Methodological Validation and Inter-Laboratory Comparison of Microneutralization Assay for Detecting Anti-AAV9 Neutralizing Antibody in Human.

Anti-AAV neutralizing Abs (NAbs) titer is usually measured by cell-based microneutralization (MN) assay and is crucial for patient screening in AAV-based gene therapy clinical trials. However, achieving uniform operation and comparable results among different laboratories remains challenging. Here, we established a standardized MN assay for anti-AAV9 NAbs in human sera or plasma and transferred the method to the other two research teams. Then, we validated its parameters and tested a set of eight human samples in blind across all laboratories. The end-point titer, defined by a transduction inhibition of 50% (IC50), was calculated using curve-fit modelling. A mouse neutralizing monoclonal antibody in human negative serum was used for system quality control (QC), requiring inter-assay titer variation of <4-fold difference or geometric coefficient of variation (%GCV) of <50%. The assay demonstrated a sensitivity of 54 ng/mL and no cross-reactivity to 20 µg/mL anti-AAV8 MoAb. The intra-assay and inter-assay variation for the low positive QC were 7-35% and 22-41%, respectively. The titers of the blind samples showed excellent reproducibility within and among laboratories, with a %GCV of 18-59% and 23-46%, respectively. This study provides a commonly transferrable MN assay for evaluating anti-AAV9 NAbs in humans, supporting its application in clinical trials.

Metabolomic profiles and differential metabolites of volatile components in Citrus aurantium Changshan-huyou pericarp during different growth and development stages.

Citrus fruits possess a distinctive aroma and flavor, with Citrus aurantium Changshan-huyou (CACH) standing out due to their considerable edible and medicinal value. However, the volatile components (VOCs) in the CACH pericarp (CP) remain underexplored. In this study, gas chromatography-mass spectrometry (GC-MS) was utilized to qualitatively analyze VOCs in 27 CP samples across different growth stages. A total of 544 VOCs were identified, including 91 terpenoids. The types, quantities and distributions of VOCs were conducted. Detailed discussions on the major terpenoids in CP were also presented. A metabolomics approach combining multivariate statistical analysis with univariate analysis was employed for screening the differential metabolites. The study provides comprehensive insights into the VOCs in CP and citrus plants. Moreover, it delivers the first in-depth analysis of differential metabolites in CP throughout the entire CACH growth and development process, laying a foundation for ongoing research and development of the VOCs in CP.

Comparative transcriptomic analysis of hepatopancreas reveals that more genes are involved in the exposure response of Vibrio parahaemolyticus PirAvp compared to PirBvp.

Vibrio parahaemolyticus (VP-AHPND) is regarded as one of the main pathogens that caused acute hepatopancreatic necrosis disease (AHPND) in the Pacific white shrimp Litopenaeus vannamei. PirAvp and PirBvp toxin proteins are the main pathogenic proteins of AHPND in shrimp. Knowledge about the mechanism of shrimp response to PirAvp or PirBvp toxin is very helpful for developing new prevention and control strategy of AHPND in shrimp. In this study, the pathological sections showed that after 4 h treatment, significant pathological changes were observed in the PirBvp treated group, and no obvious pathological changes was found in PirAvp treated group. In order to learn the mechanism of shrimp response to PirAvp and PirBvp, comparative transcriptome was applied to analyze the different expressions of genes in the hepatopancreas of shrimp after treatment with PirAvp or PirBvp. A total of 9978 differentially expressed genes (DEGs) were identified between PirAvp or PirBvp-treated and PBS control shrimp, including 6616 DEGs in the PirAvp treated group and 3362 DEGs in the PirBvp treated group. There were 2263 DEGs that were commonly expressed, 4353 DEGs were only expressed in PirAvp VS PBS group and 1099 DEGs were uniquely expressed in PirBvp VS PBS group. Among these DEGs, the anti-apoptosis related pathways and immune response related genes significantly expressed in the commonly expressed DEGs of PirAvp VS PBS group and PirBvp VS PBS group, and small GTPase-mediated signaling and DNA metabolic process might relate to the host special reaction towards PirAvp and PirBvp exposure. The data suggested that the differential expression of these immune and metabolic-related genes in hepatopancreas might contribute to the pathogenicity variations of shrimp to VP-AHPND. The identified genes in this study will be useful for clarifying the response mechanism of shrimp toward different toxins of VP-AHPND and will further provide molecular basis for understanding the pathogenic mechanism of VP-AHPND.

In sight the behavior of natural Bletilla striata polysaccharide hydrocolloids by molecular dynamics method.

Plant polysaccharides, distinguished by diverse glycosidic bonds and various cyclic sugar units, constitute a subclass of primary metabolites ubiquitously found in nature. Contrary to common understanding, plant polysaccharides typically form hydrocolloids upon dissolution in water, even though both excessively high and low temperatures impede this process. Bletilla striata polysaccharides (BSP), chosen for this kinetic study due to their regular repeating units, help elucidate the relationship between polysaccharide gelation and temperature. It is suggested that elevated temperatures enhance the mobility of BSP molecular chains, resulting in a notable acceleration of hydrogen bond breakage between BSP and water molecules and consequently, compromising the conformational stability of BSPs to some extent. This study unveils the unique relationship between polysaccharide dissolution processes and temperature from a kinetics perspective. Consequently, the conclusion provides a dynamical basis for comprehending the extraction and preparation of natural plant polysaccharide hydrocolloids, pharmaceuticals and related fields.

Epithelium-derived kallistatin promotes CD4+ T-cell chemotaxis to TH2-type inflammation in chronic rhinosinusitis.

BACKGROUND: The function of kallistatin in airway inflammation, particularly chronic rhinosinusitis with nasal polyps (CRSwNP), has not been elucidated. OBJECTIVE: We sought to investigate the role of kallistatin in airway inflammation. METHODS: Kallistatin and proinflammatory cytokine expression levels were detected in nasal polyps. For the in vivo studies, we constructed the kallistatin-overexpressing transgenic mice to elucidate the role of kallistatin in airway inflammation. Furthermore, the levels of plasma IgE and proinflammatory cytokines in the airways were evaluated in the kallistatin-/- rat in vivo model under a type 2 inflammatory background. Finally, the Notch signaling pathway was explored to understand the role of kallistatin in CRSwNP. RESULTS: We showed that the expression of kallistatin was significantly higher in nasal polyps than in the normal nasal mucosa and correlated with IL-4 expression. We also discovered that the nasal mucosa of kallistatin-overexpressing transgenic mice expressed higher levels of IL-4 expression, associating to TH2-type inflammation. Interestingly, we observed lower IL-4 levels in the nasal mucosa and lower total plasma IgE of the kallistatin-/- group treated with house dust mite allergen compared with the wild-type house dust mite group. Finally, we observed a significant increase in the expression of Jagged2 in the nasal epithelium cells transduced with adenovirus-kallistatin. This heightened expression correlated with increased secretion of IL-4, attributed to the augmented population of CD4+CD45+Notch1+ T cells. These findings collectively may contribute to the induction of TH2-type inflammation. CONCLUSIONS: Kallistatin was demonstrated to be involved in the CRSwNP pathogenesis by enhancing the TH2 inflammation, which was found to be associated with more expression of IL-4, potentially facilitated through Jagged2-Notch1 signaling in CD4+ T cells.

The comparative analysis of Lonicerae Japonicae Flos and Lonicerae Flos: A systematical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) were once used as the same herb in China, but they were distinguished by Chinese Pharmacopoeia in 2005 in terms of their medicinal history, plant morphology, medicinal properties and chemical constituents. However, their functions, flavor, and meridian tropism are the same according to the Chinese pharmacopoeia 2020 edition, making researchers and customers confused. AIM OF THE REVIEW: This review aimed to provide a comparative analysis of LJF and LF in order to provide a rational application in future research. MATERIALS AND METHODS: The information was gathered from China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations (all chosen articles were reviewed attentively from 1980.1 to 2023.8). RESULTS: Till now, 507 chemical compounds have been isolated and identified in LJF, while 223 ones (79 overlapped compounds) are found in LF, including organic acids and derivatives, flavonoids, triterpenoids, iridoids, and essential oil components, etc. In addition, the pharmacological activities of LJF and LF, especially for their anti-influenza efficacy and mechanism, and their difference in terms of pharmacokinetic parameters, toxicology, and clinical applications were also summarized. CONCLUSION: The current work offers comparative information between LJF and LF in terms of botany, traditional uses, phytochemistry, ethnopharmacology, pharmacokinetics, toxicology, and pharmacology, especially their anti-influenza activities. Despite the same clinical applications and similar chemical components in LJF and LF, differentiated components were still existed, resulting in differentiated pharmacological activities and pharmacokinetics parameters. Moreover, the research about anti-influenza mechanism and functional substances of LJF and LF is dramatically limited, restricting their clinical applications. In addition, few studies have investigated the metabolism feature of LF in vivo, which is one of the important bases for revealing the pharmacological mechanism of LF. At the same time, the toxicity of LJF and LF is not fully studied, and the toxic compounds of LJF and LF need to be screened out in order to standardize the drug use and improve their rational applications.

A Zwitterionic Hydrogel with Anti-Oxidative and Anti-Inflammatory Properties for the Prevention of Peritoneal Adhesion by Inhibiting Mesothelial-Mesenchymal Transition.

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-ß). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.

Trends and disparities in China's cardiovascular disease burden from 1990 to 2019.

BACKGROUND AND AIMS: In order to find the exact strategies in the prevention of cardiovascular diseases (CVD), it is necessary to assess their risk factors systematically. Here, we used the Global Burden of Disease (GBD) to review the long-term trends and epidemiological characteristics among Chinese. METHODS AND RESULTS: We comprehensively analyzed the burden of CVD for the Chinese population using GBD 2019, including prevalence, incidence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). Then, we analyzed trends over time, and predicted mortality and morbidity, using joinpoint regression, age-period-cohort (APC) model, and Bayesian APC approach. Finally, we analyzed the attributable burden of CVD. In 2019, the prevalence of CVD in China was 120 million, representing a 140.02% increase since 1990. The number of DALYs attributed to CVD increased by 52.56% compared to 1990. Joinpoint showed a fluctuating incidence downward, while mortality significantly declined. The APC fitting results indicated that recent generations have a higher prevalence than the past, and the prevalence has increased among individuals of the same age group. The BAPC predicted that CVD's prevalence and mortality in the Chinese would stabilize and decline between 2020 and 2030, with a significant decline among males. The main CVD-attributable burdens in 2019 were metabolic risks, especially high blood pressure. CONCLUSION: Given China's large and rapidly aging population, the burden of CVD is a major concern. Practical strategies to prevent and manage CVD are urgently needed to address this public health challenge.

Preparation and Characterization of Porous Cellulose Acetate Nanofiber Hydrogels.

The currently reported methods for preparing cellulose acetate hydrogels use chemical reagents as cross-linking agents, and the prepared ones are non-porous structured cellulose acetate hydrogels. Nonporous cellulose acetate hydrogels limit the range of applications, such as limiting cell attachment and nutrient delivery in tissue engineering. This research creatively proposed a facile method to prepare cellulose acetate hydrogels with porous structures. Water was added to the cellulose acetate-acetone solution as an anti-solvent to induce the phase separation of the cellulose acetate-acetone solution to obtain a physical gel with a network structure, where the cellulose acetate molecules undergo re-arrangement during the replacement of acetone by water to obtain hydrogels. The SEM and BET test results showed that the hydrogels are relatively porous. The maximum pore size of the cellulose acetate hydrogel is 380 nm, and the specific surface area reaches 62 m2/g. The porosity of the hydrogel is significantly higher than that of the cellulose acetate hydrogel reported in the previous literature. The XRD results show that the nanofibrous morphology of cellulose acetate hydrogels is caused by the deacetylation reaction of cellulose acetate.

Zwitterionic Polysaccharide-Based Hydrogel Dressing as a Stem Cell Carrier to Accelerate Burn Wound Healing.

Stem cell therapy integrated with hydrogels has shown promising potential in wound healing. However, the existing hydrogels usually cannot reach the desired therapeutic efficacy for burn wounds due to the inadaptability to wound shape and weak anti-infection ability. Moreover, it is difficult to improve the environment for the survival and function of stem cells under complicated wound microenvironments. In this study, an injectable and self-healing hydrogel (DSC), comprising sulfobetaine-derived dextran and carboxymethyl chitosan, is fabricated through a Schiff-base reaction. Meanwhile, the DSC hydrogel shows high nonfouling properties, including resistance to bacteria and nonspecific proteins; moreover, the prepared hydrogel can provide a biomimetic microenvironment for cell proliferation whilst maintaining the stemness of adipose-derived stem cells (ADSCs) regardless of complex microenvironments. In burnt murine animal models, the ADSCs-laden hydrogel can significantly accelerate wound healing rate and scarless skin tissue regeneration through multiple pathways. Specifically, the ADSCs-laden DSC hydrogel can avoid immune system recognition and activation and thus reduce the inflammatory response. Moreover, the ADSCs-laden DSC hydrogel can promote collagen deposition, angiogenesis, and enhance macrophage M2 polarization in the wound area. In summary, sulfobetaine-derived polysaccharide hydrogel can serve as a versatile platform for stem cell delivery to promote burn wound healing.

Therapeutic potential of recombinant human basic fibroblast growth factor on postoperative patients with chronic rhinosinusitis with nasal polyps.

OBJECTIVES: To explore the effect of intranasal administration of recombinant human basic fibroblast growth factor (rh-bFGF) on postoperative chronic rhinosinusitis with nasal polyps (CRSwNP) patients. DESIGN: A prospective, randomised, controlled, single-blinded trial. SETTING AND PARTICIPANTS: Seventy-five hospitalised patients who met the criteria of primary bilateral CRSwNP were enrolled from March 2020 to January 2021. MAIN OUTCOME MEASURES: Visual analogue scale, 22-item Sino-Nasal Outcome Test, Lund-Kennedy (L-K) system and scanning electron microscopy and quantitative real-time polymerase chain reaction. RESULTS: Seventy-five patients with CRSwNP were randomly assigned to three groups, and 72 patients completed the 1-month medication regimen and 1-year follow-up. Rh-bFGF nasal-spray and drop application reduced general nasal VAS scores within 2 weeks after endoscopic sinus surgery (ESS) compared to the control group. In contrast, only rh-bFGF nasal-drops reduced SNOT-22 scores at 2 weeks and 1 year compared with the control group. A significant reduction in the endoscopic L-K score was observed in the rh-bFGF nasal-spray and drop group compared with the control group. This is primarily because rh-bFGF promotes cilia growth in the nasal mucosal epithelium after the operation, as illustrated by scanning electron microscopy and expression of CP110, Tap73 and Foxj1 mRNA. For eosinophilic CRSwNP, the general VAS score of rh-bFGF nasal-drops was more obviously reduced compared to the control group after ESS. A similar trend was observed for L-K score. CONCLUSIONS: Rh-bFGF nasal-drops and sprays can quickly and effectively relieve postoperative symptoms and improve long-term prognosis of patients with CRSwNP. Moreover, rh-bFGF nasal-drops is also an effective method for postoperative patients with eosinophilic CRSwNP.

Chlorination of L-tyrosine and metal complex: degradation kinetics and disinfection by-products generation.

The presence of metal ions in drinking water treatment and distribution systems may affect the disinfection process of organic matter, which had aroused people's concern. L-tyrosine can complex with metal ions through carboxyl, carbonyl, and amino groups and affect its chemical reactions. In this paper, the complexation of L-tyrosine with common metal ions was studied and the influence of complexation on chlorination with different experimental factors was investigated. It was inferred that L-tyrosine complexed with metal ions by single dentate ligand or double dentate chelation in a ratio of 2:1. The degradation of L-tyrosine-metal complex followed the pseudo-first-order reaction kinetic. TCM, DCAA, and TCAA were the main species DBPs in the chlorination of L-tyrosine. Compared with L-tyrosine, the reaction rate constants of complex increased by 5.6%, the formation of trihalomethane production decreased by 21.5% and the formation of haloacetic acids production increased by 26.9% at the state of metal complexation. The effect of metal complexation on chlorination was more obvious than that of metal coexistence. For different metal complexation, the order of inhibition on trihalomethane production was Ca2+> Fe3+> Mn2+ and the order of promotion on haloacetic acids production was Mn2+> Fe3+> Ca2+. Moreover, it was found that alkaline conditions were favorable for the formation of DBPs due to the hydroxyl radical. The combination of ultraviolet and chlorine disinfection promoted L-Tyrosine degradation and DBPs generation, and the promotion efficiency follow the order: UV/Cl2> UV-Cl2> Cl2.

An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.

Directed Brain Network Analysis for Fatigue Driving Based on EEG Source Signals.

Fatigue driving is one of the major factors that leads to traffic accidents. Long-term monotonous driving can easily cause a decrease in the driver's attention and vigilance, manifesting a fatigue effect. This paper proposes a means of revealing the effects of driving fatigue on the brain's information processing abilities, from the aspect of a directed brain network based on electroencephalogram (EEG) source signals. Based on current source density (CSD) data derived from EEG signals using source analysis, a directed brain network for fatigue driving was constructed by using a directed transfer function. As driving time increased, the average clustering coefficient as well as the average path length gradually increased; meanwhile, global efficiency gradually decreased for most rhythms, suggesting that deep driving fatigue enhances the brain's local information integration abilities while weakening its global abilities. Furthermore, causal flow analysis showed electrodes with significant differences between the awake state and the driving fatigue state, which were mainly distributed in several areas of the anterior and posterior regions, especially under the theta rhythm. It was also found that the ability of the anterior regions to receive information from the posterior regions became significantly worse in the driving fatigue state. These findings may provide a theoretical basis for revealing the underlying neural mechanisms of driving fatigue.

Does YouTube Provide Qualified Patient Education Videos About Atrial Fibrillation?

Objective: Patients utilize the internet as a pathway to acquire knowledge of specific diseases. However, there are limited oversight and review mechanisms to ensure the authenticity of online information. This study aimed to evaluate the quality of video-based resources used to obtain information about atrial fibrillation (AF). Methods: Multiple AF-specific keywords were used to perform a systematic search of YouTube. Two independent reviewers reviewed the top 50 results of each keyword search. To record data, the Journal of the American Medical Association (JAMA) score, modified DISCERN score, AF-specific score (AFSS), and essential score (Escore) were used. The Kruskal-Wallis test was used for intergroup comparisons. Results: A total of 74 videos that met the inclusion criteria were included in the analysis. In terms of video quality, 68% were poor, 19% were moderate, and 13% were exceptional. Videos submitted by publishers with a medical background were much less popular (p < 0.05) than those submitted by publishers without a medical background. The video quality did not differ among those included in this study. Conclusions: Some videos on YouTube that are of real value are not as popular as those with low-quality content submitted by news agencies/media publishers. Furthermore, videos submitted by those with a medical background do not receive as much attention as others. It is important to acknowledge that video platforms should establish content and quality auditing mechanisms for videos. Furthermore, publishers should ensure that viewers receive accurate and complete knowledge and use more concise and accessible images or animations that are tailored to the audience.

Combined treatment of xyloglucan derivative hydrogel and anti-C5a receptor antibody in preventing peritoneal adhesion.

Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.

Application Value of the CT Scan 3D Reconstruction Technique in Maxillofacial Fracture Patients.

Purpose The aim of the study was to explore the application value of computerized tomography (CT) scan 3D reconstruction technology in maxillofacial fracture patients. Methods A total of 80 maxillofacial fracture patients who underwent surgical treatment in Shijiazhuang People's Hospital from January 2019 to January 2020 were enrolled. All of them received 128-slice spiral CT scans before surgery, and the images were subjected to multiplanar reconstruction (MRP) and volume reconstruction (VR). Results A total of 181 fractures were found in 80 patients with maxillofacial fractures. The detection rates of axial CT, MRP, and VR were 77.90% (141/181), 93.92% (170/181), and 97.79% (177/181), respectively. The detection rates of the four inspection methods were statistically different. Taking the findings of surgical anatomy as the gold standard, the sensitivity of MRP and VR for the diagnosis of maxillofacial fractures was 90.06% (163/170) and 95.56% (174/177), with no significant difference. Conclusion CT scan 3D reconstruction technology has a high application value in the clinical diagnosis and treatment of maxillofacial fracture patients.

Large-Scale Analysis of Fitness Cost of tet(X4)-Positive Plasmids in Escherichia coli.

Tigecycline is one of important antimicrobial agents for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence and prevalence of plasmid-mediated tigecycline resistance gene tet(X4) are threatening human and animal health. Fitness cost elicited by resistance plasmids is a key factor affecting the maintenance and transmission of antibiotic resistance genes (ARGs) in the host. A comparative analysis of the fitness cost of different types of tet(X4)-positive plasmids is helpful to understand and predict the prevalence of dominant plasmids. In this study, we performed a large-scale analysis of fitness cost of tet(X4)-positive plasmids origin from clinical isolates. These plasmids were successfully electroporated into a reference strain Escherichia coli TOP10, and a series of transformants carrying the tet(X) gene were obtained. The effects of tet(X4)-positive plasmids on the growth rate, plasmid stability, relative fitness, biofilm formation, and virulence in a Galleria mellonella model were evaluated. Consequently, we found that these plasmids resulted in varying degrees of fitness cost on TOP10, including delayed bacterial growth and attenuated virulence. Out of these plasmids, tet(X4)-harboring IncFII plasmids showed the lowest fitness cost on the host. Furthermore, by means of experimental evolution in the presence of commonly used drugs in clinic, the fitness cost of tet(X4)-positive plasmids was substantially alleviated, accompanied by increased plasmid stability. Collectively, our data reveal the differential fitness cost caused by different types of tet(X4)-positive plasmids and suggest that the wide use of tetracycline antibiotics may promote the evolution of plasmids.

A novel risk score for disease control prediction of chronic rhinosinusitis.

OBJECTIVES: To assess the impact of risk factors on the disease control among chronic rhinosinusitis (CRS) patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualised prediction model. DESIGN: A retrospective and nonconcurrent cohort study. SETTING AND PARTICIPANTS: A total of 325 patients with CRS from June 2018 to July 2020 at the First Affiliated Hospital of Sun Yat-sen University, the Third Affliated Hospital of Sun Yat-sen University, the Seventh Affiliated Hospital of Sun Yat-sen University. MAIN OUTCOMES MEASURES: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER) and peripheral blood eosinophil count (PBEC) and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and area under curve (AUC) were used to evaluate the forecast performance of the model. RESULTS: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. CONCLUSIONS: In this cohort study that included the asthma, AR, TER, PBEC, which had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualised reference for daily diagnosis and treatment.

A spiral cystic fibroma originating from left ventricular fascicular muscle: a case report.

BACKGROUND: In adults, cardiac fibromas are fairly rare, mostly round in shape, and few cases of ventricular fibromas of other morphology have been reported. CASE PRESENTATION: We report a case of a 47-year-old male patient admitted with recurrent nocturnal paroxysmal dyspnea, diagnosed by transthoracic cardiac ultrasound, transesophageal ultrasound, and computed tomography (CT) as a left ventricular occupancy with a spiral shape resembling a conch with a fixed base and a free distal end. CONCLUSION: This case reports a rare but noteworthy morphological features of the adult uncommon ventricular tumor pathological type. Furthermore, the patient had no notable postoperative issues and was followed up on for a year following surgery, with no residual tumors or arrhythmias discovered during the examination.