S100A9-/- alleviates LPS-induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the TLR4/MyD88/NFκB signaling axis.

Acute lung injury (ALI) is characterized by pulmonary diffusion abnormalities that may progress to multiple-organ failure in severe cases. There are limited effective treatments for ALI, which makes the search for new therapeutic avenues critically important. Macrophages play a pivotal role in the pathogenesis of ALI. The degree of macrophage polarization is closely related to the severity and prognosis of ALI, and S100A9 promotes M1 polarization of macrophages. The present study assessed the effects of S100A9-gene deficiency on macrophage polarization and acute lung injury. Our cohort study showed that plasma S100A8/A9 levels had significant diagnostic value for pediatric pneumonia and primarily correlated with monocyte-macrophages and neutrophils. We established a lipopolysaccharide (LPS)-induced mouse model of acute lung injury and demonstrated that knockout of the S100A9 gene mitigated inflammation by suppressing the secretion of pro-inflammatory cytokines, reducing the number of inflammatory cells in the bronchoalveolar lavage fluid, and inhibiting cell apoptosis, which ameliorated acute lung injury in mice. The in vitro and in vivo mechanistic studies demonstrated that S100A9-gene deficiency inhibited macrophage M1 polarization and reduced the levels of pulmonary macrophage chemotactic factors and inflammatory cytokines by suppressing the TLR4/MyD88/NF-κB signaling pathway and reversing the expression of the NLRP3 pyroptosis pathway, which reduced cell death. In conclusion, S100A9-gene deficiency alleviated LPS-induced acute lung injury by inhibiting macrophage M1 polarization and pyroptosis via the TLR4/MyD88/NFκB pathway, which suggests a potential therapeutic strategy for the treatment of ALI.

Cardiac injury in hospitalized patients with severe fever and thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with a high fatality rate. Cardiac injury in SFTS patients is a major concern. This study aimed to evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with novel Bunyavirus. Cardiac injury was defined as the presence of any of the following abnormalities: (1) blood levels of cardiac biomarkers (creatine kinase-MB, troponin-I, B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide); (2) new abnormalities in electrocardiography. The 203 SFTS patients were included in the final analysis. The proportion of SFTS patients developing cardiac injury during hospitalization was 71.4% (145/203). Compared with the uninjured group, the cardiac injury group had the severity of cardiac injury was underscored by higher median hospital costs (31420 vs. 12911, p < 0.001), higher proportion of intensive care units admissions (13.1% vs. 3.4%, p = 0.041), and higher hospital mortality rate (33.8% vs. 6.9%, p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality during hospitalization (hazards ratio, 7.349; 95% CI: 2.352-22.960). Cardiac injury is common among hospitalized SFTS patients, and it is associated with higher risk of mortality.

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.

ACCI could be a poor prognostic indicator for the in-hospital mortality of patients with SFTS.

This study aims to evaluate the predictive role of age-adjusted Charlson comorbidity index (ACCI) scores for in-hospital prognosis of severe fever in thrombocytopenia syndrome (SFTS) patients. A total of 192 patients diagnosed with SFTS were selected as the study subjects. Clinical data were retrospectively collected. Receiver operating characteristic curves were used to evaluate the diagnostic value of ACCI for the mortality of SFTS patients, and Cox regression models were used to assess the association between predictive factors and prognosis. The 192 SFTS patients were divided into two groups according to the clinical endpoints (survivors/non-survivors). The results showed that the mortality of the 192 hospitalized SFTS patients was 26.6%. The ACCI score of the survivor group was significantly lower than that of the non-survivor group. Multivariate Cox regression analysis showed that the increased ACCI score was a significant predictor of poor prognosis in SFTS. Kaplan-Meier survival analysis showed that SFTS patients with an ACCI >2.5 had shorter mean survival times, indicating a poor prognosis. Our findings suggest that ACCI, as an easy-to-use clinical indicator, may offer a simple and feasible approach for clinicians to determine the severity of SFTS.

A Single-Component Dual Donor Enables Ultrasound-Triggered Co-release of Carbon Monoxide and Hydrogen Sulfide.

The development of dual gasotransmitter donors can not only provide robust tools to investigate their subtle interplay under pathophysiological conditions but also optimize therapeutic efficacy. While conventional strategies are heavily dependent on multicomponent donors, we herein report an ultrasound-responsive water-soluble copolymer (PSHF) capable of releasing carbon monoxide (CO) and hydrogen sulfide (H2 S) based on single-component sulfur-substituted 3-hydroxyflavone (SHF) derivatives. Interestingly, sulfur substitution can not only greatly improve the ultrasound sensitivity but also enable the co-release of CO/H2 S under mild ultrasound irradiation. The co-release of CO/H2 S gasotransmitters exerts a bactericidal effect against Staphylococcus aureus and demonstrates anti-inflammatory activity in lipopolysaccharide-challenged macrophages. Moreover, the excellent tissue penetration of ultrasound irradiation enables the local release of CO/H2 S in the joints of septic arthritis rats, exhibiting superior therapeutic efficacy without the need for any antibiotics.

Associated Risk Factors and Diagnostic Value of Fiberoptic Bronchoscopy for Protracted Bacterial Bronchitis in Children.

Objective: Untreated protracted bacterial bronchitis (PBB), a chronic wet cough prevalent in children, may lead to chronic suppurative lung disease. However, clinical diagnostic criteria are currently nonspecific; thus, PBB may be misdiagnosed. Thus, we assessed the diagnostic value of fiberoptic bronchoscopy (FOB) and the risk factors associated with PBB. Methods: Children with chronic cough at The First Affiliated Hospital of Anhui Medical University from January 2015 to May 2020 were enrolled and allocated to a suspected PBB (n = 141) or a non-PBB (n = 206) group. All children underwent extensive laboratory, chest imaging, and allergen tests. Children with suspected PBB underwent FOB with bronchoalveolar lavage; lavage and sputum samples were cultured. Results: All 347 children had a chronic wet cough for approximately 2 months. Of 141 children with suspected PBB, 140 received FOB with bronchoalveolar lavage. Visible tracheal changes included pale mucosa, mucosal congestion, edema, swelling, and increased secretions attached to the wall. Sputum was visible primarily in the left main bronchus (78.7%), left lower lobe (59.6%), right upper lobe (62.4%), and right lower lobe (64.5%). Sputum properties and amounts significantly differed between children with vs. without PBB (P < 0.05). Dermatophagoides (odds ratio (OR), 2.642; 95% CI, 1.283-5.369), milk protein (OR, 2.452; 95% CI, 1.243-4.836) allergies, and eczema (OR, 1.763; 95% CI, 1.011-3.075) were risk factors significantly associated with PBB. Conclusion: Dermatophagoides, milk protein, and eczema were associated with an increased risk of PBB. Sputum distribution and tracheal wall changes observed through FOB may distinguish PBB and assist in its diagnosis.

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.

Association of sodium-glucose cotransporter 2 inhibitors with cardiovascular outcome and safety events: A meta-analysis of randomized controlled clinical trials.

Background: The clinical benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for preventing and treating cardiovascular events remains controversial. We aimed to study the effect of SGLT2 inhibitors on cardiovascular outcomes and safety events, giving particular attention to the benefits in subgroups of patients with different diseases. Method: Randomized controlled trials (RCTs) reporting cardiovascular outcomes following the administration of SGLT2 inhibitors and placebo were included in this study. Cardiovascular outcomes included all-cause death, major adverse cardiovascular events (MACEs), cardiovascular (CV) death, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF). We also focused on the cardiovascular benefits of SGLT2 inhibitor application in subgroups of patients with different diseases, including type 2 diabetes (T2D), heart failure (HF), high risk of atherosclerotic cardiovascular disease (ACD), diagnosed ACD, and chronic kidney disease (CKD). Safety events associated with SGLT2 inhibitors, including acute kidney injury (AKI), diabetic ketoacidosis (DKA), hypoglycemia, urinary tract infection, thromboembolic event, bone fracture, volume depletion, and amputation, were also reported. Results: This meta-analysis included 15 RCTs with 78,212 participants. SGLT2 inhibitors reduced the risk of all-cause death (RR 0.89; 95% CI: 0.85-0.94; I2 = 32%; p < 0.01), CV death (RR 0.87; 95% CI: 0.82-0.93; I2 = 11%; p < 0.01), MACEs (RR 0.89; 95% CI: 0.84-0.94; I2 = 46%; p < 0.01), HHF (RR 0.70; 95% CI: 0.66-0.74; I2 = 0%; p < 0.01), and AKI (RR 0.81; 95% CI: 0.73-0.90; I2 = 0%; p < 0.01) but increased the risk of DKA (RR 2.56; 95% CI: 1.72-3.80; I2 = 0%; p < 0.01). However, no apparent benefit in MI and stroke was observed between the SGLT2 inhibitor and control groups. SGLT2 inhibitors reduced the risk of all-cause death, MACEs, CV death, and HHF in diabetic patients; reduced the risk of all-cause death, MACEs, CV death, MI, and HHF in primary prevention; reduced the risk of all-cause death, CV death, and HHF in patients with ACD and HF; and reduced the risk of MACEs, CV death, and HHF in patients with CKD. Conclusion: SGLT2 inhibitors have a positive effect in reducing the risk of all-cause death, CV death, MACE, HHF, and AKI and increasing the risk of DKA. The application of SGLT2 inhibitors in the primary prevention of ACD also has certain clinical benefits in reducing MI. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306490].

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.

Ultrasound-Mediated Release of Gaseous Signaling Molecules for Biomedical Applications.

Although nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S) have been considered as notorious gas pollutants for decades, they are considered as endogenous gaseous signaling molecules (GSMs), which have been widely recognized for their important signaling functions and prominent medical applications in human physiology. To achieve local delivery of GSMs to optimize therapeutic efficacy and reduce systemic side effects, stimuli-responsive nanocarriers have been successfully developed. Among them, ultrasound is considered as an attractive theranostic modality that can be used to track drug carriers, trigger drug release, and improve drug deposition, etc. In this minireview, recent achievements in designing ultrasound-responsive nanocarriers for the controlled delivery of GSMs and their biomedical applications are summarized. This emerging research direction enables the controlled delivery of GSMs to deep tissues, and the combination of ultrasound imaging techniques offers many possibilities for the fabrication of new theranostic platforms.

Retrospective analysis of clinical characteristics and related influencing factors of Kawasaki disease.

To compare the clinical characteristics of complete Kawasaki disease (KD) and incomplete Kawasaki disease (IKD), and analyze the possible risk factors of coronary artery lesion (CAL) in KD. The clinical data of 139 children with KD admitted to the hospital from January 2016 to June 2022 were analyzed retrospectively. The differences of clinical characteristics between children with KD and children with IKD were compared. The risk factors of CAL were analyzed using univariate and multivariate logistic regression. Comparison of clinical characteristics between KD and IKD groups, the results showed there was significant difference in terms of conjunctival congestion, rash, lymph node enlargement, hand and foot redness, intravenous immune globulin non reaction and fever time (P < .05). Comparison of laboratory indicators between 2 groups, the results showed that there was significantly difference in the levels of neutrophils (P < .05). 15 cases (15.31%) in KD group were complicated with CAL, and 17 cases (41.46%) in IKD group were complicated with CAL, and the results showed there was a significant difference between the 2 groups (P < .05). Univariate analysis showed that the age and Hb of children with CAL were lower than those of children with nCAL, while C-reactive protein, NT-proBNP, NEUT, and ESR were higher than those of children with nCAL (P < .05). Multivariate analysis showed that the increase of NT-proBNP and the decrease of Hb may be independent risk factors for the occurrence of CAL in children with KD. The clinical manifestation of children with IKD is not typical. Compared with KD children, the fever time is longer and the incidence of CAL is higher. Under-age, increased NT-proBNP and decreased Hb may be independent risk factors for CAL in KD children.

Tug-of-War between Covalent Binding and Electrostatic Interaction Effectively Killing E. coli without Detectable Resistance.

Antimicrobial resistance in Gram-negative bacteria has become one of the leading causes of morbidity and mortality and a serious worldwide public health concern due to the fact that Gram-negative bacteria have an additional outer membrane protecting them from an unwanted compound invading. It is still very difficult for antimicrobials to reach intracellular targets and very challenging to treat Gram-negative bacteria with the current strategies. Here, we found that (o-(bromomethyl)phenyl)boronic acid was incorporated into poly((2-N,N-diethyl)aminoethyl acrylate) (PDEA), forming a copolymer (poly(o-Bn-DEA)) having both phenylboronic acid (B) and ((2-N,N-diethyl)amino) (DEA) units. Poly(o-Bn-DEA) exhibits very strong intramolecular B-N coordination, which could highly promote the covalent binding of phenylboronic acid with lipopolysaccharide (LPS) on the outer membrane of E. coli and lodge poly(o-Bn-DEA) on the LPS layer on the surface of E. coli. Meanwhile, the strong electrostatic interaction between poly(o-Bn-DEA) and the negatively charged lipid preferred tugging the poly(o-Bn-DEA) into the lipid bilayer of E. coli. The combating interactions between covalent binding and electrostatic interaction form a tug-of-war action, which could trigger the lysis of the outer membrane, thereby killing Gram-negative E. coli effectively without detectable resistance.

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.

Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cells.

In a tumor, the abnormal cancer cell proliferation results in an insufficient O2 supply, and meanwhile cancer cells consume O2 very fast. The imbalance between a low oxygen supply and overwhelming oxygen consumption results in a low oxygen concentration in solid tumors. Therefore, in order to relieve hypoxia in tumors, it is necessary to not only sustainably generate O2, but also inhibit mitochondrial respiration simultaneously. Here, we found that a single Ti2C(OH)2 nanomaterial not only can sustainably generate O2 but also simultaneously highly inhibits mitochondrial respiration via binding phosphorylation proteins onto the surface in cancer cells. Ce6 was linked onto Ti2C(OH)2, forming Ti2C(OH)2-Ce6. Ti2C(OH)2-Ce6 could highly relieve hypoxia in tumors via the combination of sustainable O2 generation and respiration inhibition, produce enough 1O2 to kill cancer cells via PDT, and also effectively convert the absorbed light energy into thermal energy to kill cancer cell via PTT, thereby highly enhancing the cancer therapy.

Correction: Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cells.

Correction for 'Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cells' by Wei-Qiang Huang et al., Mater. Horiz., 2021, DOI: .

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study. / æ§æžé»„é¢—ç²’è¾ åŠ©æ²»ç–—å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜ç–—æ•ˆçš„çœŸå®žä¸–ç•Œç ”ç©¶.

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.

Epidemiological characteristics and clinical manifestations of pediatric patients with COVID-19 in China: A multicenter retrospective study.

Importance: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians. Objective: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China. Methods: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. Interpretation: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

IL-17 stimulates neutrophils to release S100A8/A9 to promote lung epithelial cell apoptosis in Mycoplasma pneumoniae-induced pneumonia in children.

Mycoplasma pneumoniae-induced pneumonia (MPP) is a common cause of community-acquired respiratory tract infections, increasing risk of morbidity and mortality, in children. However, diagnosing early-stage MPP is difficult owing to the lack of good diagnostic methods. Here, we examined the protein profile of bronchoalveolar lavage fluid (BALF) and found that S100A8/A9 was highly expressed. Enzyme-linked immunosorbent assays used to assess protein levels in serum samples indicated that S100A8/A9 concentrations were also increased in serum obtained from children with MPP, with no change in S100A8/A9 levels in children with viral or bacterial pneumonia. In vitro, S100A8/A9 treatment significantly increased apoptosis in a human alveolar basal epithelial cell line (A549 cells). Bioinformatics analyses indicated that up-regulated S100A8/A9 proteins participated in the interleukin (IL)-17 signaling pathway. The origin of the increased S100A8/A9 was investigated in A549 cells and in neutrophils obtained from children with MPP. Treatment of neutrophils, but not of A549 cells, with IL-17A released S100A8/A9 into the culture medium. In summary, we demonstrated that S100A8/A9, possibly released from neutrophils, is a new potential biomarker for the clinical diagnosis of children MPP and involved in the development of this disease through enhancing apoptosis of alveolar basal epithelial cells.

Comparison of Clinical Characteristics Among COVID-19 and Non-COVID-19 Pediatric Pneumonias: A Multicenter Cross-Sectional Study.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias. Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test. Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups. Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.