Association of atopy with disease severity in children with Mycoplasma pneumoniae pneumonia.

Background: Mycoplasma pneumoniae pneumonia (MPP) is common among children, but the impact of atopy on MPP severity in children is unknown. This study investigated whether atopic vs. nonatopic children had greater MPP severity. Methods: Retrospective analysis was conducted on 539 (ages 3-14 years) patients who were hospitalized in the First Affiliated Hospital of Anhui Medical University for MPP between January 2018 and December 2021, 195 were atopic and 344 were nonatopic. Of them, 204 had refractory MPP, and 335 had general MPP. And of atopic children, 94 had refractory MPP, and 101 had general MPP. Data on demographic and clinical characteristics, laboratory findings, clinical treatments were analyzed. Results: Significantly more boys with MPP were atopic than nonatopic (P < 0.05). More atopic (than nonatopic) children presented with prolonged fever and hospitalization, severe extra-pulmonary complications, asthma attaking, steroid and oxygen treatment, and increased IgE levels (all P < 0.05). In atopic (vs. nonatopic) children with MPP, the incidence of sputum plugs under the fiberoptic bronchoscopy and lobar pneumonia was significantly increased and required bronchoscopy-assisted and steroid therapy. Compared with nonatopic children, more atopic children developed refractory MPP (P < 0.05). Prolonged fever and hospitalization, severe extra-pulmonary complications, lymphocyte count, procalcitonin and lactate dehydrogenase levels, and percentages of atopy were all significantly higher (P < 0.05) among children with refractory MPP vs. general MPP. Moreover, Prolonged fever and hospitalization, lymphocyte count, procalcitonin and lactate dehydrogenase levels, and the treantment of steroid were all significantly higher (P < 0.05) among atopic children with refractory MPP vs. general MPP. Spearman correlation analysis showed strong associations between atopy and male sex, length of hospital stay, fever duration, IgE level, wheezing, lobar pneumonia, refractory MPP, and treatment with oxygen, hormones or bronchoscopy (P < 0.05). Conclusions: Atopy may be a risk factor for and was positively correlated with the severity of MPP in children.

H2S-removing UiO-66 MOFs for sensitized antibacterial therapy.

Antibiotic tolerance is implicated in difficult-to-treat infections and the development and spread of antibiotic resistance. The high storage capacities and excellent biocompatibilities of UiO-66-based metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. In view of hydrogen sulfide (H2S) having been associated with the development of intrinsic resistance to antibacterial agents, we designed a strategy to potentiate existing antibiotics by eliminating bacterial endogenous H2S. We efficiently fabricated an antibiotic enhancer Gm@UiO-66-MA to remove bacterial H2S and sensitize an antibacterial by modifying UiO-66-NH2 with maleic anhydride (MA) and then loading it with gentamicin (Gm). UiO-66-MA achieved the removal of bacterial endogenous H2S and the destruction of bacterial biofilm by selectively undergoing Michael addition with H2S. Moreover, Gm@UiO-66-MA further enhanced the susceptibility of tolerant E. coli to Gm after reducing bacterial intracellular H2S levels. An in vivo skin wound healing experiment confirmed that Gm@UiO-66-MA could greatly reduce the risk of bacterial reinfection and accelerate wound healing. Overall, Gm@UiO-66-MA offers a promising antibiotic sensitizer for minimizing bacterial resistance and a therapeutic strategy for tolerant bacteria-related refractory infections.

Regulatory relationship between macrophage autophagy and PVL-positive methicillin-resistant Staphylococcus aureus.

The present study intends to clarify the hypothesis that PVL-positive Methicillin-resistant S. aureus strain (PVL+-MRSA)-infected macrophages regulate autophagy and thus in turn inhibit phagocytosis through the in vitro and in vivo experiments. The autophagy of mouse macrophage cell line RAW264.7 was observed by fluorescence microscopy, and counted based on the number of each cell dot-like structure GFP-LC3. The protein levels of the phagocytic factors associated with autophagy were determined by western blotting. The phagocytosis of RAW264.7 on MRSA was determined by counting the colony. The clinically isolated and identified PVL+-MRSA strain was used to infect BALB/c mice (left nasal drip) to establish a mouse pneumonia model. PVL+-MRSA mice were then treated with 3-MA or linezolid. Bronchoalveolar lavage fluid (BALF) from mice was collected for macrophage counting by Flow cytometry assay. The right lung was aseptically isolated for counting the amount of bacteria. The results showed that PVL+-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA and aggravated by rapamycin. Exogenous rPVL administrated into PVL--MRSA-infected macrophages caused the autophagy of macrophage. Exogenous rPVL, particularly A-Luk S-PV, administrated into macrophages also caused the autophagy of macrophage, which was reversed by PMX53, a C5aR antagonist. In a mouse pneumonia model, PVL+-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA or linezolid. In conclusion, this study indicated PVL+-MRSA regulated macrophage autophagy, which in turns inhibit the phagocytosis of S. aureus by macrophage. This study may provide a potential target against S. aureus infection.

A gentamicin-thioctic acid multifunctional hydrogel for accelerating infected wound healing.

Bacterial infections remain a major concern during wound healing and tissue bonding. The excessive proliferation of bacteria will seriously hinder the repair of the wound and even lead to death. Generally, surgical sutures might cause damage to the surrounding tissues and inevitable infection due to the unfixed shape of the wound. Thus, it is urgent to develop novel antibacterial skin dressing with self-healing and strong adhesion properties. Herein, we prepared an antibacterial and self-healable hydrogel with strong adhesion activity through natural small molecules, including thioctic acid TA and gentamicin (GM). The rapid ring-opening-polymerization of the TA (PTA) forms the backbone of macromolecules, and the functional hydrogel was constructed with the crosslinking of GM, termed as G-PTA, which offers hydrogen bonding interactions between the amino and hydroxyl groups of GM and carboxylic group side chains of poly(TA). The synthesized hydrogel exhibited rapid self-healing ability and strong tissue adhesion due to the internal dynamic disulfide bonds and multiple hydrogen bonds. Importantly, the introduction of GM enabled the G-PTA hydrogel to sustainably release antibiotics and exhibit a durative antibacterial effect with the degradation of PTA, which further shorten the therapeutic time and enhance tissue regeneration in a wound infection model. The in vitro and in vivo experiments demonstrate that the G-PTA hydrogel has potential as a surgical antibacterial biological adhesive, especially for bacterial wound infections.

Epidemiological and clinical features of SARS-CoV-2 cluster infection in Anhui Province, Eastern China.

BACKGROUND: COVID-19 has spread worldwide and become a pandemic. We report the epidemiological and clinical characteristics of cluster infections. METHODS: Data of clustered cases were retrieved from the public health emergency monitoring information system of China. We analyzed the incubation period, generation gap, secondary attack rate, and viral load in various grouped cases. RESULTS: A total of 60 COVID-19 infection clusters including 226 patients and 19 asymptomatic cases involving four generations were analyzed. With the increase of transmission generations, secondary attack rate decreased (P＜0.001) and severity alleviated (P = 0.008). The median incubation period and intergenerational interval were 9 and 6 days, respectively. The secondary attack rate was 7.1% in the index cases, 5.0% in the first generation, 1.0% in the second generation, and 4.7% overall. Severe cases were seen more in the index (13, 65%) and first generation (7, 35%) ones, who had a significantly higher viral load than the mild and moderate ones. CONCLUSIONS: With the increase of transmission generation, secondary infection rate and severity decreased. Severe patients had a higher virus load. Patients in the incubation period and asymptomatic carriers were potential infection sources who might play an important role in transmission.

Evaluation of several immune and inflammatory indicators and their association with alopecia areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder and chronic recurrent inflammatory disease that results in non-scarring hair loss. OBJECTIVES: Our aim is to investigate several parameters related to autoimmunity and inflammation in AA patients and to evaluate their association with this disease. METHODS: This study included a total of 672 eligible AA patients and 580 age- and sex-matched healthy individuals who were treated at a third-class hospital in Hefei from January 2016 to May 2020. Data for serum C-reactive protein (CRP), 25-hydroxy vitamin D (25(OH)D), T3, T4, thyroid-stimulating hormone (TSH), thyroid antibodies (TPOAbs and TGAbs), antinuclear antibodies (ANA), complements (C3, C4), and several immunoglobulins (IgA, IgM, and IgG) were collected in this study. RESULTS: Regarding autoimmune-related functional indicators, there were no statistically significant differences between TSH, TGAbs, C3, C4, IgA, IgM, and IgG levels between AA patients and healthy controls. Only T3, T4, TPOAbs, and ANA values were significantly abnormal in the AA group compared with the healthy individuals (p < 0.05). In addition, the mean serum 25(OH)D concentration was significantly lower in the patient group than that in control group (p < 0.05), and serum CRP was significantly increased (p < 0.05). CONCLUSION: Although the etiopathogenesis of AA is not clear, the importance of monitoring the levels of T3, T4, TPOAbs, ANA, and 25 (OH)D in AA cases is indispensable.

Nano-metal-organic-frameworks for treating H2O2-Secreting bacteria alleviate pulmonary injury and prevent systemic sepsis.

As a vital bacteria-secreted toxin, hydrogen peroxide (H2O2) can destroy infected tissues and increase vascular permeability, leading to life-threatening systemic bacteremia or sepsis. No strategy that can alleviate H2O2-induced injury and prevent systemic sepsis has been reported. Herein, as a proof of concept, we demonstrate the use of H2O2-reactive metal-organic framework nanosystems (MOFs) for treating H2O2-secreting bacteria. In mice infected with Streptococcus pneumoniae (S. pneumoniae) isolated from patients, MOFs efficiently accumulate in the lungs after systemic administration due to infection-induced alveolar-capillary barrier dysfunction. Moreover, MOFs sequester pneumococcal H2O2, reduce endothelial DNA damage, and prevent systemic dissemination of bacteria. In addition, this nanosystem exhibits excellent chemodynamic bactericidal effects against drug-resistant bacteria. Through synergistic therapy with the antibiotic ampicillin, MOFs eliminate over 98% of invading S. pneumoniae, resulting in a survival rate of greater than 90% in mice infected with a lethal dose of S. pneumoniae. This work opens up new paths for the clinical treatment of toxin-secreting bacteria.

Voluntary-Opsonization-Enabled Precision Nanomedicines for Inflammation Treatment.

Nanomedicines that target specific blood cells represent an emerging strategy to improve drug biodistribution. However, the protein corona usually disrupts nanomedicine targeting to cells and tissues. Herein, instead of exploring synthetic methods to mitigate the impact of the protein corona, its natural interactions with blood cells are leveraged and turn the protein corona into an active ingredient in treating lung inflammation. It is discovered that molecularly engineered liposomes with inverse phosphocholine lipids rapidly enrich complement fragment iC3b by "voluntary opsonization," which triggers neutrophil hijacking through complement receptor 3 phagocytosis. This neutrophil targeting is cell-state dependent as only those activated by acute inflammation display efficient neutrophil reconstruction. The liposome-loaded neutrophils migrate across the alveolar-capillary barrier, accumulate in the inflamed lung parenchyma within hours, and release their payloads to kill the bacteria. This work shows that, in addition to biological cells, the protein corona can be a new platform for active and precision nanomedicine.