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Abstract Objective Dysphagia is common in individuals who have undergone posterior fossa tumor (PFT) resection and negatively impacts on the individual’s quality of life, nutritional status, and overall health. We aimed to quantitatively synthesize data from studies of the prevalence of dysphagia following PFT resection. Methods PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cross-sectional studies that evaluated the prevalence of dysphagia after PFT surgery. Meta-analyses were performed to determine the prevalence of dysphagia. Subgroup and meta-regression analyses were performed to determine the sources of heterogeneity among the studies. Results A total of 22 studies were included, involving 20,921 cases. A meta-analysis of the random-effects model showed that the pooled global prevalence of dysphagia following PFT resection was 21.7% (95% confidence interval: 16.9–26.6). The subgroup and meta-regression analyses demonstrated that participant age (P < 0.001), assessment methods (P = 0.004), and geographical region of the study participants (P = 0.001) were sources of heterogeneity among the studies. Conclusions Dysphagia has a high prevalence following PFT resection. Individuals with PFTs who are at a high risk for dysphagia should be identified early through screening. Multidisciplinary diagnosis and treatment of dysphagia are required to improve the outcomes in the early stages after PFT resection.

Abstract Background Hemorrhage is a common complication of nephrostomy and percutaneous nephrolithotripsy, and it is caused by surgical factors. Here we report a rare case of hemorrhage caused by sepsis-related coagulation dysfunction. Case presentation A 72-years-old male patient with bilateral ureteral calculi accompanied by hydronephrosis and renal insufficiency developed sepsis and hemorrhage on the third day after bilateral nephrostomy. After vascular injury was excluded by DSA, the hemorrhage was considered to be sepsis-associated coagulopathy(SAC/SIC), finally the patient recovered well after active symptomatic treatment. Conclusions In patients with sepsis and hemorrhage, SAC/SIC cannot be excluded even if coagulation function is slightly abnormal after surgical factors are excluded. For urologists who may encounter similar cases in their general urology practice, it is important to be aware of these unusual causes of hemorrhage.

Abstract Exosomes, membrane vesicles released extracellularly from cells, contain nucleic acids, proteins, lipids and other components, allowing the transfer of material information between cells. Recent studies reported the role of exosomes in pathogenic microbial infection and host immune mechanisms. Brucella‐invasive bodies can survive in host cells for a long time and cause chronic infection, which causes tissue damage. Whether exosomes are involved in host anti‐Brucella congenital immune responses has not been reported. Here, we extracted and identified exosomes secreted by Brucella melitensis M5 (Exo‐M5)‐infected macrophages, and performed in vivo and in vitro studies to examine the effects of exosomes carrying antigen on the polarization of macrophages and immune activation. Exo‐M5 promoted the polarization of M1 macrophages, which induced the significant secretion of M1 cytokines (tumour necrosis factor‐α and interferon‐γ) through NF‐κB signalling pathways and inhibited the secretion of M2 cytokines (IL‐10), thereby inhibiting the intracellular survival of Brucella. Exo‐M5 activated innate immunity and promoted the release of IgG2a antibodies that protected mice from Brucella infection and reduced the parasitaemia of Brucella in the spleen. Furthermore, Exo‐M5 contained Brucella antigen components, including Omp31 and OmpA. These results demonstrated that exosomes have an important role in immune responses against Brucella, which might help elucidate the mechanisms of host immunity against Brucella infection and aid the search for Brucella biomarkers and the development of new vaccine candidates.

Objective(s): Existing Brucella vaccines are attenuated and can cause vaccine-associated brucellosis; and these safety concerns have affected their application. Although subunit vaccines have the advantages of safety, efficacy, low cost, and rapid production, they are usually poorly immunogenic and insufficient to trigger persistent immunity. Therefore, we added layered double hydroxide (LDH) as an adjuvant to Brucella subunit vaccine formulations to enhance the immune response to the antigen.Materials and Methods: LDH and Freund’s adjuvant were combined with Brucella outer-membrane vesicles (OMVs) and OMV-associated proteins to form a subunit vaccine, respectively. The immunogenicity of LDH as an adjuvant was assessed in BALB/c mice. We examined levels of immunoglobulin G, G1, and G2a (IgG, IgG1, and IgG2a) antibodies (aBs); percentages of Cluster of Differentiation 4-positive (CD4+) and CD8+ T cells in peripheral-blood lymphocytes; and secretion of cytokines in mouse spleen lymphocytes. Finally, splenic index and splenic bacterial load were assessed via Brucella challenge experiments on mice.Results: The LDH subunit vaccine also produced high levels of specific aBs in mice compared with Freund’s adjuvant subunit vaccine and induced mainly T-helper 1 cell (Th1)-type immune responses. In addition, mice in the LDH subunit vaccine group had significantly lower bacterial loads in their spleens than those in the Freund’s adjuvant subunit vaccine group, and the LDH-OMV vaccine offered a higher level of protection against Brucella attack.Conclusion: LDH as an adjuvant-paired vaccine provided a high level of protection against Brucella infection.

IntroductionBrucella, a type of intracellular Gram-negative bacterium, has unique features and acts as a zoonotic pathogen. It can lead to abortion and infertility in animals. Eliminating brucellosis becomes very challenging once it spreads among both humans and animals, putting a heavy burden on livestock and people worldwide. Given the increasing spread of brucellosis, it is crucial to develop improved vaccines for susceptible animals to reduce the disease’s impact.MethodsIn this study, we effectively used an immunoinformatics approach with advanced computer software to carefully identify and analyze important antigenic parts of Brucella abortus. Subsequently, we skillfully designed chimeric peptides to enhance the vaccine’s strength and effectiveness. We used computer programs to find four important parts of the Brucella bacteria that our immune system recognizes. Then, we carefully looked for eight parts that are recognized by a type of white blood cell called cytotoxic T cells, six parts recognized by T helper cells, and four parts recognized by B cells. We connected these parts together using a special link, creating a strong new vaccine. To make the vaccine even better, we added some extra parts called molecular adjuvants. These included something called human β-defensins 3 (hBD-3) that we found in a database, and another part that helps the immune system called PADRE. We attached these extra parts to the beginning of the vaccine. In a new and clever way, we made the vaccine even stronger by attaching a part from a mouse’s immune system to the end of it. This created a new kind of vaccine called MEV-Fc. We used advanced computer methods to study how well the MEV-Fc vaccine interacts with certain receptors in the body (TLR-2 and TLR-4).ResultsIn the end, Immunosimulation predictions showed that the MEV-Fc vaccine can make the immune system respond strongly, both in terms of cells and antibodies.DiscussionIn summary, our results provide novel insights for the development of Brucella vaccines. Although further laboratory experiments are required to assess its protective effect.

Traditional Chinese medicine (TCM) formulas can be adjusted on the basis of TCM basic theory to achieve the best curative effect, especially for diseases with complex pathogenesis, such as post-weaning diarrhea (PWD). Shugan Jianwei Sijunzi decoction (SJ-SJZD) can be recognized as modified Sijunzi Decoction (SJZD) supplemented with Astragalus mongholicus Bunge, Bupleurum chinense DC, Citrus × aurantium L., and Crataegus pinnatifida Bunge (fruit) in a fixed dosage ratio. The inactive ingredients were subsequently added to make granule, which was Shugan Jianwei Sijunzi granule (SJ-SJZG). Previous studies have confirmed the antagonism of SJ-SJZG to PWD. However, the mechanism of SJ-SJZG protective effects on small intestine in weaned Rex rabbits remained unclear. Animals were randomly divided into negative control (NC), low dose (LD), medium dose (MD), high dose (HD), and positive control (PC). SJ-SJZG significantly increased the intestinal length and the jejunum villi length. The SIgA level was statistically increased in duodenum and jejunum with the ELISA. Immunohistochemical detection showed that SIgA protein expression was also increased significantly in jejunum. Meanwhile, the relative expression of Zo1 in duodenum and jejunum of SJ-SJZG group increased significantly. SJ-SJZG significantly increased the relative expression of occludin in duodenum and jejunum as well. Moreover, real-time PCR results showed a significant increase in GLUT2 and SGLT1 relative expression in ileum. SJ-SJZG could also obviously enhance the expression of GLUT2 in jejunum and the expression of SGLT1 in duodenum. In conclusion, SJ-SJZG had been proven to be effective in promoting the development of small intestine and improving the immunity of small intestine. Moreover, SJ-SJZG could ensure the integrity of mucosal barrier and increase the ability of intestine to absorb glucose in small intestine.

BackgroundTissue inhibitor of metalloproteinase-1 (TIMP-1) levels is strongly associated with cardiac extracellular matrix accumulation and atrial fibrosis. Whether serum levels of TIMP-1 are associated with atrial fibrillation (AF) recurrence following radiofrequency catheter ablation (RFCA) remains unknown.Materials and methodsSerum TIMP-1 levels of patients with AF before they underwent initial RFCA were measured using ELISA. Univariate and multivariate-adjusted Cox models were constructed to determine the relationship between TIMP-1 levels and AF recurrence. Multivariate logistic regression analyses were performed to determine predictors of AF recurrence.ResultsOf the 194 enrolled patients, 61 (31.4%) had AF recurrence within the median 30.0 months (interquartile range: 16.5–33.7 months) of follow-up. These patients had significantly higher baseline TIMP-1 levels than those without AF recurrence (129.8 ± 65.7 vs. 112.0 ± 51.0 ng/ml, P = 0.041). The same was true of high-sensitivity C-reactive protein (3.9 ± 6.0 vs. 1.9 ± 2.8 ng/ml, P = 0.001). When a TIMP-1 cutoff of 124.15 ng/ml was set, patients with TIMP-1 ≥ 124.15 ng/ml had a higher risk of recurrent AF than those with TIMP-1 < 124.15 ng/ml (HR, 1.961, 95% CI, 1.182–2. 253, P = 0.009). Multivariate Cox regression analysis revealed that high TIMP-1 was an independent risk factor for AF recurrence. Univariate Cox regression analysis found that substrate modification surgery does not affect AF recurrence (P = 0.553). Subgroup analysis revealed that female sex, age < 65 years, hypertension (HTN), body mass index (BMI) ≥ 24 kg/m2, CHA2DS2-VASc score < 2, HAS-BLED score < 3, and EHRA score = 3 combined with high TIMP-1 level would perform well at predicting AF recurrence after RFCA.ConclusionElevated preoperative TIMP-1 levels are related to a higher risk of AF recurrence and can independently predict AF recurrence following RFCA.

Brucellosis, caused by Brucella spp., is one of the most widespread bacterial zoonoses worldwide. Vaccination is still considered the best way to control brucellosis. An investigation into the differential proteome expression patterns of wild and vaccine strains may help researchers and clinicians differentiate between the strains to diagnose and better understand the mechanism(s) underlying differences in virulence. In the present study, a mass spectrometry-based, label-free relative quantitative proteomics approach was used to investigate the proteins expressed by the wild strain, B. melitensis biovar 3 and compare it with those expressed by B. melitensis M5-90. The higher level of virulence for B. melitensis biovar 3 compared to B. melitensis M5-90 was validated in vitro and in vivo. A total of 2133 proteins, encompassing 68% of the theoretical proteome, were identified and quantified by proteomic analysis, resulting in broad coverage of the B. melitensis proteome. A total of 147 proteins were identified as differentially expressed (DE) between these two strains. In addition, 9 proteins and 30 proteins were identified as unique to B. melitensis M5-90 and B. melitensis biovar 3, respectively. Pathway analysis revealed that the majority of the DE proteins were involved in iron uptake, quorum sensing, pyrimidine metabolism, glycine betaine biosynthetic and metabolic processes, thiamine-containing compound metabolism and ABC transporters. The expression of BtpA and VjbR proteins (two well-known virulence factors) in B. melitensis biovar 3 was 8-fold and 2-fold higher than in B. melitensis M5-90. In summary, our results identified many unique proteins that could be selected as candidate markers for differentiating vaccinated animals from animals with wild-type infections. BtpA and VjbR proteins might be responsible for the residual virulence of B. melitensis M5-90, while ABC transporters and thiamine metabolism associated proteins may be newly identified Brucella virulence factors. All of the identified DE proteins provide valuable information for the development of vaccines and the discovery of novel therapeutic targets.

Abstract Background This case report describes the clinical process of a shepherd who suffered brucellosis-related endocarditis (BE) and spondylitis (BS) and was infected with Brucella melitensis biovar 3 (B. melitensis biovar 3). Case presentation A 55-year-old male patient was admitted to The First Affiliated Hospital of Shihezi University on October 11, 2018, due to over 3 months of intermittent fever, back pain, and heart trouble. The Rose Bengal Plate test was positive, the standard agglutination test titer for brucellosis was 1/800, and the blood culture was positive for B. melitensis biovar 3. Three instances of transthoracic echocardiography examination at days 1, 25, and 376 after admission to the hospital and magnetic resonance imaging (MRI) and computed tomography (CT) checks at days 5 and 38 revealed that the size of the vegetation on the posterior leaflet of the mitral valve increased from 0.7 × 1.4 cm to 1.2 × 1.5 cm and that the left atrium and ventricle were enlarged. The MRI and CT results showed hyperplasia of the second and third vertebra, a cold abscess formed on both sides of the psoas major muscles, and the vertebra hyperplasia became aggravated at a later time point. The patient’s situation deteriorated, and heart failure was discovered on October 22, 2019. At the moment of submission of this manuscript, the patient remains in bed at home because of severe debility caused by brucellosis. Conclusions This is the first reported case of endocarditis combined with spondylitis caused by B. melitensis biovar 3 in a shepherd. Brucellosis infection can cause work-power losses because of misdiagnosis or a lack of proper treatment. Early diagnosis and treatment are essential for a successful outcome.

The aim of this study is to investigate the role of outer membrane protein Omp19 of Brucella in its pathogenesis. In this research, the Brucella 2308 ΔOmp19 deletion mutant was constructed and its intracellular survivability was evaluated in murine macrophages RAW264.7 and BALB/c mice. We also analyzed the lysosomal fusion induced by and cytotoxicity of Brucella in murine macrophages RAW264.7. The results showed that the Brucella 2308 ΔOmp19 induced higher levels of immunoprotective cytokines in vitro than Brucella 2308, and the number of intracellular bacteria in RAW264.7 macrophages was lower after Brucella 2308 ΔOmp19 infection than after Brucella 2308 infection. In vivo, Brucella 2308 ΔOmp19 induced protective immune response in mice, and the splenic bacterial load of this deletion mutant was lower than that of Brucella 2308. In addition, the Brucella 2308 ΔOmp19 also promoted the fusion of Brucella-containing vacuoles and lysosomes, in macrophages. Therefore, Brucella 2308 ΔOmp19 reduced virulence compared with Brucella 2308 and activate the immune response of the host, and is a promising candidate for a live attenuated vaccine.

Thoracic aortic aneurysm and dissection (TAAD) is a high-risk aortic disease. Mouse models are usually used to explore the pathological progression of TAAD. In our studies, we performed bioinformatics analysis on a microarray dataset (GSE36778) and verified experiments to define the integrated hub genes of TAAD in three different mouse models. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network analyses, and histological and quantitative reverse transcription-PCR (qRT–PCR) experiments were used in our study. First, differentially expressed genes (DEGs) were identified, and twelve common differentially expressed genes were found. Second, genes related to the cell cycle and inflammation were enriched by using GO and PPI. We focused on filtering and validating eighteen hub genes that were upregulated. Then, expression data from human ascending aortic tissues in the GSE153434 dataset were also used to verify our findings. These results indicated that cell cycle-related genes participate in the pathological mechanism of TAAD and provide new insight into the molecular mechanisms of TAAD.

Abstract: The Shone’s complex, defined as a constellation of parachute mitral valve (PMV), supravalvular ring of the left atrium, subaortic stenosis, and aorta coarctation, is a rare entity, which more commonly occurs in its incomplete form. We report the case of a 28-year-old female patient who presented for chest congestion and palpitation with history of congenital mitral valve malformation. Echocardiography revealed the coexistence of PMV, aortic coarctation with bicuspid aortic valve (BAV), and ventricular septum defect (VSD). The patient then received surgical intervention. The diagnosis of Shone’s complex with BAV and VSD made by echocardiography were confirmed later at surgery.

Aims: To determine the agreement between two-dimensional transthoracic echocardiography (2DTTE) and cardiovascular magnetic resonance (CMR) in left ventricular (LV) function [including end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF)] in chronic total occlusion (CTO) patients.Methods: Eighty-eight CTO patients were enrolled in this study. All patients underwent 2DTTE and CMR within 1 week. The correlation and agreement of LVEF, LVESV, and LVEDV as measured by 2DTTE and CMR were assessed using Pearson correlation, Kappa analysis, and Bland–Altman method.Results: The mean age of patients enrolled was 57 ± 10 years. There was a strong correlation (r = 0.71, 0.90, and 0.80, respectively, all P < 0.001) and a moderately strong agreement (Kappa = 0.62, P < 0.001) between the two modalities in measurement of LV function. The agreement in patients with EF ≧50% was better than in those with an EF

Exosomes are small extracellular vesicles that are released from cells and that function in intercellular communication. Recently, interferon-inducible transmembrane protein 3 (IFITM3) has been identified as a highly effective anti-intracellular pathogen protein that can inhibit the invasion of a wide range of pathogenic microorganisms. However, whether Brucella infection induces secretion of exosomes and whether these exosomes contain IFITM3 protein remain unknown. Here, we focused on the immune function of extracellular IFITM3 protein in the process of Brucella infection. This study is the first to show that Brucella melitensis strain M5 (Brucella M5) can stimulate macrophages to secrete large amounts of exosomes. Most importantly, we identified exosomes from Brucella M5-infected cells that were rich in molecules of IFITM3, and these exosomes could transmit the IFITM3 from one cell to another, thereby effectively inhibiting the intracellular survival of Brucella. Moreover, immunization with exosomes carrying IFITM3 decreased mouse spleen tissue damage and spleen colony forming unit (CFU), leading to the establishment of an anti-Brucella state in mice. In conclusion, our findings provide new insights into the anti-Brucella mechanism of IFITM3-containg exosomes, thus providing a theoretical foundation for systematic elaboration of the mechanisms of Brucella infection and host immunity. The results provide new ideas for the development of candidate vaccines for Brucella.

Brucella is a genus of Gram-negative intracellular pathogens that cause animal and human diseases. Brucella survival and replication inside immune cells is critical for the establishment of chronic infections. Protein modifications by small ubiquitin-related modifier proteins and the NF-κB pathway are involved in many cellular activities, playing major roles in regulating protein function that is essential for pathogenic bacteria during infection. However, the relationship between them in the intracellular survival of Brucella is still largely unknown. We demonstrated that Brucella abortus 2308 infection can activate the expression of small ubiquitin-related modifier-2 proteins in a time-dependent manner. We found the production of Th1 cytokines (IFN-γ and TNF-α) and the transcription of NF-κB/p65 were promoted by overexpression and inhibited by interference of small ubiquitin-related modifier-2. In addition, we showed that small ubiquitin-related modifier-2 can inhibit intracellular survival of Brucella abortus 2308 by regulating activation of the NF-κB pathway. Taken together, this work shows that small ubiquitin-related modifier-2 modification of NF-κB2/p65 is essential for the survival of Brucella abortus 2308 inside macrophages. This work may help to unravel the pathogenic mechanisms of Brucella infections.

Brucellosis is serious zoonotic disease affecting both animals and humans. Brucella inhibits the apoptosis of host macrophages. And the JAK2/STAT3 pathway regulates various cellular physiological activities. However, the association between Brucella-mediated inhibition of macrophage apoptosis and regulation of the JAK2/STAT3 pathway is unclear. In the current study, We tested the the activation of JAK2/ STAT3 pathway and evaluated its function during Brucella M5-90 infection in cells. The result was found that infection with Brucella M5-90 activated the JAK2/STAT3 pathway and induced phosphorylation of both JAK2 and STAT3 in a time-dependent manner. JAK2 and STAT3 phosphorylation were inhibited by AG490 in a dose-dependent manner. Inhibition of the JAK2/STAT3 pathway with AG490 significantly induced proinflammatory responses, macrophage apoptosis at the transcriptional and protein levels, as well as intracellular survival and replication of Brucella M5-90. This study indicates that the JAK2/STAT3 pathway plays a major role in macrophage apoptosis induced by infection with Brucella M5-90. In addition, TNF-α plays a major role in the regulation of the JAK2/STAT6 pathway during Brucella M5-90 infection. The above information may help to unravel the pathogenic mechanism of Brucella infection.

Marfan syndrome (MFS) is an autosomal dominant genetic disorder of the connective tissue, typically characteristic of cardiovascular manifestations, valve prolapse, left ventricle enlargement, and cardiac failure. Fibrillin-1 (FBN1) is the causative gene in the pathogenesis of MFS. Patients with different FBN1 mutations often present more considerable phenotypic variation. In the present study, three affected MFS pedigrees were collected for genetic analysis. Using next-generation sequencing (NGS) technologies, 3 novel frameshift pathogenic mutations which are cosegregated with affected subjects in 3 pedigrees were identified. These novel mutations provide important diagnostic and therapeutic insights for precision medicine in MFS, especially regarding the lethal cardiovascular events.

Medial degeneration and inflammation are features of abdominal aortic aneurysms (AAAs). However, the early inflammatory event initiating aneurysm formation remains to be identified. Activated platelets release abundant proinflammatory cytokines and are involved in initial inflammation in various vascular diseases. We investigated the role of platelets in progression of AAA in vivo and in vitro. Histological studies of tissues of patients with AAA revealed that the number of platelets was increased in aneurysm sites along with the increased infiltration of T lymphocytes and augmented angiogenesis. In a murine model of AAA, apolipoprotein E-knockout mice infused with 1,000 ng/kg/min angiotensin II, treatment with clopidogrel, an inhibitor of platelets, significantly suppressed aneurysm formation (47% decrease, P