Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

Objective To investigated the effect of stenosis characteristics (vascular elasticity and plaque properties) on myocardial ischemia. Methods An ideal geometric multi-scale coronary stenosis model based on fluid-structure interaction was established, and the fractional flow reserve (FFR) was simulated to evaluate myocardial ischemia. The effects of vascular elastic wall (elastic modulus of 1 MPa) and rigid wall, plaque types (lipid-rich plaque and calcified plaque) and plaque volume on myocardial ischemia were considered separately. Results The FFRCT simulation result of vessels with elastic wall was larger than that with rigid wall under all stenosis situations. The FFRCT of vessels in lipid-rich lesions was higher than that of calcified plaque (P=0.001). The trapezoidal plaque volume was larger than the cosine plaque volume, and the FFRCT of vessels in trapezoidal plaque was smaller than that of cosine plaque (P=0.001). Conclusions Vascular elasticity is a critical factor to simulate vascular hemodynamics. In moderate stenosis, calcified plaques are more likely to induce myocardial ischemia due to the larger luminal deformation and dilation of rich lipid plaque. When the stenosis is constant, the smaller the plaque volume, the higher the FFRCT and the smaller the possibility of myocardial ischemia.

Antimicrobial resistance is a common problem in both veterinary and human medicine. The increasing incidence of multi-drug resistance and even pan-drug resistance is posing serious threat to public health and food safety. This review aimed to present an updated overview on antimicrobial resistance, covering the transmission mechanisms and its potential controlling strategies.

A growing body of diversified antibiotic resistances raises a significant challenge to anti-infection clinical therapeutics. The emergence of superbugs carrying MCR-1/2 or NDM-1 determinants underlines the importance and urgency in elucidation of molecular mechanisms shared by antibiotic resistances. It is aware that different classes of bactericidal antibiotics consistently stimulate the production of deleterious reactive oxygen species (ROS), which are accompanied with metabolic disturbance. The different destinations of ROS determine its consequence on bacterial fate. Here, we review antibiotic-induced production, progression and transformation of ROS, as well as its role in the development of antibiotic resistance. Additionally, we anticipate that mesosome-like structures-aided exclusion of hydrogen peroxide might represent a previously-unknown mechanism for antibiotic resistance. This mini-review is aiming to present an update overview on antibiotic resistance and provide clues to the development of novel antibiotics.

A growing body of diversified antibiotic resistances raises a significant challenge to anti-infection clinical therapeutics.The emergence of superbugs carrying MCR-1/2 or NDM-1 determinants underlines the importance and urgency in elucidation of molecular mechanisms shared by antibiotic resistances.It is aware that different classes of bactericidal antibiotics consistently stimulate the production of deleterious reactive oxygen species (ROS), which are accompanied with metabolic disturbance. The different destinations of ROS determine its consequence on bacterial fate. Here, we review antibiotic-induced production,progression and transformation of ROS,as well as its role in the development of antibiotic resistance. Additionally, we anticipate that mesosome-like structures-aided exclusion of hydrogen peroxide might represent a previously-unknown mechanism for antibiotic resistance. This mini-review is aiming to present an update overview on antibiotic resistance and provide clues to the development of novel antibiotics.

A growing body of diversified antibiotic resistances raises a significant challenge to anti-infection clinical therapeutics.The emergence of superbugs carrying MCR-1/2 or NDM-1 determinants underlines the importance and urgency in elucidation of molecular mechanisms shared by antibiotic resistances.It is aware that different classes of bactericidal antibiotics consistently stimulate the production of deleterious reactive oxygen species (ROS), which are accompanied with metabolic disturbance. The different destinations of ROS determine its consequence on bacterial fate. Here, we review antibiotic-induced production,progression and transformation of ROS,as well as its role in the development of antibiotic resistance. Additionally, we anticipate that mesosome-like structures-aided exclusion of hydrogen peroxide might represent a previously-unknown mechanism for antibiotic resistance. This mini-review is aiming to present an update overview on antibiotic resistance and provide clues to the development of novel antibiotics.

Objective To investigate the diagnostic value of multiparametric MRI in early prostate cancer(PCa) based on PI-RADS version 2.Methods 27 surgically-proved early PCa patients were collected in this retrospective study.T2WI,DWI and DCE were evaluated by two blinded radiologists.By 12 sub-region classification method the possibility of the presence of cancer at each sub-region was scored according to the PI-RADS V2.The receiver operating characteristic (ROC) curve was used to analyze the diagnosic efficacy of the following 4 protocols:T2WI alone(protocol 1),T2WI+DWI(protocol 2),T2WI+DCE(protocol 3),T2WI+DWI+DCE(protocol 4).The sensitivity,specificity and accuracy for each protocol were calculated.The average scores of cancerous sub-regions and non-cancerous sub-regions were calculated and the independent sample t test was used to compare the four protocols.Results 324 sub-regions were analyzed in 27 early PCa patients and then divided into 119 cancerous sub-regions and 205 non-cancerous sub-regions,including 64 peripheral zone cancerous sub-regions and transition zone cancerous sub-regions.In protocol 1-4, the average scores of cancerous sub-regions in orderwere 3.13±1.19,3.27±1.15,3.28±1.23, 3.33±1.16,respectively.Non-cancerous sub-regions's scores in order were 1.98±0.90,1.91±0.91, 2.03±0.99,1.94±0.96 respectively and there were significant differences among each protocol (P<0.05).The area under the ROC curve of the 4 protocols for region-based analysis were displayed in descending order: protocol 4 (0.819), protocol 2 (0.810), protocol 3 (0.772), protocol 1 (0.765) and there were no significant differences between any two protocols (P>0.05).In four protocols, the sensitivity in order were 45.40%, 56.30%, 59.70%, 61.34%, while the specificity in order were 95.10%, 96.10%, 89.80%, 96.60%, and the accuracy in order were 76.85%, 81.48%, 78.70%, 83.65%.Conclusion Multiparametric MRI can improve the diagnostic accuracy for the detection of early PCa, and T2WI+DWI+DCE is with the highest value.The PI-RADS V2 system is a better semi quantitative method for evaluation of early PCa.

Objective To evaluate the value of T2WI scores for diagnosis and differential diagnosis of transition zone prostate cancer(PCa).Methods T2WI of 43 cases of transition zone PCa and 91 cases of benign prostatic hyperplasia(BPH) were analyzed retrospectively.Transition zone T2WI signs were divided into the main signs and the secondary signs, which were given different scores and were evaluated separately by receiver operating characteristic (ROC) curve for their diagnostic value.Results In a total of 11 scores sections (-1-10), as the increase of scores, the sensitivity of transition zone PCa was decreased while the specificity and positive predictive value were both increased.According to the ROC curve, when the critical value of scores≥4.5, the sensitivity, specificity, negative predictive value, and the accuracy were 81%,73.3%,90.9%,70.4% respectively.When the scores ≥8.5,the specificity and positive predictive value were both 100%.When the scores ≥0.5 and ≥1.5,the negative predictive value were 100%.Conclusion T2WI scores can quantitatively analyze the transition zone PCa,which has an important value to improve the clinical diagnosis and guide treatment.

The Escherichia coli fadR protein product, a paradigm/prototypical FadR regulator, positively regulates fabA and fabB, the two critical genes for unsaturated fatty acid (UFA) biosynthesis. However the scenario in the other Ɣ-proteobacteria, such as Shewanella with the marine origin, is unusual in that Rodionov and coworkers predicted that only fabA (not fabB) has a binding site for FadR protein. It raised the possibility of fad regulon contraction. Here we report that this is the case. Sequence alignment of the FadR homologs revealed that the N-terminal DNA-binding domain exhibited remarkable similarity, whereas the ligand-accepting motif at C-terminus is relatively-less conserved. The FadR homologue of S. oneidensis (referred to FadR_she) was over-expressed and purified to homogeneity. Integrative evidence obtained by FPLC (fast protein liquid chromatography) and chemical cross-linking analyses elucidated that FadR_she protein can dimerize in solution, whose identity was determined by MALDI-TOF-MS. In vitro data from electrophoretic mobility shift assays suggested that FadR_she is almost functionally-exchangeable/equivalent to E. coli FadR (FadR_ec) in the ability of binding the E. coli fabA (and fabB) promoters. In an agreement with that of E. coli fabA, S. oneidensis fabA promoter bound both FadR_she and FadR_ec, and was disassociated specifically with the FadR regulatory protein upon the addition of long-chain acyl-CoA thioesters. To monitor in vivo effect exerted by FadR on Shewanella fabA expression, the native promoter of S. oneidensis fabA was fused to a LacZ reporter gene to engineer a chromosome fabA-lacZ transcriptional fusion in E. coli. As anticipated, the removal of fadR gene gave about 2-fold decrement of Shewanella fabA expression by β-gal activity, which is almost identical to the inhibitory level by the addition of oleate. Therefore, we concluded that fabA is contracted to be the only one member of fad regulon in the context of fatty acid synthesis in the marine bacteria Shewanella genus.
Amino Acid Sequence ; Bacterial Proteins ; chemistry ; metabolism ; Base Sequence ; Binding Sites ; DNA, Bacterial ; metabolism ; Escherichia coli ; genetics ; metabolism ; Fatty Acid Synthase, Type II ; genetics ; metabolism ; Fatty Acids ; biosynthesis ; Gene Expression Regulation, Bacterial ; drug effects ; Molecular Sequence Data ; Oleic Acid ; pharmacology ; Protein Binding ; drug effects ; Regulon ; genetics ; Repressor Proteins ; chemistry ; metabolism ; Shewanella ; genetics ; metabolism

Objective To compose and evaluate anti‐tumor activities of 3‐substituted indole‐2‐one compounds which may have dual inhibitory activities against both tubulin protein and VEGFR‐2 tyrosine kinase .Methods Target compounds were prepared starting from substituted aniline viacondensation ,cyclization and reduction .Results 11 target compounds were syn‐thesized and all the compounds displayed moderate anti‐proliferative activities against three tumor cell lines .Compound j9 showed a certain inhibitory activity against both VEGFR‐2 kinase and tubulin protein in vitro .Conclusion This series of indo‐lin‐2‐one derivatives were found to be a novel kind of multi‐target inhibitor .