancer samples from three public databases. STK31 expression patterns in normal and PC tissues were identified, and we explored its regulatory mechanisms. Gene ontology (GO) and pathway analyses of STK31-related genes were performed and an STK31 protein-protein interaction (PPI) network was constructed. STK31 was confirmed as a CT gene in PC and its expression was significantly higher in patients with new neoplasm compared with patients without new neoplasm (P = 0.046) and in more advanced pathologic stages than in earlier stages (P = 0.002); methylation level correlated negatively with STK31 expression. In total, 757 STK31-related genes were identified, and were significantly enriched in terms of polymorphisms and alternative splicings. The PPI network predicted that STK31 was physically associated with the PIWI (originally P-element Induced WImpy testis in Drosophila) and Tudor families.
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http://dx.doi.org/10.18632/oncotarget.16814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471042PMC
May 2017

Vasohibin 2 reduces chemosensitivity to gemcitabine in pancreatic cancer cells via Jun proto-oncogene dependent transactivation of ribonucleotide reductase regulatory subunit M2.

Mol Cancer 2017 03 21;16(1):66. Epub 2017 Mar 21.

Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People's Republic of China.

Background: Vasohibin 2 (VASH2) has previously been identified as an agiogenenic factor and a cancer related protein. Here we investigated the association of VASH2 expression and chemoresistance in pancreatic cancer.

Methods: Immunohistochemical staining for VASH2 was performed on 102 human pancreatic cancer samples. Pancreatic cancer cell line models exhibiting overexpression or knockdown of VASH2 were generated. Gene expression analyses were carried out to determine genes differentially regulated by VASH2. Putative transcription factors that are downstream mediators of gene expression regulated by VASH2 were queried bioinformatically. Dual-luciferase reporter assays and ChIP assays were performed to confirm transactivation of target genes following VASH2 overexpression or knockdown.

Results: VASH2 protein expression was higher in human pancreatic cancer than in paired adjacent tissues and elevated VASH2 levels were associated with gemcitabine chemoresistance. In cell line models of pancreatic cancer, VASH2 expression induced gemcitabine chemoresistance in vitro and in vivo. It was discovered that expression of ribonucleotide reductase regulatory subunit M2 (RRM2) is regulated by VASH2; immunohistochemical analysis demonstrated a positive association of VASH2 expression and RRM2 expression in human pancreatic cancer tissues. Bioinformatics analyses revealed that induction of the Jun proto-oncogene (JUN) by VASH2 is responsible for upregulation of RRM2 expression; this JUN-dependent regulation of RRM2 by VASH2 was confirmed by chromatin immunoprecipitation and dual luciferase reporter assays, which demonstrated that JUN directly binds with the RRM2 promoter to activate transcription.

Conclusions: These data suggest that VASH2 reduces the chemosensitivity to gemcitabine in pancreatic cancer cells via JUN-dependent transactivation of RRM2.
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http://dx.doi.org/10.1186/s12943-017-0619-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360034PMC
March 2017