Performance evaluation of a novel 14C-urea breath test (solid scintillation) for the diagnosis of helicobacter pylori infection.

14C-urea breath tests (UBTs) can be used to diagnose helicobacter pylori (H. pylori) infection. This study aimed to evaluate the accuracy of a solid scintillation 14C-UBT in diagnosing H pylori infection. This open-label, prospective multicenter study enrolled patients who underwent H pylori screening from January 7, 2020, to October 28, 2020, in 3 centers in China. All participants underwent solid scintillation UBT first and then gastroscopy. The rapid urease test and histological examination results were the gold standards (H pylori-positive was defined as the 2 tests being positive; H pylori-negative was defined as both tests being negative). The solid scintillation 14C-UBT involves a scintillation sampling bottle and a 14C-urea capsule. The sampling bottle contains a stack of carbon dioxide-absorbing and scintillation sheets. The test is read using a photomultiplier. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for H pylori infection were evaluated. This study enrolled 239 participants. There were 98 males and 141 females, aged 45.8 ±â€…11.9 (range: 21-66) years. Thirty-four participants were excluded due to a discrepancy between the rapid urease test and immunohistochemistry examination. Finally, 205 participants were included in the analysis. According to the gold standard, 87 out of 205 (42.4%) participants were H pylori-positive. Compared with the gold standard, the sensitivity, specificity, accuracy, and positive and negative predictive values of the solid scintillation 14C-UBT were 95.4%, 97.5%, 96.6%, 96.5%, and 96.6% for the solid scintillation UBT, respectively. One participant experienced 1 adverse event (AE) (exacerbation of chronic cholecystitis), and the AE eventually improved by itself. The investigators determined that the AE was unrelated to the study device. The noninvasive solid scintillation 14C-UBT has a high diagnostic value for H pylori infection, comparable to the diagnostic value of the gold standard.

Identification of a Novel Protein-Based Prognostic Model in Gastric Cancers.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. However, there are still no reliable biomarkers for the prognosis of this disease. This study aims to construct a robust protein-based prognostic prediction model for GC patients. The protein expression data and clinical information of GC patients were downloaded from the TCPA and TCGA databases, and the expressions of 218 proteins in 352 GC patients were analyzed using bioinformatics methods. Additionally, Kaplan-Meier (KM) survival analysis and univariate and multivariate Cox regression analysis were applied to screen the prognosis-related proteins for establishing the prognostic prediction risk model. Finally, five proteins, including NDRG1_pT346, SYK, P90RSK, TIGAR, and XBP1, were related to the risk prognosis of gastric cancer and were selected for model construction. Furthermore, a significant trend toward worse survival was found in the high-risk group (p = 1.495 × 10-7). The time-dependent ROC analysis indicated that the model had better specificity and sensitivity compared to the clinical features at 1, 2, and 3 years (AUC = 0.685, 0.673, and 0.665, respectively). Notably, the independent prognostic analysis results revealed that the model was an independent prognostic factor for GC patients. In conclusion, the robust protein-based model based on five proteins was established, and its potential benefits in the prognostic prediction of GC patients were demonstrated.

Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial.

Background: Helicobacter pylori (H. pylori) eradication has been reported to cause short-term disruption of gut microbiota. It is acknowledged that probiotics supplementation mitigates side effects induced by H. pylori eradication, yet its role on alleviating dysbiosis of microbiota is obscure. Objectives: To evaluate the impact of probiotics on gastrointestinal microbiota after eradication therapy. Methods: This was a multicenter, double-blinded, randomized trial done at seven centers in China. A total of 276 treatment-naïve H. pylori-positive patients were randomly assigned to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, furazolidone) combined with probiotics (Bifidobacterium Tetragenous viable Bacteria Tablets) (n=140) or placebo (n=136) for 28 days. Saliva, gastric mucosa and fecal samples were collected before and after therapy for 16S rRNA gene sequencing. Results: The incidence of gastrointestinal adverse events was lower in probiotics group compared to placebo group (23.6% vs 37.7%, p=0.016), while there was no significant difference in eradication rate. We found dramatic perturbations of gut microbiota immediately following eradication, with the predominance of Proteobacteria in replacement of commensal Firmicutes and Bacteroidetes, and gradually restored after two weeks. The reduction of gut Bacteroidetes caused by eradication drugs was neutralized with probiotics supplementation. The gastric microbiota was completely reconstituted with H. pylori depleted and other taxa flourished. Of note, patients treated with probiotics showed smaller fluctuations of gastric microbiota compared to those with placebo. We also observed changes of saliva microbiota after H. pylori eradication, illustrated by the overgrowth of Neisseria and depletion of Streptococcus. The expansion of some pathogenic genera, including Porphyromonas, Leptotrichia, in the mouth was suppressed by probiotics. Conclusion: This study not only demonstrated the beneficial effect of probiotics implementation on side events during H. pylori eradication but also provided a comprehensive profile of microbiome alterations along gastrointestinal tract that modulated by probiotics.

CC Chemokine Ligand-2: A Promising Target for Overcoming Anticancer Drug Resistance.

CC chemokine ligand-2 (CCL2), a proinflammatory chemokine that mediates chemotaxis of multiple immune cells, plays a crucial role in the tumor microenvironment (TME) and promotes tumorigenesis and development. Recently, accumulating evidence has indicated that CCL2 contributes to the development of drug resistance to a broad spectrum of anticancer agents, including chemotherapy, hormone therapy, targeted therapy, and immunotherapy. It has been reported that CCL2 can reduce tumor sensitivity to drugs by inhibiting drug-induced apoptosis, antiangiogenesis, and antitumor immunity. In this review, we mainly focus on elucidating the relationship between CCL2 and resistance as well as the underlying mechanisms. A comprehensive understanding of the role and mechanism of CCL2 in anticancer drug resistance may provide new therapeutic targets for reversing cancer resistance.

AMP-activated protein kinase ß1 or ß2 deletion enhances colon cancer cell growth and tumorigenesis.

Abnormal metabolism is a major hallmark of cancer and has been validated as a therapeutic target. Adenine monophosphate-activated protein kinase (AMPK), an αßγ heterotrimer, performs essential functions in cancer progression due to its central role in maintaining the homeostasis of cellular energy. While the contributions of AMPKα and AMPKγ subunits to cancer development have been established, specific roles of AMPKß1 and AMPKß2 isoforms in cancer development are poorly understood. Here, we show the functions of AMPKß1 and AMPKß2 in colon cancer. Specifically, deletion of AMPKß1 or AMPKß2 leads to increased cell proliferation, colony formation, migration, and tumorigenesis in HCT116 and HT29 colon cancer cells. Interestingly, the AMPKß1 and AMPKß2 isoforms have slightly different effects on regulating cancer metabolism, as colon cancer cells with AMPKß1 knockout showed decreased rates of glycolysis-related oxygen consumption, while AMPKß2 deletion led to enhanced rates of oxygen consumption due to oxidative phosphorylation. These results demonstrate that functional AMPKß1 and AMPKß2 inhibit growth and tumorigenesis in colon cancer cells, suggesting their potential as effective targets for colon cancer therapy.

The Effects of Different Induction Chemotherapy Cycles and Adjuvant Chemotherapy on the Survival Outcomes of Patients With Locally Advanced Nasopharyngeal Carcinoma.

Objective: This study investigated whether differences in the induction chemotherapy (IC) cycle number and adjuvant chemotherapy (AC) affect survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: The survival outcomes of 386 consecutive LA-NPC patients treated between January 2015 and March 2018 were retrospectively analyzed. Univariate and multivariate analyses were used to compare treatment groups defined by IC< 3 or ≥3 IC cycles followed by radiotherapy with or without AC (i.e., IC<3+AC, IC<3+non-AC, IC≥3+AC, and IC≥3+non-AC groups). Results: The median follow-up time was 53 months (range: 2-74 months) and the median number of IC cycles was 2 (range: 1-6 cycles). The 3-year overall survival (OS) rate was significantly higher in patients with IC≥3 cycles compared to IC<3 cycles (95.7% vs. 90.3%, P=0.020). Multivariate analysis indicated that the IC cycle number is an independent factor for OS (hazard ratio=0.326, P=0.007). Furthermore, patients in the IC<3+AC group had a better OS rate than those in the IC<3+non-AC group (91.6% vs. 79.1%, P=0.030), indicating that AC positively affected OS in patients with IC<3. However, no significant difference in the OS rate was found between IC≥3+non-AC and IC≥3+AC groups (92.1% vs. 94.6%, P =0.550). Conclusion: The IC cycle number appears to be an independent prognostic factor for higher OS in LA-NPC patients who received ≥3 cycles. Sequential AC after IC plus radiotherapy may improve OS in patients with IC<3 cycles.

LINC00514 facilitates cell proliferation, migration, invasion, and epithelial-mesenchymal transition in non-small cell lung cancer by acting on the Wnt/ß-catenin signaling pathway.

The long non-coding RNA (lncRNA) LINC00514 was identified to play an essential oncogenic function in different human cancers, but its effects in non-small cell lung cancer (NSCLC) are yet to be elucidated. In this study, we evaluated the function of LINC00514 in NSCLC. LINC00514 expression and prognosis in NSCLC were analyzed using qRT-PCR and online bioinformatic tools. The bioeffects of LINC0514 in NSCLC cells were examined using cell counting kit-8, colony formation, and transwell assays. Western blotting was used to measure the expression of the target proteins. The LINC00514 regulation of the Wnt/ß-catenin signaling pathway was assessed using a specific agonist (LiCl) and luciferase reporter assay. We found that LINC00514 expression was elevated in NSCLC cells and clinical samples and that increased LINC00514 expression predicted poorer patient prognosis. Silencing LINC00514 suppresses proliferation, migration, and invasion of NSCLC cells. Downregulation of LINC00514 inhibited Wnt/ß-catenin signaling and epithelial-mesenchymal transition (EMT). Moreover, suppression of the biological phenotypes of NSCLC cells induced by LINC00514 gene silencing was restored after LiCl treatment. Finally, we found that silencing LINC00514 attenuated the growth of xenograft tumors in vivo. Altogether, this study provides the latest convincing evidence that LINC00514 facilitates the malignant biological behavior of NSCLC cells through activation of the Wnt/ß-catenin pathway, which might offer a beneficial approach for the treatment of NSCLC.

Nosocomial transmission and rearrangement of large resistance-virulence hybrid plasmids between two bacteremic ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae strains with low fitness cost.

OBJECTIVES: To characterize nosocomial transmission and rearrangement of the resistance-virulence plasmid between two ST11-K64 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strains (JX-CR-hvKP-10 and JX-CR-hvKP-9) with low fitness. METHODS: Phenotypic tests were used to assess the virulence of JX-CR-hvKP-10 and JX-CR-hvKP-9. Whole-genome sequencing was used to analyze JX-CR-hvKP-10 and JX-CR-hvKP-9 chromosomes and plasmids. Fitness and conjugation experiments were also conducted using these two CR-hvKP isolates. RESULTS: Phenotypic tests indicated that both JX-CR-hvKP-10 and JX-CR-hvKP-9 were multidrug-resistant and hypervirulent K. pneumoniae. Whole-genome sequencing and clinical information demonstrated that the super large resistance-virulence fusion plasmid pJX10-1 formed precisely by the fusion of pJX9-1 and pJX9-2 via the nosocomial transmission. Interestingly pJX9-1 itself was also a classic resistance-virulence fusion plasmid by way of the blaKPC-carrying resistance plasmid and pLVPK-like virulence plasmid. Compared with classic K. pneumoniae ATCC700603, fitness analysis revealed no significant difference in growth was observed between JX-CR-hvKP-10 and JX-CR-hvKP-9. CONCLUSION: Nosocomial transmission and rearrangement of a blaKPC-harboring plasmid and a pLVPK-like virulence plasmid with a low fitness cost in ST11 K. pneumoniae enhances drug resistance and virulence simultaneously. Thus, active surveillance of this hybrid plasmid is needed to prevent these efficient resistance-virulence plasmids from disseminating in hospital settings.

A Dual-Responsive Platform Based on Antifouling Dendrimer-CuS Nanohybrids for Enhanced Tumor Delivery and Combination Therapy.

Design of stimuli-responsive nanomedicine with enhanced tumor delivery for combination therapy still remains a great challenge. Here, a unique design of an antifouling-dendrimer-based nanoplatform with dual pH- and redox-responsiveness is reported to meet this challenge. First, generation 5 (G5) poly(amidoamine) dendrimers are modified with targeting ligand cyclic arginine-glycine-aspartic acid (RGD) peptide through a polyethylene glycol (PEG) spacer and zwitterion of thiolated N,N-dimethyl-cysteamine-carboxybetaine (CBT) via pH-responsive benzoicimine bond to form G5.NH2 PEGRGDCBT conjugates. Then, doxorubicin (DOX) is linked to the functional G5 dendrimers through a redox-responsive disulfide bond, followed by entrapment of CuS nanoparticles within the dendrimers. The created functional dendrimer-CuS nanohybrids with a CuS core size of 3.6 nm display a good antifouling property and excellent photothermal conversion property in the second near-infrared window. In addition, the neutral surface charge of the nanohybrids is able to be switched to be positive in the tumor region with slightly acidic microenvironment due to the break of benzoicimine bond to promote their intracellular uptake, while the redox-sensitive disulfide bond affords the fast release of the conjugated DOX within tumor cells to exert its therapeutic effect. Taken together with the CuS cores, the created dendrimer-CuS nanohybrids enable enhanced combination chemotherapy and photothermal therapy of tumors.

Prevalence of the NTEKPC-I on IncF Plasmids Among Hypervirulent Klebsiella pneumoniae Isolates in Jiangxi Province, South China.

Infection caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has become a tricky health care threat in China and KPC-2 enzyme is a main factor mediating resistance to carbapenems of K. pneumoniae. Here, we report the characterization of the genetic environment of the blaKPC-2 gene in CR-hvKP clinical isolates from South China. Forty-five non-duplicated CR-hvKP isolates collected in Jiangxi Province from 2018 to 2019 were analyzed. Each of them were multidrug-resistant due to the presence not only of blaKPC-2 gene but also of other resistance determinants, including Metallo-ß-lactamases (NDM-1), extended-spectrum ß-lactamases (TEM-1, CTX-M-14, SHV-1), and plasmid-mediated quinolone resistance determinants (qnrS, aac(6')-Ib-cr). After plasmid analyses of PCR-based replicon typing (PBRT), mapping PCR, amplicon sequencing, and whole-genome sequencing (WGS) were used to analyze the genetic environment of the blaKPC-2 gene. PCR analysis of pLVPK-like plasmids, Southern Blot, and mouse lethality assay were used to characterize the virulence phenotype of K. pneumoniae. Multilocus sequence typing (MLST) analysis showed ST11 CR-hvKP was the predominant clone. In conclusion, this is the first analysis of diverse genetic structures blaKPC-2 gene in CR-hvKP isolates from south China. Both the NTEKPC-I on the IncF plasmids and pLVPK-like virulence plasmids make contributions to the formation of CR-hvKP especially ST11 which need more attention.

Antifouling Dendrimer-Entrapped Copper Sulfide Nanoparticles Enable Photoacoustic Imaging-Guided Targeted Combination Therapy of Tumors and Tumor Metastasis.

The development of functional intelligent theranostic nanoplatform for imaging-directed synchronous inhibition of primary tumor and tumor metastasis is still a challenging task. We present here the creation of functional dendrimer-entrapped CuS nanoparticles (CuS DENPs) complexed with plasmid DNA-encoding hypermethylation in cancer 1 (pDNA-HIC1) for photoacoustic (PA) imaging-directed simultaneous inhibition of tumors and tumor metastasis. Poly(amidoamine) dendrimers of generation 5 were covalently attached with 1,3-propane sultone and arginine-glycine-aspartic acid (RGD) peptide through a spacer of poly(ethylene glycol) and adopted for the templated synthesis of CuS NPs. The prepared functional RGD-CuS DENPs possess a mean CuS core diameter of 4.2 nm, good colloidal stability, and an excellent absorption feature in the second near-infrared window, thus having a photothermal conversion efficiency of 49.8% and an outstanding PA imaging capability. The functional DENPs can effectively deliver pDNA-HIC1 to prevent cancer cell invasion and metastasis in a serum-enhancing manner by virtue of zwitterionic modification-rendered antifouling property. The developed RGD-CuS DENPs/pDNA polyplexes display αvß3 integrin-targeted enhanced anticancer activity through the combined CuS NP-mediated photothermal therapy (PTT) and pDNA delivery-rendered cancer cell metastasis inhibition. This can also be proven by the therapeutic efficacy of a triple-negative breast cancer model in vivo, where inhibition of both the primary subcutaneous tumor and lung metastasis can be realized. The created dendrimer-CuS hybrid nanoplatform represents one of the updated designs of nanomedicine for PA imaging-directed combination PTT/gene therapy of tumors and tumor metastasis.

Silver nanoprism-based plasmonic ELISA for sensitive detection of fluoroquinolones.

Fluoroquinolones are synthetic antibiotics that are commonly used in animal husbandry, and the consumption of animal products with fluoroquinolone residues has imposed a serious threat to human health. Here, we report a plasmonic enzyme-linked immunosorbent assay (pELISA) method based on oxidative etching of silver nanoprisms (AgNPRs) for the quantitative and qualitative detection of danofloxacin (DAN), a fluoroquinolone antibiotic. AgNPRs that undergo colorimetric changes upon oxidative etching by H2O2 serve as the signal transducer in our design. An indirect competitive pELISA was constructed by introducing biotinylated monoclonal antibody (mAb), streptavidin and biotinylated glucose oxidase, which catalyzes the generation of H2O2 for etching AgNPRs. The quantitative detection limit of the proposed method was 0.24 ng mL-1 for DAN. The qualitative detection limit for DAN reached 0.32 ng mL-1, which was 32-fold lower than that of the assay using 3,3',5,5'-tetramethylbenzidine (TMB) as the signal transducer. The average recoveries of DAN in milk ranged from 103% to 121%, with a coefficient of variation of 0.6-3.41%. The recovery results were further confirmed using liquid chromatography-tandem mass spectrometry. In summary, the proposed AgNPR-etching pELISA exhibits high sensitivity, good accuracy and excellent reliability for the quantitative and qualitative detection of DAN in milk.

Characterization of zwitterion-modified poly(amidoamine) dendrimers in aqueous solution via a thorough NMR investigation.

Zwitterions are a class of unique molecules that can be modified onto nanomaterials to render them with antifouling properties. Here we report a thorough NMR investigation of dendrimers modified with zwitterions in terms of their structure, hydrodynamic size, and diffusion time in aqueous solution. In this present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were partially decorated with carboxybetaine acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively with different modification degrees. The formed zwitterion-modified G5 dendrimers were characterized using NMR techniques. We show that the zwitterion modification leads to increased G5 dendrimer size in aqueous solution, suggesting that the modified zwitterions can form a hydration layer on the surface of G5 dendrimers. In addition, the hydrodynamic sizes of G5 dendrimers modified with different zwitterions but with the same degree of surface modification are discrepant depending on the type of zwitterions. The present study provides a new physical insight into the structure of zwitterion-modified G5 dendrimers by NMR techniques, which is beneficial for further design of different biomedical applications.

Preparation of an Antidanofloxacin Monoclonal Antibody and Development of Immunoassays for Detecting Danofloxacin in Meat.

Danofloxacin (DAF), a third-generation fluroquinolone (FQ), is widely used as a broad-spectrum antibacterial drug to prevent diseases in livestock and poultry. In this study, a highly specific and sensitive monoclonal antibody (mAb) against DAF was prepared. Also, the mAb was used for the indirect competitive enzyme-linked immunosorbent assay (icELISA) and immunochromatographic strip for the detection of DAF residues in meat. The IC50 of the icELISA based on this mAb was 1.39 ng/mL, and the limit of detection was 0.2 ng/mL. According to the cross-reactivity (CR) experiment, the ELISA that we developed was highly specific and had low CR with other FQ analogues. Moreover, the cut-off of the immunochromatographic strip developed for detecting DAF in meat was 5 ng/mL. Overall, the developed ELISA and immunochromatographic strip based on the prepared mAb were proved reliable for the rapid detection of DAF in meat and can be considered as effective screening methods for food safety and quality management.

Zwitterion-functionalized dendrimer-entrapped gold nanoparticles for serum-enhanced gene delivery to inhibit cancer cell metastasis.

We demonstrate a novel serum-enhanced gene delivery approach using zwitterion-functionalized dendrimer-entrapped gold nanoparticles (Au DENPs) as a non-viral vector for inhibition of cancer cell metastasis in vitro. Poly(amidoamine) dendrimers of generation 5 decorated with zwitterion carboxybetaine acrylamide (CBAA) and lysosome-targeting agent morpholine (Mor) were utilized to entrap gold NPs. We show that both Mor-modified and Mor-free Au DENPs are cytocompatible and can effectively deliver plasmid DNA encoding different reporter genes to cancer cells in medium with or without serum. Strikingly, due to the antifouling property exerted by the attached zwitterion CBAA, the gene delivery efficiency of Mor-modified Au DENPs and the Mor-free Au DENPs in the serum-containing medium are 1.4 and 1.7 times higher than the corresponding vector in serum-free medium, respectively. In addition, the Mor-free vector has a better gene expression efficiency than the Mor-modified one although the Mor modification enables the polyplexes to have enhanced cancer cell uptake. Wound healing and hypermethylated in cancer 1 (HIC1) protein expression assay data reveal that the expression of HIC1 gene in cancer cells enables effective inhibition of cell migration. Our findings suggest that the created zwitterion-functionalized Au DENPs may be employed as a powerful vector for serum-enhanced gene therapy of different diseases. STATEMENT OF SIGNIFICANCE: One major challenge in the non-viral gene delivery system is that the strong interaction between serum protein and the positively charged vector/gene polyplexes neutralize the positive charge of the polyplexes and form possible protein corona, thereby significantly reducing their cellular uptake efficiency and subsequent gene transfection outcome. Here we demonstrate the conceptual advances in the serum-enhanced gene delivery using zwitterionic modification of polycationic poly(amidoamine) (PAMAM) dendrimer-entrapped gold nanoparticles (Au DENPs). We demonstrate that partial zwitterionic modification of Au DENPs is able to confer them with antifouling property to resist serum protein adsorption. Hence the vector/DNA polyplexes are able to maintain their positive potentials and small hydrodynamic size in the serum environment, where serum solely play the role as a nutrition factor for enhanced gene delivery. We demonstrate that partial modification of zwitterion carboxybetaine acrylamide (CBAA) and morpholine (Mor) onto the surface Au DENPs renders the vector with both antifouling property and lysosome targeting ability, respectively. The generated functional Au DENPs can compact pDNA to form polyplexes that enable serum-enhanced gene expression. In particular, once complexed with hypermethylated in cancer 1 (HIC1) gene, the polyplexes can significantly inhibit cancer cell migration and metastasis.

Zwitterionic Modification of Nanomaterials for Improved Diagnosis of Cancer Cells.

Nanomaterials have been ubiquitously employed as platforms to load imaging agents for cancer diagnosis. In general, the majority of nanomaterials are accumulated in the reticuloendothelial system (RES)-associated organs such as liver, spleen, and lung after systemic administration. Although the adopted strategy used to modify nanomaterials with polyethylene glycol (PEG) has relieved this problem to some extent, challenges still remain for further clinical applications. Recently, nanomaterials with zwitterionic surface modification have been found to have a better antifouling property than those with PEGylation modification. This Topical Review reports the recent progress in the development of zwitterion-modified nanomaterials for improved cancer cell diagnosis, including zwitterionic modification of hybrid nanoparticles for enhanced fluorescence, computed tomography (CT), magnetic resonance (MR), and dual-mode imaging of cancer cells, and the zwitterionic modification of nanofibers for specific capture of circulating tumor cells with improved capture purity and efficiency. Challenges and future perspectives in this particular field are also discussed.

Effectiveness and safety of furazolidone-containing quadruple regimens in patients with Helicobacter pylori infection in real-world practice.

BACKGROUND & AIMS: The eradication rate of Helicobacter pylori (H pylori) has decreased largely because of the antibiotic resistance. We aimed to evaluate the effectiveness and safety of furazolidone-containing quadruple regimens for H pylori eradication. METHODS: This was an observational study of furazolidone-containing quadruple regimens for H pylori infection in real-world settings. Data sets were collected from the medical records and telephone interviews of patients referred to a specialist clinic for suspected H pylori reinfection from January 1, 2015, to January 1, 2018, at the First Affiliated Hospital of Nanchang University. Main outcome measures were the eradication rate and adverse reactions during medication. RESULTS: Among 584 patients with H pylori infection that met the inclusion criteria, 561 (96.1%) were treated for the first time, 19 (3.3%) had one, and 4 (0.5%) had two or more prior to furazolidone-containing quadruple regimens. The eradication rates for 10-day and 14-day regimens were 93.7% (95% CI: 91.5%-95.9%) vs 98.2% (95% CI: 95.6%-99.3%), respectively (P = 0.098). Adverse drug reactions occurred in 8.2% (48/584) with abdominal discomfort being the most common symptom. Overall adverse events with 10-day regimens were lower than 14-day regimens (6.1% vs 17.4%, P < 0.001). Logistic regression analysis indicated that poor adherence (adjusted odds ratio [AOR] = 46.5, 95% CI: 9.7-222.4) was correlated with failed eradication. Adverse drug reactions during medication were related to smoking and tobacco status, alcohol intake history, regimens combined with tetracycline, and poor adherence (all P < 0.05). CONCLUSIONS: Furazolidone-containing quadruple regimens proved both safe and highly effective in a real-world setting.

Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis.

Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r1 relaxivity (13.17 mM s-1), acceptable cytocompatibility, and targeting specificity to αvß3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

Downregulation of tumor suppressor RACK1 by Helicobacter pylori infection promotes gastric carcinogenesis through the integrin ß-1/NF-κB signaling pathway.

Receptor of activated protein kinase C 1 (RACK1) is downregulated in gastric cancer and is involved in modulating NF-κB signaling pathway activity. However, the underlying molecular mechanisms regulating RACK1 expression are unclear. In this study, we demonstrated that downregulated expression of RACK1 was observed in gastric cancer tissue compared to adjacent normal tissue and was correlated with poor prognosis in patients. Helicobacter pylori (H. pylori) infection downregulated RACK1 expression in concert with canonical NF-κB signaling pathway activation in vivo and in vitro. RACK1 overexpression suppressed NF-κB signaling pathway activation as well as the release of downstream proinflammatory cytokines. In addition, RACK1 downregulation increased integrin ß-1 expression, while integrin ß-1 silencing decreased NF-κB signaling activation. Moreover, H. pylori infection downregulated RACK1 but upregulated integrin ß-1 expression at the precancerous lesion stages in human subjects. Our data indicate that H. pylori infection promotes the upregulation of integrin ß-1 expression via downregulation of RACK1 expression, which subsequently leads to the elevated activation of the NF-κB signaling pathway, an essential step in H. pylori-induced carcinogenesis.

Sensitive and Matrix-Tolerant Lateral Flow Immunoassay Based on Fluorescent Magnetic Nanobeads for the Detection of Clenbuterol in Swine Urine.

The lack of sensitivity and poor matrix tolerance are the main bottlenecks of the lateral flow immunoassay (LFIA). Here, a sensitive and matrix-tolerant method that integrated immunomagnetic separation and fluorescent lateral flow immunoassay (IMS-FLFIA) based on fluorescent magnetic nanobeads was developed to detect the clenbuterol (CLE) residue in swine urine. The limit of detection (LOD) of IMS-FLFIA is 4 times lower than that of traditional colloidal gold LFIA. This method, which exhibits similar LOD and linearity range in both phosphate-buffered saline and urine swine, is highly correlated with liquid chromatography-tandem mass spectrometry for the detection of real swine urine samples. The result indicated that IMS-FLFIA has a universal resistance to the swine urine matrix. The merits of this assay, high sensitivity, matrix tolerance, accuracy, and specificity, ensure a promising future in detection of veterinary drug residues.