Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and main results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. Trial registration: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http://www.medresman.org

Carbapenem-resistant Acinetobacter baumannii (CRAB) tops the list of threats to human health. Studies exploring predictors of mortality in patients with CRAB infection produced conflicting results. A systematic search of the PubMed, Embase, and the Cochrane Library databases was performed from inception to June 2018 to identify studies reporting mortality predictors in patients infected with CRAB. Two authors independently assessed trials for inclusion and data extraction. A total of 19 observational studies were enrolled in this study. Factors associated with mortality of patients infected with CRAB were inappropriate empirical antimicrobial treatment (odds ratio [OR], 5.04; 95% confidence interval [CI], 2.56-9.94), septic shock (OR, 5.65; 95% CI, 2.35-13.57), chronic liver disease (OR, 2.36; 95% CI, 1.33-4.16), chronic renal disease (OR, 2.02; 95% CI, 1.37-2.99), hypertension (OR, 1.74; 95% CI, 1.08-2.80), neutropenia (OR, 3.31; 95% CI, 1.25-8.77), immunosuppressant use (OR, 3.15; 95% CI, 1.94-5.11), total parenteral nutrition (OR, 1.66; 95% CI, 1.08-2.56), and intubation (OR, 5.03; 95% CI, 2.33-10.87). Acute Physiology and Chronic Health Evaluation II score at admission and Pitt bacteremia score at the onset of CRAB bacteremia were higher in nonsurvivors. Our study suggests that severity of baseline condition and receiving inappropriate experience antibiotic therapy are major risk factors for higher mortality in patients with CRAB infections. These findings may help clinicians to take appropriate preventive measures and decrease mortality in such patients.

Pulmonary infection is a heterogeneous and complex infectious disease with high morbidity and mortality worldwide. In clinical practice, a considerable proportion of the etiology of pulmonary infection is unclear, microbiological diagnosis being challenging. Metagenomic next-generation sequencing detects all nucleic acids in a sample in an unbiased manner, revealing the microbial community environment and organisms and improving the microbiological detection and diagnosis of infectious diseases in clinical settings.

Plant-derived extracellular vesicles (PDEVs) have shown remarkable potential as sustainable, green, and efficient drug delivery nanocarriers. As natural nanoparticles containing lipids, protein, nucleic acids and secondary metabolites, they have received widespread attention as a replacement for mammalian exosomes in recent years. In this review, the advances in isolation, identification, composition, therapeutic effect, and clinical application prospect were comprehensively reviewed, respectively. In addition, the specific modification strategies have been listed focusing on the inherent drawbacks of the raw PDEVs like low targeting efficiency and poor homogeneity. With emphasis on their biology mechanism in terms of immune regulation, regulating oxidative stress and promoting regeneration in the anti-inflammatory field and application value demonstrated by citing some typical examples, this review about PDEVs would provide a broad and fundamental vision for the in-depth exploration and development of plant-derived extracellular vesicles in the in-vivo anti-inflammation and even other biomedical applications.

Background: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice. Methods: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice. Results: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22. Conclusion: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.

Recently, development of drug delivery systems for accurate delivery of antitumor drugs to tumor sites to improve their antitumor efficacy has attracted great interest in the area of cancer immunotherapy. In this report, an intelligent biodegradable hollow manganese dioxide (HMnO₂) nanoparticle (NP) with a human umbilical cord mesenchymal stem cell (hUC-MSC) membrane coating was designed to exert efficient chemo-immunotherapy for cancer treatment. A TAT peptide-modified membrane structure was constructed for nuclear targeting. Our findings showed that this new nanoreactor inherited the active targeting capability of MSCs and exhibited tumoritropic accumulation significantly at the cancerous parts. Compared with other formulations, intravenous injection of the NPs markedly inhibited tumor growth, relapse, and metastasis. Moreover, we found that the NPs effectively boosted dendritic cell maturation and recruited effector T cells into tumors. Overall, this work demonstrates the great potential of applying MSC membrane-coated manganese dioxide NPs as nucleus-targeting nanocarriers in cancer chemo-immunotherapy.