Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

【Objective】 To explore the role of visfatin-nicotinamide phosphoribosyl transferase （Nampt） axis in the progression of epithelial ovarian cancer （EOC） and its effect on the patients’ prognosis. 【Methods】 Immunohistochemical analysis was used to detect the expression of Nampt protein in tissues from epithelial ovarian cancer and normal ovary； ELISA was used to determine the level of visfatin in serum. Then the two were further analyzed to estimate their effects on clinicopathological characteristics and the EOC patients’ overall survival. 【Results】 The mean level of serum visfatin in these EOC patients was significantly elevated compared with that of the patients with benign ovarian tumors and normal population. ROC curve analysis showed that the area under curve （AUC） of serum visfatin for diagnosis of EOC was 0.744， with a cut-off value of 5.95 ng/mL. Serum visfatin of the EOC patients was related to T， N and FIGO stage （P<0.05）， and was positively correlated with CA125 （rs=0.389， P=0.001）. The rate of Nampt positive expression in tissues from EOC was significantly increased and correlated with FIGO stage and serum visfatin （P<0.05）. Nampt protein expression in EOC was positively correlated with serum visfatin level （rs=0.55， P<0.001）. The 1-year， 3-year and 5-year survival rate of these patients with EOC was 98.6%， 74.3% and 34.3%， respectively. Survival analysis demonstrated that the overall survival of these patients was related to T， N， FIGO stage， serum visfatin and Nampt expression in EOC， and both FIGO stage and Nampt expression were independent prognostic factors （P<0.05）. 【Conclusion】 The overall survival of these EOC patients was related to T， N， FIGO stage， serum visfatin and Nampt expression， and FIGO stage and Nampt expression are independent factors predicting the outcome. This highlights that visfatin-Nampt axis promotes the progression of epithelial ovarian cancer and affects the prognosis of EOC patients.

【Objective】 To explore the key genes and potential therapeutic drugs for ER-negative breast cancer by bioinformatics. 【Methods】 The gene expression profile of breast cancer (GSE22219) was downloaded from the Gene Expression Omnibus (GEO). Principal components analysis (PCA) of GSE22219, and analyses of differentially expressed genes (DEGs) between the ER-negative and ER-positive subjects and Gene Ontology (GO) analysis were performed by R software. We analyzed The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Protein-Protein Interaction (PPI) network using STRING. The hub genes were identified using Cytoscape and analyzed using online programs. Drugbank analysis was used to find small molecular compounds as potential therapeutic agents to target the DEGs. 【Results】 We detect 69 DEGs and 8 hub genes between the ER-negative and ER-positive subjects. We found the most significant KEGG pathway of DEGs was aldosterone-regulated sodium reabsorption. The Gene Ontology (GO) analysis indicated that the most significantly enriched in prostate gland morphogenesis. Totally 21 small molecular compounds were identified as potential therapeutic agents for ER-negative breast cancer. 【Conclusion】 The bioinformatical analysis combined with drug database can help us find potential therapeutic agents to treat diseases. This method is a new paradigm which can guide future research on drugs.

Objective:To comparatively evaluate the scan time and the accuracy of maxillary full-arch scans using four intraoral scanners (IOS) on conditions of the intraoral head-simulator and the hand-held model, and to evaluate the influence of different scanning conditions on digital scan.Methods:A upper dental arch model with melamine-formaldehyde resin teeth and silica gel gingiva that could be fixed on a head simulator was scanned with an optical scanner (ATOS Core) in order to obtain the standard tessellation language dataset as reference. Intraoral scans were performed on the model fixed on the head simulator by three researchers with four IOS [A: TRIOS 3; B: CS 3600; C: CEREC Omnicam; D: iTero]. For each scanner and each researcher, six scans were performed, to obtain the datasets as the head simulator group. And another six scans with each of the four intraoral scanners were performed by each researcher on the hand-held model to obtain the STL datasets as the hand-held group. The scan time were recorded for each scan. In the Geomagic Wrap software, the digital models were trimmed with only the teeth information retained and supreimposed by best fit alignment function and compared to obtain the root mean square (RMS) values of the discrepancies by three-dimensional compare function. The test datasets of each group were compared with the reference dataset for trueness. The six test scanning datasets with the same scanner of the same researcher were cross compared for precision. Mann Whitney U test was used to statistically analyze the difference values of the scan time, trueness and precision of the same intraoral scanner between head simulator group and hand-held group. Results:Compared to the hand-held group, the scan time of A [142(82) s] and D [119(52) s], which two IOS both with handle, were longer in head simulator group [A: 98(28) s; D: 85(22) s] ( P<0.01). However there were no significant differences between the two groups for scan time of IOS B and C ( P>0.05). For full-arch scan accuracy (trueness and precision), there were no significant differences between the two groups of IOS A and B ( P>0.05), while the trueness of C ( P<0.05) and the precision of D ( P<0.01) were better in head simulator group [C: 112(38) μm; D: 43(13) μm] compared to hand-held group [C: 135(47) μm; D: 53(18) μm]. However, there were no significant differences for the precision of C ( P>0.05) and the trueness of D ( P>0.05). Conclusions:The scan time and the accuracy of full-arch digital scans with different IOS may be effected by the scan conditions. For in vitro study of intraoral scanning, head-simulator can simulate the intraoral environment of the real patient to some extent. Meanwhile, the position of the dentist and the patient, and also the limited intraoral space during intraoral scanning are also simulated.

Objective: To investigate the contamination status of Salmonella, Vibrio parahaemolyticus and Staphylococcus aureus and bacterial resistance in retail meat products in Taiyuan, Shanxi Province. Methods: In the epidemic season of diarrhea in 2017, poultry and meat product specimens were randomly collected from the farmer′s markets and supermarkets of 10 districts and counties of Taiyuan. Salmonella, Vibrio parahaemolyticus and Staphylococcus aureus were isolated form these specimens. Serotypes of Salmonella strains were analyzed. ELSIA was used to detect Staphylococcus aureus enterotoxin (A-E). Vibrio parahaemolyticus isolates were tested for the virulence genes encoding direct hemolysin (tdh) and indirect hemolysin (trh). Antibiotic resistance of the three food-borne pathogens were analyzed using microdilution methods. Results: A total of 38 food-borne pathogens were isolated from 123 poultry and livestock meat product specimens with a positive rate of 30.9%, of which mainly were Salmonella (26 strains, 21.1%), followed by Vibrio parahaemolyticus (8 strains, 6.5%) and Staphylococcus aureus (4 strains, 3.3%). The 26 strains of Salmonella belonged to 10 serotypes. The Salmonella strains isolated from pork specimens had diverse serotypes. Salmonella serovar Derby, Salmonella serovar Gold-coast and Salmonella serovar Liverpool were isolated from raw and cooked pork food for the first time in Taiyuan. All Salmonella strains isolated form chicken products were Salmonella enteritis. The enterotoxin types of the four Staphylococcus aureus strains were three E-type and one complex type (A/E). All Vibrio parahaemolyticus isolates were negative for tdh or trh gene. Ampicillin, chloramphenicol, streptomycin, sulphonamides and tetracyclines (ACSSuT) resistance was prevalent in multi-drug resistant (MDR) Salmonella strains, but there was high sensitivity to fluoroquinolones and cephalosporins. MDR Staphylococcus aureus accounted for 75%. No third-generation cephalosporin- or fluoroquinolone-resistant or MDR Vibrio parahaemolyticus strains were isolated. Conclusions There were food-borne multi-pathogenic bacteria contamination in retail raw and cooked meat products in Taiyuan. Salmonella strains had diverse serotypes and high MDR rate. It was suggested that the regulatory authorities should strengthen the management of antibiotic use in aquaculture and specialized laboratory-based monitoring of meat supply chain.

Objective: To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods: From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay. Results: The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues (P<0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues (P<0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p (r=-0.613, P=0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P<0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3′-UTR reporter assay confirmed that miRNA-96-5p binds to the 3′UTR of FoxQ1. Conclusion miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.

Objective To investigate the role of microRNA?96?5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA?96?5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para?cancerous tissues were quantified by quantitative real?time PCR (qRT?PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA?96?5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA?96?5p in gastric cancer tissue and adjacent normal tissue were detected by qRT?PCR. miRNA?96?5p mimics was transfected to BGC?823 gastric cancer cells. The effects of miRNA?96?5p on cell proliferation and invasion were detected by cell counting kit?8 (CCK?8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E?cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA?96?5p expressed in BGC?823 cells was detected by dual?luciferase reporter assay. Results The median expression of miRNA?96?5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para?cancerous tissues (P＜0.05).The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para?cancerous tissues ( P＜0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA?96?5p (r＝－0.613, P＝0.006). The expression of miRNA?96?5p in gastric cancer cell BGC?823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84± 0.15, P＜0.05). The results of CCK?8 assay and Transwell assay showed that overexpression of miRNA?96?5p significantly reduced the proliferation and invasion abilities of gastric cancer cells ( P＜ 0.05 ). Overexpression of miRNA?96?5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E?cadherin and downregulated the expression of vimentin. The result of dual?luciferase?3′?UTR reporter assay confirmed that miRNA?96?5p binds to the 3′UTR of FoxQ1. Conclusion miRNA?96?5p may suppress the proliferation, migration and epithelial?mesenchymal transition (EMT) of gastric cancer cell by down?regulation of FoxQ1.

Objective To investigate the role of microRNA?96?5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism. Methods From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA?96?5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para?cancerous tissues were quantified by quantitative real?time PCR (qRT?PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA?96?5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA?96?5p in gastric cancer tissue and adjacent normal tissue were detected by qRT?PCR. miRNA?96?5p mimics was transfected to BGC?823 gastric cancer cells. The effects of miRNA?96?5p on cell proliferation and invasion were detected by cell counting kit?8 (CCK?8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E?cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA?96?5p expressed in BGC?823 cells was detected by dual?luciferase reporter assay. Results The median expression of miRNA?96?5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para?cancerous tissues (P＜0.05).The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para?cancerous tissues ( P＜0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA?96?5p (r＝－0.613, P＝0.006). The expression of miRNA?96?5p in gastric cancer cell BGC?823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84± 0.15, P＜0.05). The results of CCK?8 assay and Transwell assay showed that overexpression of miRNA?96?5p significantly reduced the proliferation and invasion abilities of gastric cancer cells ( P＜ 0.05 ). Overexpression of miRNA?96?5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E?cadherin and downregulated the expression of vimentin. The result of dual?luciferase?3′?UTR reporter assay confirmed that miRNA?96?5p binds to the 3′UTR of FoxQ1. Conclusion miRNA?96?5p may suppress the proliferation, migration and epithelial?mesenchymal transition (EMT) of gastric cancer cell by down?regulation of FoxQ1.

Objective To assess the value of serum carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels in the diagnosis of gastric cancer in elderly patients.Methods This prospective study included 104 elderly patients with gastric cancer at our hospital from March 2015 to December 2016 to serve as an experimental group.Moreover,104 elderly patients with benign gastric lesions were enrolled to serve as a control group.Serum CEA and CA19-9 levels were compared between the two groups.The diagnostic specificity,sensitivity,and validity for gastric cancer were calculated by using CEA or CA19-9 alone or the two in combination.Results Serum CEA and CA19-9 levels in the experimental group were significantly higher than in the control group(t =3.001 and 5.110,P =0.039 and 0.016,respectively);The specificity,sensitivity,and validity of CEA and CA19-9 in combination were significantly higher than when each of the measures was used alone(x2 =2.101 and 2.109,P =0.031 and 0.019,respectively).Serum CEA levels showed good predictive power for both lymph node metastasis of gastric cancer(Z =5.109,P =0.002) and liver metastasis of gastric cancer(Z =3.910,P =0.026);Serum CA19-9 levels could predict lymph node metastasis of gastric cancer (Z =4.189,P =0.003) Conclusions Serum CEA and CA19-9 in combination have high sensitivity and validity for gastric cancer detection;Elevated CEA can predict gastric cancer metastasis and elevated CA19-9 may predict lymph node metastasis.