Human monoclonal antibodies against Staphylococcus aureus A protein identified by high-throughput single-cell sequencing of phase I clinical volunteers' B cells.

Methicillin-resistant Staphylococcus aureus, poses a significant threat through infections in both community and hospital settings. To address this challenge, we conducted a phase I clinical trial study involving a recombinant Staphylococcus aureus vaccine. Utilizing peripheral blood lymphocytes from 64 subjects, we isolated antigen-specific memory B cells for subsequent single-cell sequencing. Among the 676 identified antigen-binding IgG1+ clones, we selected the top 10 antibody strains for construction within expression vectors. Successful expression and purification of these monoclonal antibodies led to the discovery of a highly expressed human antibody, designated as IgG-6. This antibody specifically targets the pentameric form of the Staphylococcus aureus protein A (SpA5). In vivo assessments revealed that IgG-6 provided prophylactic protection against MRSA252 infection. This study underscores the potential of human antibodies as an innovative strategy against Staphylococcus aureus infections, offering a promising avenue for further research and clinical development.

Six Years of Complaints Issued by Patients at a Laser Treatment Center in a Plastic Surgery Hospital.

Background: Patient complaints can provide valuable feedback regarding the objective deficiencies of medical services. There are few studies on the complaints of patients receiving photoelectric therapy, so this study aims to understand the expectations and requirements of patients by analyzing the complaints of patients receiving photoelectric therapy. Methods: The complaints of patients who underwent photoelectric therapy were retrospectively examined. Authors plan to analyze treatment items, complaint contents, appeals, time trend regarding the number of complaints, and economic compensation. Results: Fifty-four patients were involved in the study in total, and all of them were included. According to the standardized coding classification of complaints by Reader et al., the number of clinical, management and relationship complaints were 36 (59.02%), 14 (22.95%), and 11 (18.03%), respectively. These were divided among the categories of quality (31.15%), safety (27.87%), institutional issues (22.95%), communication (8.20%), and humaneness/caring (9.84%); with the most common subcategories involving treatment (31.15%) and safety incidents (24.59%). The patients' demands involved 20 cases (32.26%) requesting a refund of their medical expenses, 16 (25.81%) issuing a warning, 15 (24.19%) requesting compensation for loss, 10 (16.13%) requiring free repair or consultation, and 1 (1.61%) demanding an apology. Eventually, financial compensation was provided to the patients in eight of the cases. At a significance level of P = 0.05, even if the number of annual complaints increased over time, the increasing trend was not significant. Conclusions: Patient complaints in photoelectric therapy were most commonly clinical in nature. Specifically, quality and safety concerns are the main complaints.

Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge.

The ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). The pSpike/PP-sNp not only displays superior gene transfection and favorable biocompatibility in the mouse airway, but also promotes a tripartite immunity consisting of systemic, cellular, and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, immunization with pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp is a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.

Intranasal Vaccination with rePcrV Protects against Pseudomonas aeruginosa and Generates Lung Tissue-Resident Memory T Cells.

Tissue-resident memory T (TRM) cells are immune sentinels that bear a key role in the local immune system and rapidly respond to infection. Our previous studies showed that mucosal immunization via intranasal pathways was more effective than intramuscular route. However, the mechanism of enhanced protective immunity remains unclear. Here, we formulated a Pseudomonas aeruginosa vaccine composed of type III secretion protein PcrV from P. aeruginosa and curdlan adjuvant and then administered by the intranasal route. Flow cytometry and immunofluorescence staining showed that the ratio of CD44+CD62L-CD69+CD4+ TRM cells induced by this vaccine was significantly increased, and IL-17A production was notably enhanced. Further analysis revealed that vaccinated mice can protect against the P. aeruginosa challenge even after administration with FTY720 treatment. What is more, our results showed that CD4+ TRM might be involved in the recruitment of neutrophils and provided partial protection against Pseudomonas aeruginosa. Taken together, these data demonstrated that CD4+ TRM cells were elicited in lung tissues after immunization with rePcrV and contributed to protective immunity. Furthermore, it provided novel strategies for the development of vaccines for P. aeruginosa and other respiratory-targeted vaccines.

Incision and flap design during total auricular reconstruction using a 2-stage strategy.

BACKGROUND: Total auricular reconstruction is a challenge for plastic surgeons. Expanded flap method and Nagata's method with autologous costal cartilage are two leading techniques for ear reconstruction. And a two-stage strategy of expanded flap method received attention. In the present study, we report the incision and flap design of this strategy. METHODS: In the first stage, an 80 mL kidney-shaped expander was inserted in the mastoid region with the larger pole superiorly. The expander pocket was dissected subcutaneously in the scalp area and subfascially in the lower third region. In the second stage, the expander was removed from a Y-shaped lobule incision on the remanent ear. Then the remnant ear was separated into three flaps: the posterior skin flap, anterior skin flap, and lobule flap. When the framework was fabricated, the base frame and the underlying pad, which enhanced the projection, were fixed together as a whole to provide a more prominent appearance. The framework was totally wrapped into the expanded single flap without free skin grafting. Lobule transposition and tragus construction were performed simultaneously instead of a third-stage surgery. The recipient bed of rotated lobule was resected only to the epidermal layer and the subcutaneous layer was preserved to avoid central necrosis. RESULTS: A total of 21 patients received this strategy to reconstruct ear. With 3 months to 1.5 years of follow-up, 19 patients (90.5%) were satisfied with the reconstructed ears. 3 patients (14.3%) required further modification of reconstructed ear. No serious complications occurred during the procedures. CONCLUSIONS: With a Y-shaped incision, three-flap design of remanent ear and lobule rotation to an epidermal-removal area, tissue expander removal and modification of remanent ear can be performed effectively to avoid necrosis and an extra operation.

A novel two-stage strategy combing tissue expansion and Nagata`s technique for total auricular reconstruction.

BACKGROUND: This study was performed to explore the clinical application of the Nagata's technique for combing tissue expansion in auricular reconstruction. METHODS: The auricular reconstruction was performed in two surgical stages. At the first stage, an 80 ml expander was inserted in the mastoid region after preoperative evaluation. After a gradual expansion period and nearly 2-month rest time, the flap achieved the appropriate area and thickness. At the second stage, the expander was removed and a three-layer cartilage framework was inserted into the pocket through a Y-shaped lobule incision, and the earlobe and tragus were rebuild simultaneously. RESULTS: From 2012 to 2016, 104 microtia patients underwent auricular reconstruction with this method in our hospital. Patients were followed up for between 6 months and 2 years. Ninety-six patients and their families were satisfied with the results, especially the clear outline, appropriate color, good projection, and the symmetry of bilateral ears. Complications of ischemic necrosis of the distal earlobe and skin of the concha cavity occurred in two cases, hematoma after the first stage occurred in two cases, and four patients needed further restorations. CONCLUSIONS: A novel two-stage strategy combing tissue expansion and Nagata's technique is an effective and efficient technique for auricular reconstruction with satisfying medium-term results.

An efficient electrochemiluminescence amplification strategy via bis-co-reaction accelerator for sensitive detection of laminin to monitor overnutrition associated liver damage.

With the world wildly improvement in dietary and nutrition status, it couldn't be ignored that the chronic liver disease (CLD) resulted from the overnutrition. In order to estimate nutrition status for healthy living, an efficient and sensitive electrochemiluminescence (ECL) sandwich immunosensor of laminin (LN), a marker of CLD, was proposed for early diagnosis of CLD. In this work, the anodic ECL behavior of perylene derivative using H2O2 as co-reactant was demonstrated and the possible ECL mechanism was proposed. Furthermore, a significantly amplified ECL response could be obtained via Ag and Fe-Fe2O3 nanoparticles as bis-co-reaction accelerator. As a result, the proposed ECL immunosensor performed good sensitivity and accuracy with a detection limit down to 0.03pg/mL. Moreover, this immunosensor was successfully employed to monitor patient serum, which exhibited an alternative avenue for the early diagnosis of other diseases via proteins, nucleotide sequence, microRNA and cells.