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Yanrui Liang,1,* Weihong Guo,1,* Chuangji Li,1,* Guodong Shen,1,* Haoxian Tan,2 Peiwen Sun,2 Zhian Chen,1 Huilin Huang,1 Zhenhao Li,1 Zhenyuan Li,1 Yingxin Ren,1 Guoxin Li,1 Yanfeng Hu1 1Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoxin Li; Yanfeng Hu, Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Ave, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1681 ; +86-20-6164-1682, Fax +86-20-6164-1681, Email yfenghu@qq.com; gzliguoxin@163.comPurpose: Lymphadenectomy with lymph node (LN) mapping is essential for surgical removal of solid tumors. Existing agents do not provide accurate multimodal mapping and antitumor therapy for metastatic LNs; therefore, we fabricated a polydopamine (PDA) nanoparticle (NP)-based tumor-targeted LN mapping agent capable of multimodal mapping and guided photothermal therapy (PTT) for metastatic LNs.Materials and Methods: PDA NPs modified with polyethylene glycol (PEG) were obtained by polymerization under alkaline conditions. The PEG-PDA NPs were loaded with the circular tripeptide Arg-Gly-Asp (cRGD) to achieve tumor-targeting capacity and with the fluorescent dye IR820 and magnetic resonance imaging (MRI) contrast Gd(NH2)2 for in situ detection. The resulting cRGD-PEG-PDA@IR820/Gd(NH2)2 (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αvβ 3 integrin-mediated endocytosis.Results: This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice.Conclusion: In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.Keywords: multimodal imaging, lymph node mapping, metastatic lymph node, photothermal therapy

Background The benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy. Methods This was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined. Results There were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1−/3−/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1−/3−/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357–0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322–0.811, P = 0.004) in stage III patients. Conclusions This study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

Background Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp. Results In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity. Conclusions In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy. Graphic Abstract

Additional file 1. Additional figures S1–S20.

CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells’ apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells’ mitochondrial fusion, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd), which exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined PDT and mild PTT (43-45 °C) under mild NIR power density (0.8W/cm2). Surprisingly, it was found that PTT might not be the key factor of cell apoptosis, as ROS induced by PDT seems playing a more essential role. The NIR-induced ROS could attack mitochondrial membrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial fusion dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/ IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. Taken together, HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial fusion on GC.

Background: CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells’ apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells’ mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd).Results: HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/ IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. Conclusion: HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

Additional file 1. Additional Figures S1–S21.

Among various methods, the use of targeting nucleic acid therapy is a promising method for inhibiting gastric cancer (GC) cells' rapid growth and metastasis abilities. In this study, vitamin B12-labeled poly (d,l-lactide-co-glycolide) and polyethylene glycol nanoparticles (PLGA-PEG-VB12 NPs) were developed for microRNAs-532-3p mimics incorporating as targeting gene delivery systems (miR-532-3p@PLGA-PEG-VB12 NPs) to fight against transcobalamin II (CD320)-overexpressed GC cells' progression. The PLGA-PEG-VB12 NPs with appropriate particle sizes and good bio-compatibility could be selectively delivered into CD320-overexpressed GC cells, and significantly decrease the expression of apoptosis repressor with caspase recruitment domain (ARC). Following that, more pro-apoptotic protein (Bax) flowed from cytoplasm into mitochondria to form Bax oligomerization, thus induced mitochondrial damage, including mitochondrial membrane potentials (MMPs) loss and excessive production of mitochondrial reactive oxygen species (mitoROS). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by induced more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-depended cell apoptosis pathway. Therefore, our designed miR-532-3p@PLGA-PEG-VB12 NPs showed enhanced GC targeting ability, and could induce apoptosis through activating ARC/Bax/mitochondria-mediated apoptosis signaling pathway, finally remarkably suppressed proliferation of GC cells both in vitro and in vivo, which presented a promising treatment for GC.

Staphylococcus aureus (S. Aureus) is a common food-borne pathogenic microorganism. Biofilm formation remains the major obstruction for bacterial elimination. The study aims at providing a basis for determining S. aureus biofilm formation. 257 clinical samples of S. aureus isolates were identified by routine analysis and multiplex PCR detection and found to contain 227 MRSA, 16 MSSA, 11 MRCNS, and 3 MSCNS strains. Two assays for quantification of S. aureus biofilm formation, the crystal violet (CV) assay and the XTT (tetrazolium salt reduction) assay, were optimized, evaluated, and further compared. In CV assay, most isolates formed weak biofilm 74.3 %), while the rest formed moderate biofilm (23.3 %) or strong biofilm (2.3 %). However, most isolates in XTT assay showed weak metabolic activity (77.0 %), while the rest showed moderate metabolic activity (17.9 %) or high metabolic activity (5.1 %). In this study, we found a distinct strain-to-strain dissimilarity in terms of both biomass formation and metabolic activity, and it was concluded from this study that two assays were mutual complementation rather than being comparison.

Gram-positive microorganisms comprise one of the leading pathogenic microorgan- isms in public health, including several 'Superbugs' such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, which have posed a dilemma for the treatment of infectious diseases caused by Gram-positive bacteria and will consequently result in an increasing number of clinical failures. Integrons have been established as a significant resistance determinant and shown to contribute to the multiresistance of microorganisms; however, its role in antimicrobial resistance in Gram-positive microorganisms still remains unclear and somehow neglected. In the last decade, integron surveillance has been conducted for various clinical microorganisms in Guangzhou, China, and based on this study this review aims at summarizing the occurrence and prevalance of integrons and their role in the antimicrobial resistance of Gram-positive microorganisms. 2015 Wolters Kluwer Health, Inc. All rights reserved. Reviews in Medical Microbiology 2015, 26:26-31

Staphylococcus is a common gram-positive pathogen, which has been considered to be a leading concern to public health and food safety due to the multi-drag resistance and virulence. As is known, most Staphylococcus tend to form biofilm both during various food processing procedures and in environment, and the bacteria in biofilms show a number of specific advantages over planktonic bacteria due to strong resistance ability. As a consequence, inhibition and removal of Staphylococcus biofilm is difficult for food safety during processing. The present review aims to discuss and demonstrate the formation and development of Staphylococcus biofilm based on food safety account under the background of both phenotype and genetic regulation, providing scientific reference for control strategy. Practical application As a common foodborne pathogen, Staphylococcus aureus in food industry is a potential harm to the health of both customer and stuff. Biofilm plays a significant role in bacterial survival, tolerant to environmental stresses. Thus, a comprehensive understanding of biofilm is of essential and urgent need. This review of biofilm of Staphylococcus aureus illustrated the biofilm in food industry and its formation, influential factor, quantification, genetic regulation mechanism, and control strategies, which provided a background of Staphylococcus aureus biofilm prevention in food industry.