Exosomes, small extracellular vesicles ranging from 30 to 150 nm, are secreted by various cell types, including tumour cells. Recently, microRNAs (miRNAs) were identified to be encapsulated and hence protected from degradation within exosomes. These exosomal miRNAs can be horizontally transferred to target cells, in which they subsequently modulate biological processes. Increasing evidence indicates that exosomal miRNAs play a critical role in modifying the microenvironment of lung cancers, possibly facilitating progression, invasion, angiogenesis, metastasis and drug resistance. In this review, we summarize the novel findings on exosomal miRNA functions during lung cancer initiation and progression. In addition, we highlight their potential role and challenges as biomarkers in lung cancer diagnosis, prognosis and drug resistance and as therapeutic agents.

Background: Nocardia genus, a complex group of species classified to be aerobic actinomycete, can lead to severe concurrent infection as well as disseminated infection, typically in immunocompromised patients. With the expansion of the susceptible population, the incidence of Nocardia has been gradually growing, accompanied by increased resistance of the pathogen to existing therapeutics. However, there is no effective vaccine against this pathogen yet. In this study, a multi-epitope vaccine was designed against the Nocardia infection using reverse vaccinology combined with immunoinformatics approaches.Methods: First, the proteomes of 6 Nocardia subspecies Nocardia subspecies (Nocardia farcinica, Nocardia cyriacigeorgica, Nocardia abscessus, Nocardia otitidiscaviarum, Nocardia brasiliensis and Nocardia nova) were download NCBI (National Center for Biotechnology Information) database on May 1st, 2022 for the target proteins selection. The essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome proteins were selected for epitope identification. The shortlisted T-cell and B-cell epitopes were fused with appropriate adjuvants and linkers to construct vaccines. The physicochemical properties of the designed vaccine were predicted using multiple online servers. The Molecular docking and molecular dynamics (MD) simulation were performed to understand the binding pattern and binding stability between the vaccine candidate and Toll-like receptors (TLRs). The immunogenicity of the designed vaccines was evaluated via immune simulation.Results: 3 proteins that are essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome were selected from 218 complete proteome sequences of the 6 Nocardia subspecies epitope identification. After screening, only 4 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes that were antigenic, non-allergenic, and non-toxic were included in the final vaccine construct. The results of molecular docking and MD simulation showed that the vaccine candidate has a strong affinity for TLR2 and TLR4 of the host and the vaccine-TLR complexes were dynamically stable in the natural environment. The results of the immune simulation indicated that the designed vaccine had the potential to induce strong protective immune responses in the host. The codon optimization and cloned analysis showed that the vaccine was available for mass production.Conclusion: The designed vaccine has the potential to stimulate long-lasting immunity in the host, but further studies are required to validate its safety and efficacy.

Sepsis is a potentially life-threatening disease that results from a severe systemic inflammatory response due to infection. Mesenchymal stromal cell-derived small extracellular vesicles (MSC sEVs) are able to transfer bioactive molecules and have been demonstrated to play an important role in the pathophysiological process of sepsis. Herein the authors aimed to investigate the potential role and downstream molecular mechanism of MSC sEVs in sepsis. MSC sEVs were acquired by ultracentrifugation and then injected into a cecal ligation and puncture mouse model. The efficacy of MSC sEVs in both in vitro and in vivo models of sepsis was evaluated. MSC sEV therapy improved survival, reduced sepsis-induced inflammation, attenuated pulmonary capillary permeability and improved liver and kidney function in septic mice. In addition, the authors found that microRNA-21a-5p (miR-21a-5p) was highly enriched in MSC sEVs, could be transferred to recipient cells, inhibited inflammation and increased survival in septic mice. Furthermore, the authors demonstrated that MSC sEV miR-21a-5p suppressed inflammation by targeting toll-like receptor 4 and programmed cell death 4. The therapeutic efficacy of MSC sEVs was partially abrogated by transfection with miR-21a-5p inhibitors. Collectively, the authors' data suggest that miR-21a-5p-bearing MSC sEVs may be a prospective and effective sepsis therapeutic strategy.

Background: Computer-assisted and template-guided mandibular reconstruction provides higher accuracy and less variation than conventional freehand surgeries. The combined osteotomy and reconstruction pre-shaped plate position (CORPPP) technique is a reliable choice for mandibular reconstruction. This study aimed to evaluate the accuracy of CORPPP-guided fibular flap mandibular reconstruction and analyze the possible causes of the deviations.Patients and Methods: From June 2015 to December 2016, 28 patients underwent fibular flap mandibular reconstruction. Virtual planning and personalized CORPPP-guided templates were applied in 15 patients while 13 patients received conventional freehand surgeries. Deviations during mandibulectomy and fibular osteotomy, and overall and triaxial deviation of the corresponding mandibular anatomical landmarks were measured by superimposing the pre- and postoperative virtual models.Results: The deviation of the resection line and resection angle was 1.23 ± 0.98 mm and 4.11° ± 2.60°. The actual length of fibula segments was longer than the designed length in 7 cases (mean: 0.35 ± 0.32 mm) and shorter in 22 cases (mean: 1.53 ± 1.19 mm). In patients without ramus reconstruction, deviations of the ipsilateral condylar head point (Co.), gonion point (Go.), and coracoid process point (Cor.) were 6.71 ± 3.42 mm, 5.38 ± 1.71 mm, and 11.05 ± 3.24 mm in the freehand group and 1.73 ± 1.13 mm, 1.86 ± 0.96 mm, and 2.54 ± 0.50 mm in the CORPPP group, respectively, with significant statistical differences (p < 0.05). In patients with ramus reconstruction, deviations of ipsilateral Co. and Go. were 9.79 ± 4.74 mm vs. 3.57 ± 1.62 mm (p < 0.05), and 15.17 ± 6.53 mm vs. 4.36 ± 1.68 mm (p < 0.05) in the freehand group and CORPPP group, respectively.Conclusion: Mandibular reconstructions employing virtual planning and personalized CORPPP-guided templates show significantly higher predictability, convenience, and accuracy of mandibular reconstruction compared with conventional freehand surgeries. However, more clinical cases were required for further dimensional deviation analysis. The application and exploration of clinical practice would also continuously improve the design of templates.

Coronavirus disease 2019 (COVID-19) has rapidly swept across the world. This study aimed to explore the relationship between the chest CT findings and clinical characteristics of COVID-19 patients....

Objectives: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan City and rapidly spread across the world. The clinical characteristics of affected patients in different regions and populations may differ. Thus, this study aimed to identify the characteristics of the disease to provide an insight about the prevention and treatment of COVID-19. Methods: Data on the demographic characteristics and clinical findings of the patients admitted at the First Hospital of Changsha from January 1, 2020 to February 10, 2020 were assessed. Results: In this study, there were 8 (3.8%) asymptomatic, 21 (10.0%) mild upper respiratory tract infection (URTI), and 180 (86.1%) pneumonia cases. In total, 47 (22.5%) patients resided in Wuhan, and 45 (21.5%) had recently traveled to Wuhan before disease onset. Moreover, 19 (9.1%) had contact with people from Wuhan, and 69 (33.0%) were family cluster cases. The median incubation period was approximately 6.3 (range: 1.0–20.0) days. Fever and cough were the most common initial symptoms: 99 (49.3%) patients presented with fever, without cough; 59 (29.4%) with cough, without fever; and 33 (16.4%) with both fever and cough. Conclusion: The symptoms of patients with COVID-19 were relatively mild outside Wuhan, and family cluster was a remarkable epidemic characteristic. Special attention should be paid to asymptomatic patients.