Double paths network with residual information distillation for improving lung CT image super resolution.

OBJECTIVE: Medical image analysis is particularly important for doctors to differential diagnosis of diseases. Due to the outbreak of COVID-19, how to diagnose COVID-19 accurately has become a key issue. High-resolution lung CT images can provide more diagnostic information, so there is an urgent need to develop a super-resolution method to improve the resolution of medical images. METHODS: In this paper, a method based on double paths with residual information distillation for medical images super resolution (DRIDSR) is established. In the low-frequency path, shallow convolutional network is used to get low-frequency features, while in the high-frequency path, a residual information distillation module (RIDM) is designed to obtain clearer high-frequency features. RIDM cascades multiple residual blocks, and uses the output of each residual block as the input of IDB for further information distillation. Finally, it merges the information left by multiple IDBs as output. RESULTS: The proposed method is tested on the public dataset COVID-CT. The DRIDSR reconstruction quality of the algorithm is higher than that of the SRCNN, ESPCN, VDSR, IMDN and PAN method (+2.21 dB, +2.41 dB, +1.42 dB, +0.43 dB, +0.54 dB improvement, respectively) at × 3 upscale factor and (+2.35 dB, +2.17 dB, +1.59 dB, +0.48 dB, +0.56 dB increase, respectively) at ×4 upscale factor. While the number of parameters and analysis time of our model are reduced. CONCLUSIONS: It is demonstrated that DRIDSR network can obtain better performance and better HR medical images than several state-of-the-art SR methods in terms of objective indicators and subjective evaluation.

Combined effect of Polymyxin B and Tigecycline to overcome Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae.

We assessed the prevalence of polymyxin B (PMB)- and tigecycline (TGC)-heteroresistant Klebsiella pneumoniae isolates and investigated the combined effect of PMB and TGC against dual-heteroresistant K. pneumoniae. Ninety-five nonduplicated carbapenem-resistant K. pneumoniae (CRKP) clinical isolates were collected from a tertiary-care teaching hospital in China. PCR was used to detect the resistant genes among the CRKP isolates. Population analysis profiling (PAP) was carried out to evaluate the existence of heteroresistance. A time-kill assay of PMB combined with TGC was conducted against heteroresistant K. pneumoniae strains. Real-time PCR was performed to determine the pmrA, phoP, and acrB expression levels. Among them, 74 isolates (77.9%) were susceptible to TGC, and 90 isolates (94.7%) were susceptible to PMB. In addition, of the TGC-susceptible isolates, 49 strains (66.2%) exhibited heteroresistant phenotypes. All of the PMB-susceptible isolates showed heteroresistant phenotypes. Forty-six isolates (48.4%) were heteroresistant to both TGC and PMB. All of the isolates carried the blaKPC gene, and one strain carried both blaKPC and blaNDM genes. The time-kill assay revealed in four isolates that early bactericidal activity could be triggered by the combination of PMB and TGC, and there was no regrowth, even at a relatively lower concentration (0.125 mg/liter PMB with 1 mg/liter TGC). Upregulated expression of pmrA, phoP, and acrB indicated that heteroresistance could be related to two-component systems and the AcrAB-TolC efflux pump. The combination of PMB and TGC may be a treatment strategy for those infected with CRKP heteroresistant to PMB and/or TGC. IMPORTANCE Tigecycline and colistin are two of the last treatment options remaining for carbapenem-resistant Enterobacteriaceae. Unfortunately, tigecycline resistance and colistin heteroresistance are also increasing rapidly. In the current study, we identified a high prevalence of heteroresistance to both PMB and TGC among clinical isolates of carbapenem-resistant K. pneumoniae (CRKP). The resistant subpopulations could survive pressure from TGC or PMB but were killed by the combination at a relatively low dose. It is proposed that the combination of PMB and TGC may be a treatment strategy for patients who are infected with CRKP heteroresistant to PMB or TGC.

Characterization of Tigecycline-Heteroresistant Klebsiella pneumoniae Clinical Isolates From a Chinese Tertiary Care Teaching Hospital.

Tigecycline has been used as one of the therapeutic choices for the treatment of infections caused by multidrug-resistant Klebsiella pneumoniae. However, the emergence of tigecycline heteroresistance has led to great challenges in treating these infections. The purpose of this study was to investigate whether tigecycline-heteroresistant K. pneumoniae (TGCHR-Kp) exists in clinical isolates, and to further characterize the underlying molecular mechanisms involved in the development of tigecycline-resistant subpopulations. Of the 268 tigecycline-susceptible clinical K. pneumoniae isolates, 69 isolates were selected as tigecycline-heteroresistant candidates in the preliminary heteroresistant phenotypic selection by a modified disk diffusion method, and only 21 strains were confirmed as TGCHR-Kp by the population analysis profile (PAP). Pulsed-field gel electrophoresis (PFGE) analysis demonstrated that all the parental TGCHR-Kp isolates were clonally unrelated, and colonies confirmed as the heteroresistant subpopulation showed no significant differences from their respective parental TGCHR-Kp isolates. Efflux pump inhibitors reversed the tigecycline susceptibility in heteroresistant subpopulations. Mutations in the ramR and soxR genes lead to upregulation of the ramA and soxS transcriptional regulators, which in turn induced overexpression of the AcrAB-TolC efflux pump genes in TGCHR-Kps-resistant subpopulations. Moreover, mutations of rpsJ were also found in resistant subpopulations, which suggested that the rpsJ mutation may also lead to tigecycline resistance. Time-kill assays showed that the efficacy of tigecycline against TGCHR-Kps was weakened, whereas the number of resistant subpopulations was enriched by the presence of tigecycline. Our findings imply that the presence of TGCHR-Kps in clinical strains causes severe challenges for tigecycline therapy in clinical practice.

Helicobacter pylori outer inflammatory protein DNA vaccine-loaded bacterial ghost enhances immune protective efficacy in C57BL/6 mice.

Helicobacter pylori (H. pylori) infection is associated with incidents of gastrointestinal diseases in half of the human population. However, management of its infection remains a challenge. Hence, it is necessary to develop an efficient vaccine to fight against this pathogen. In the present study, a novel vaccine based on the production of attenuated Salmonella typhimurium bacterial ghost (SL7207-BG), delivering H. pylori outer inflammatory protein gene (oipA) encoded DNA vaccine was developed, and the efficiency was evaluated in C57BL/6 mice. Significant higher levels of IgG2a/IgG1 antibodies and IFN-γ/IL-4 cytokines were detected after mice were oral administered with oipA DNA vaccine loaded SL7207-BG, indicating that a mixed Th1/Th2 immune response was elicited. When challenged with infective doses H. pylori strain SS1, the ghost based vaccine was capable of reducing bacterium colonization in the vaccinated mice. In addition, codon-optimized oipA plasmid loaded SL7207-BG significantly eliminates H. pylori colonization density in mice model. Thus, it has been demonstrated that this novel bacterial ghost based DNA vaccine could be used as a promising vaccine candidate for the control of H. pylori infection.

Proliferative and apoptotic effects of gastric epithelial cells induced by coccoid Helicobacter pylori.

Helicobacter pylori exhibit morphology convertion in a spiral or coccoid form. This study aims to reveal the impact of coccoid H. pylori on the proliferation and apoptosis of gastric epithelial cells. The cagA and vacA genes of H. pylori were detected by semi-quantitative RT-PCR. Proliferation and apoptosis were analyzed by the CCK-8 colorimetric method and TUNEL assay, respectively. Egr-1 mRNA and PCNA expression affected by the ERK1/2-specific inhibitor were detected by RT-PCR and immunochemistry. At low density of infection (MOI < 125:1), coccoid H. pylori exerted a stronger effect on proliferation and a weaker effect on apoptosis than did spiral form. The ERK1/2-specific inhibitor significantly blocked the increased expression in Egr-1 and PCNA induced by coccoid H. pylori. Expression of vacA and cagA in coccoid H. pylori decreased compared with the spiral form, whereas vacA decreased more than cagA. The difference of proliferation and apoptosis may be related to the unequal decreased expression of vacA and cagA in coccoid H. pylori. Activation of the ERK1/2-Egr-1-PCNA signal transduction pathway may play an important role in coccoid H. pylori-induced cell proliferation. Long latency of the coccoid form of H. pylori in gastric tissue may be associated with gastric cancer caused by H. pylori.

Therapeutic vaccination with Salmonella-delivered codon-optimized outer inflammatory protein DNA vaccine enhances protection in Helicobacter pylori infected mice.

Vaccination had demonstrated as an alternative way to combat Helicobacter pylori challenge. In the present study, codon-optimized outer inflammatory protein gene (oipA) for Mus species codon usage, the inclusion of optimal Kozak sequence, and modified of GC content was applied to construct a novel DNA construct. The Salmonella-delivered wild type oipA construct (SL7207/poipA) and the Salmonella-delivered codon-optimized oipA construct (SL7207/poipA-opt) were prepared and their therapeutic efficacy was evaluated in H. pylori-infected mice. The codon-optimized oipA construct (poipA-opt) expressed almost six-fold higher protein than that of wild type construct (poipA) as normalized to the ß-actin expression in AGS cells. Oral therapeutic immunization with SL7207/poipA-opt significantly eliminated H. pylori colonization in the stomach; and protection was related to a robust Th1/Th2 immune response. Therefore, our results suggested that fine therapeutic efficacy was related to sufficient expression of the antigen. It is supposed that codon-optimized oipA gene improves protein expression and consequently enhances the immunogenicity of DNA vaccine, which resulted in a significant reduction of bacterial loads in H. pylori infected mice. The Salmonella-delivered codon-optimized DNA construct could be a candidate vaccine against H. pylori for the clinical application.

Enhancement of Helicobacter pylori outer inflammatory protein DNA vaccine efficacy by co-delivery of interleukin-2 and B subunit heat-labile toxin gene encoded plasmids.

Development of an effective vaccine for controlling H. pylori-associated infection, which is present in about half the people in the world, is a priority. The H. pylori outer inflammatory protein (oipA) has been demonstrated to be a potential antigen for a vaccine. In the present study, use of oipA gene encoded construct (poipA) for C57BL/6 mice vaccination was investigated. Whether co-delivery of IL-2 gene encoded construct (pIL-2) and B subunit heat-labile toxin of Escherichia coli gene encoded construct (pLTB) can modulate the immune response and enhance DNA vaccine efficacy was also explored. Our results demonstrated that poipA administered intradermally ('gene gun' immunization) promoted a strong Th2 immune response, whereas co-delivery of either pIL-2 or pLTB adjuvant elicited a Th1-biased immune response. PoipA administered with both pIL-2 and pLTB adjuvants promoted a strong Th1 immune response. Regardless of the different immune responses promoted by the various vaccination regimes, all immunized mice had smaller bacterial loads after H. pylori challenge than did PBS negative and pVAX1 mock controls. Co-delivery of adjuvant(s) enhances poipA DNA vaccine efficacy by shifting the immune response from being Th2 to being Th1-biased, which results in a greater reduction in bacterial load after H. pylori challenge. Both prophylactic and therapeutic vaccination can achieve sterile immunity in some subjects.