Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation.

BACKGROUND: Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. METHODS: Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5-24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. RESULTS: In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. CONCLUSIONS: Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Retrospective computed tomography assessment of chemotherapy-related pneumonia with severity screening in pediatric acute lymphoblastic leukemia by radiological imaging.

Objectives: To evaluate the radiological imaging-guided severity along the pneumonia course and evaluate the chest computed tomography (CT) findings of chemotherapy-related pneumonia in children with acute lymphoblastic leukemia (ALL). Materials and methods: A retrospective database review of children with ALL was conducted from March 2016 to August 2021 to identify cases with CT images who developed pneumonia during the chemotherapy course. A total of 51 children with ALL developed pneumonia were ultimately included (31 boys and 20 girls, mean age: 6 ± 4 years [standard deviation]). Each child's demographics, medical records, and laboratory results were collected. The CT images were then reviewed and the radiologic severity index (RSI) was calculated based on the regional opacity and implicated volume. A t-test, U test, Pearson's Chi-square test, and Fisher's exact test were performed to compare the clinical or radiologic features between the severe and moderate cases. The linear regression models were employed to analyze the correlation of RSIs with other clinical features. Results: Eleven children (22 %, 11/51) displayed severe phenotypes associated with respiratory failure. The ground glass opacity (GGO) frequently appeared (65 % of CT images). The baseline RSI was positively associated with the lowest lymphocyte (p = .003), neutrophil (p = .01) counts, and the highest C-reactive protein level (p = .04). The peak RSI may predict severe phenotypes at a cutoff of 4.5 (AUC 0.76 [0.61, 0.91]) with 73 % sensitivity and 63 % specificity. Conclusion: The chest CT images of children with chemotherapy-related pneumonia displayed clinically related baseline RSI and a peak RSI of >4.5 of 36 predicted severe phenotypes.

Design and Validation of a Novel Evaluation Scale to Predict Inpatient Large Vessel Occlusion Strokes: Clinical Assessment Stroke Severity for Inpatient Scale.

OBJECTIVES: A large quantity of ischemic stroke events occur in patients hospitalized for non-stroke-related reason. No scale has been developed to identify the large vessel occlusion (LVO) among inpatient stroke alerts. We aimed to develop a novel evaluation scale to predict LVO from in-hospital stroke alerts. METHODS: Data from consecutive in-hospital stroke alerts were analyzed at a single high volume stroke center between January 2016 and October 2020. We developed a predictive scale based on the first half of patients (training group) using multivariate logistic regression and evaluated it in the remaining half of patients (validation group) adopting receiver operating curve. Receiver operating characteristics of the scale were analyzed to evaluate its value for the detection of LVO. RESULTS: A total of 243 patients were enrolled for further study, among them, 94 (38.7%) had confirmed LVO. Three risk factors independently predicted the presence of LVO: recent cardiac or pulmonary procedure (1 point), neurological deficit scale (≥1: 2 points), and history of atrial fibrillation (1 point). The CAPS scale was generated based on predictive factors and demonstrated highly effective discrimination in identifying the presence of LVO in the training group (area under curve = 0.956) and the validation group (area under curve = 0.940). When the score ≥2, CAPS scale showed 97.9% sensitivity, 79.2% specificity, 74.8% positive predictive value, and 98.3% negative predictive value for discriminating LVO. CONCLUSIONS: CAPS scale was developed for identifying LVO among inpatient stroke alerts with high sensitivity and specificity, which may help to quickly prompt responses by appropriate stroke teams.

Initial assessment of treatment of talar posterior process fractures with open reduction and percutaneous fixation.

The purpose of this study was to provide an initial assessment of treatment for talar posterior process fractures using open reduction and internal fixation (ORIF) through posteromedial approach and percutaneous screw fixation. From January 2014 to December 2018, 12 cases with displaced fracture of talar posterior process were treated in our department. The clinical and radiological results were assessed after 4 and 12 months of operation with Visual Analog Scale (VAS) pain and American Orthopedic Foot and Ankle Society (AOFAS) scores. ORIF was performed in four of the cases and percutaneous screw fixation was performed in eight of the cases. The average follow-up period was 13 months. Complications such as wound infection, nerve injury, screw loosening, malunion or nonunion of fracture were absent. For clinical assessment, considerable mprovements were observed for the AOFAS and VAS scores at 4 and 12 months postoperatively for both techniques. There was no significant difference for AOFAS scores and VAS scores between the two techniques (p > 0.05). Both techniques showed good functional outcome and were performed for posterior talar process fracture following the fracture displacement guidelines. Percutaneous screw fixation treatment with computer-assisted three-dimensional evaluation shortened the operation time and reduced incidences of surgical complications.

[Research model on commodity specification standard of radix Chinese materia medica].

As an important part of the market commodity circulation, the standard grade of Chinese traditional medicine commodity is very important to restrict the market order and guarantee the quality of the medicinal material. The State Council issuing the "protection and development of Chinese herbal medicine (2015-2020)" also make clear that the important task of improving the circulation of Chinese herbal medicine industry norms and the commodity specification standard of common traditional Chinese medicinal materials. However, as a large class of Chinese herbal medicines, the standard grade of the radix is more confused in the market circulation, and lack of a more reasonable study model in the development of the standard. Thus, this paper summarizes the research background, present situation and problems, and several key points of the commodity specification and grade standard in radix herbs. Then, the research model is introduced as an example of Pseudostellariae Radix, so as to provide technical support and reference for formulating commodity specifications and grades standard in other radix traditional Chinese medicinal materials.

Epidemiological survey on newborns born at the obstetric departments in hospitals in mid-southern region of China in 2005.

OBJECTIVE: To investigate the situations at birth of newborns in the mid-southern region of China by performing a survey on the newborns born at urban hospitals. METHODS: A total of 23 hospitals in the mid-southern region of China were selected to participate in this survey. The data of 15,582 newborns who were born at the obstetric departments from January 1, 2005 to December 31, 2005 were retrospectively investigated. RESULTS: The male to female ratio among newborns was 1.16:1. The incidence of preterm birth was 8.11%, while very low birth weight (VLBW) infants accounted for 0.73%. The rates of spontaneous vaginal delivery and cesarean section ware 57.52% and 40.82%, respectively, while the other delivery modes accounted for 1.66%. The incidence of neonatal asphyxia was 3.78% (0.75% for heavy asphyxia). The mortality of newborns was 0.55% (5.56% for preterm infants). CONCLUSIONS: The incidences of preterm birth and neonatal asphyxia are relatively high in the mid-southern region of China. The rate of cesarean section is abnormally high, which is due mainly to social factors.