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This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 ± 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.

In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3–25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.

Burkholderia pseudomallei is a zoonotic pathogen that usually affects patients' lungs and causes serious melioidosis. The interaction of B. pseudomallei with its hosts is complex, and cellular response to B. pseudomallei infection in humans still remains to be elucidated. In this study, transcriptomic profiling of B. pseudomallei-infected human lung epithelial A549 cells was performed to characterize the cellular response dynamics during the early infection (EI) stage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the online databases DAVID 6.8 and KOBAS 3.0. Real-time quantitative PCR and western blot were used for validation experiments. Compared with the negative control group (NC), a set of 36 common genes varied over time with a cut-off level of 1.5-fold change, and a P-value < 0.05 was identified. Bioinformatics analysis indicated that the PERK-mediated unfolded protein response (UPR) was enriched as the most noteworthy biological process category, which was enriched as a branch of UPR in the signaling pathway of protein processing in the endoplasmic reticulum. Other categories, such as inflammatory responses, cell migration, and apoptosis, were also focused. The molecular chaperone Bip (GRP78), PERK, and PERK sensor-dependent phosphorylation of eIF2α (p-eIF2α) and ATF4 were verified to be increasing over time during the EI stage, suggesting that B. pseudomallei infection activated the PERK-mediated UPR in A549 cells. Collectively, these results provide important initial insights into the intimate interaction between B. pseudomallei and lung epithelial cells, which can be further explored toward the elucidation of the cellular mechanisms of B. pseudomallei infections in humans.

COVID -19 has rapidly spread from Wuhan to worldwide, and now has become a global health concern. Hypertension is the most common chronic illness in COVID-19, while the influence on those patients have not been well described. In this retrospective study, 82 confirmed patients with COVID-19 were enrolled, with epidemiological, demographic, clinical, laboratory, radiological, and therapies data analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. Of all 82 patients with COVID-19, the median age of all patients was 60.5 years, including 49 females (59.8%) and 33 (40.2%) males. Hypertension (31[28.2%]) was the most chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). Common symptoms included fatigue (55[67.1%]), dry cough (46 [56.1%]) and fever (≥37.3℃ (46 [56.1%]). The median time from illness onset to positive outcomes of RT-PCR analysis were 13.0 days, ranging from 3-25 days. In hypertension group, 6 (20.7%) patients died compared to 5 (9.4%) died in non-hypertension group. More hypertension patients with COVID-19 (8 [27.6%]) had at least one coexisting disease than those of non-hypertension patients (2 [3.8%]) (P=0.002). Compared with non-hypertension patients, higher levels of neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP were observed in hypertension group, whereas levels of lymphocyte count and eGFR were decreased. Dynamic observations displayed more significant and worsened outcomes in hypertension group after hospital admission. COVID-19 patients with hypertension take more risks of severe inflammatory reactions, worsened internal organ injuries, and deteriorated progress.

Background: Burkholderia pseudomallei causes melioidosis and usually affects patients’ lungs, its persistent infection promotes the fusion of host cells, leading to the formation of multinucleated giant cells (MGCs) at the late infected stage. In this study, the global transcriptomic responses of B. pseudomallei infection of a human lung epithelial A549 cell model with different infected stages were investigated by means of microarray analysis to further elucidate the host cellular factors involved in the occurrence and development of the event. Results: A set of 35 common differential expression genes (DEGs) in EI and LI on the mRNA level applying a cut-off level of 1.5-fold change and a p-value < 0.05 were observed. Microarray data were further verified by Real-Time quantitative PCR (RT-qPCR). GO classification and pathway enrichment analysis revealed these DEGs mainly involved in inflammatory response related processes, such as cellular response to tumor necrosis factor, cellular response to lipopolysaccharide, positive regulation of NF-κB transcription factor activity. p-eIF2α, ATF4,NF-κB2(p52) and IL-1β were next selected to be validated by western bloting, which indicated B. pseudomallei could activate the eIF2α-ATF4 axis and NF-κB2 pathway in A549 cells. Conclusion: Our data shed light on the transcriptome dynamics of A549 cells which persistently infected with B. pseudomallei and suggested that the formation of MGCs may be a means for B. pseudomallei to manipulate the host's inflammation and stress response to adapt to intracellular life.

Pseudomonas aeruginosa (PA) is the major causative agent of nosocomial infection. Despite of adequate use of antibiotics, it still represents a major challenge in controlling PA infection. The local pulmonary Th17 response plays an important protective role against PA infection. And the Th17-mediated protection is antibody independent, so we hypothesized that it would be an optimal strategy of a vaccine for PA control to induce an effective Th17 response. Herein we report the successful production of a recombinant fragment of the OprL (reOprL) of PA. Purified reOprL forms homogeneous monomers in solution and vaccination with reOprL elicited a remarkable Th17 response. In addition, reOprL vaccination conferred effective serotype-independent protection against PA infection, which relied on the Th17 response. Our data suggest that reOprL is a good candidate for the future development of Th17 immunity based PA vaccines.

Escherichia coli (E. coli) K1 causes meningitis and remains an unsolved problem in neonates, despite the application of antibiotics and supportive care. The cross-reactivity of bacterial capsular polysaccharides with human antigens hinders their application as vaccine candidates. Thus, protein antigens could be an alternative strategy for the development of an E. coli K1 vaccine. Outer membrane protein A (OmpA) of E. coli K1 is a potential vaccine candidate because of its predominant contribution to bacterial pathogenesis and sub-cellular localization. However, little progress has been made regarding the use of OmpA for this purpose due to difficulties in OmpA production. In the present study, we first investigated the immunogenicity of the four extracellular loops of OmpA. Using the structure of OmpA, we rationally designed and successfully generated the artificial protein OmpAVac, composed of connected loops from OmpA. Recombinant OmpAVac was successfully produced in E. coli BL21 and behaved as a soluble homogenous monomer in the aqueous phase. Vaccination with OmpAVac induced Th1, Th2, and Th17 immune responses and conferred effective protection in mice. In addition, OmpAVac-specific antibodies were able to mediate opsonophagocytosis and inhibit bacterial invasion, thereby conferring prophylactic protection in E. coli K1-challenged adult mice and neonatal mice. These results suggest that OmpAVac could be a good vaccine candidate for the control of E. coli K1 infection and provide an additional example of structure-based vaccine design.

SummaryBackgroundColonization of individual hosts by multiple Helicobacter pylori genotypes may be one reason why this infection is persistent and difficult to eradicate.MethodsIn order to study the diversity of H. pylori in individuals, a modified randomly amplified polymorphic DNA (RAPD) method was applied using primary culture isolates instead of passaged cultures.ResultsThe results showed that variations in H. pylori were prevalent among individuals in the Chinese population, and the incidence of multiple colonization was 99.1% (115/116), significantly higher than in other reports. Moreover, the number of RAPD genotypes was found to be significantly associated with the process of disease development (p

The human gastric pathogen, Helicobacter pylori, has co-evolved with its host and established itself in the human stomach possibly millions of years ago. Therefore, the diversity of this bacterium is important in its clinical manifestations. Our aim has been to evaluate the genetic diversity of 40 H. pylori clinical isolates from four different parts of China. The methods of multi-locus sequence typing and vacA allele genotyping were used to assess their genetic diversity. To discriminate MLST, the vacA genotype method was used to identify strains. Patients from the northern, eastern, southern, and southwestern parts of China were recruited randomly from the cities of Beijing, Shanghai, Guangzhou, and Chongqing, respectively. Most of the sequence types are new and have never been reported in the database of the H. pylori multi-locus sequence typing system. The most prevalent vacA genotype in patients was s1a/m2 (80.0%), followed by s1b/m2 (17.5%). In contrast, the s1a/m1 genotype was scarcely represented (2.5%). The vacA genotype varied for each ST. These results showed that the MLST method offers high resolution of the H. pylori isolates in China when compared to vacA genotyping. The vacA allelic s1a has been correlated with the peptic ulcer. Because of the paucity of data on human isolates due to the absence of systematic investigations of H. pylori in China, the data provide useful information for understanding the epidemiology of H. pylori in China from the viewpoint of nucleotide sequence databases.

Background H. pylori (Helicobacter pylori) is the major causative agent of chronic active gastritis. The population of H. pylori shows a high genomic variability among isolates. And the polymorphism of repeat-units of genomics had participated the important process of evolution. Its long term colonization of the stomach caused different clinical outcomes, which may relate to the high degree of genetic variation of H. pylori. A variety of molecular typing tools have been developed to access genetic relatedness in H. pylori isolates. However, there is still no standard genotyping system of this bacterium. The MLVA (Multi-locus of variable number of tandem repeat analysis) method is useful for performing phylogenetic analysis and is widely used in bacteria genotyping; however, there's little application in H. pylori analysis. This article is the first application of the MLVA method to investigate H. pylori from different districts and ethnic groups of China. Results MLVA of 12 VNTR loci with high discrimination power based on 30 candidates were performed on a collection of 202 strains of H. pylori which originated from five regions of China and Japan. Phylogenetic tree was constructed using MLVA profiles. 12 VNTR loci presented with high various polymorphisms, and the results demonstrated very close relationships between genotypes and ethnic groups. Conclusions This study used MLVA methodology providing a new perspective on the ethnic groups and distribution characteristics of H. pylori.