The protective effect of ginsenoside Rg1 against sepsis-induced lung injury through PI3K-Akt pathway: insights from molecular dynamics simulation and experimental validation.

Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation and protect lung epithelial cells against tissue damage. However, the specific roles and mechanisms by which GRg1 mitigates SALI have yet to be fully elucidated. In this context, we employed a relevant SALI mouse model, alongside network pharmacology, molecular docking, and molecular dynamics simulation to pinpoint GRg1's action targets, complemented by in vitro assays to explore the underlying mechanisms. Our research shows that GRg1 alleviates CLP-induced SALI, decreasing lung tissue damage and levels of serum proinflammatory factor IL-6, TNF-α, and IL-1ß, also enhancing the survival rate of CLP mice. A total of 116 common targets between GRg1 and ALI, with specific core targets including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, and ALB. Further in vitro experiments assessed GRg1's intervention effects on MLE-12 cells exposed to LPS, with qRT-PCR analysis and molecular dynamics simulations confirming AKT1 as the key target with the favorable binding activity for GRg1. Western blot results indicated that GRg1 increased the Bcl-2/Bax protein expression ratio to reduce apoptosis and decreased the high expression of cleaved caspase-3 in LPS-induced MLE-12 cells. More results showed significant increases in the phosphorylation of PI3K and AKT1. Flow cytometric analysis using PI and Annexin-V assays further verified that GRg1 decreased the apoptosis rate in LPS-stimulated MLE-12 cells (from 14.85 to 6.54%, p < 0.05). The employment of the AKT1 inhibitor LY294002 confirmed these trends, indicating that AKT1's inhibition negates GRg1's protective effects on LPS-stimulated MLE-12 cells. In conclusion, our research highlights GRg1's potential as an effective adjunct therapy for SALI, primarily by inhibiting apoptosis in alveolar epithelial cells and reducing pro-inflammatory cytokine secretion, thus significantly enhancing the survival rates of CLP mice. These beneficial effects are mediated through targeting AKT1 and activating the PI3K-AKT pathway.

Post-traumatic Stress Disorder Symptoms and Quality of Life of COVID-19 Survivors at 6-Month Follow-Up: A Cross-Sectional Observational Study.

Background: Post-traumatic stress disorder (PTSD) is the most common psychiatric sequelae among novel coronavirus disease (COVID-19) patients. The aim of this study was to determine the prevalence of PTSD symptoms, PTSD-related factors, and its relationship with quality of life at long-term follow-up in hospitalized COVID-19 survivors. Methods: A cross-sectional study was undertaken to evaluate the health consequences of hospitalized COVID-19 survivors. All participants were interviewed face-to-face through a series of questionnaires: a researcher-developed symptom questionnaire, the Post-traumatic Stress Disorder Checklist-Civilian Version, the Generalized Anxiety Disorder 7-item, and the 36-item Short Form. Results: A total of 574 participants were enrolled with an average age of 57 years. The median follow-up time post-discharge was 193.9 days (SD = 15.32). Among the participants, 77.9% of survivors presented with at least one symptom, where fatigue or muscle weakness (47.9%) was reported the most frequently, followed by chest distress (29.4%) and sleep difficulty (29.4%). The prevalence of PTSD was 11.15% [95% confidence interval (CI): 8.56, 13.73] with a cut-off score of 44. Factors such as respiratory symptoms [odds ratio (OR): 3.53; 95% CI: 1.68-7.42], anxiety (OR: 14.64; 95% CI: 7.09-30.21), and sleep difficulty (OR: 2.17; 95% CI: 1.14-4.16) were positively related to PTSD. Those COVID-19 survivors with potential PTSD had significantly lower quality of life than those without (P < 0.05). Conclusion: Our study illustrated that a significant number of COVID-19 survivors were suffering from physical or mental distress to varying degrees at 6 months post-discharge. People with PTSD were more likely to experience persistent respiratory symptoms and sleep difficulty, as well as anxiety and a decreased quality of life. Such survivors require greater attention to their mental health, particularly the PTSD symptoms at the early phase, which may play an important role in the recovery of both the physical and psychological health of COVID-19 survivors.

Prognostic values of SOFA score, qSOFA score, and LODS score for patients with sepsis.

BACKGROUND: Sepsis continues to carry a high rate of mortality, which makes effective and simple evaluation methods for predicting the prognosis of septic patients especially important. In this study, we retrospectively analyzed the relationships between three scoring systems including Sequential Organ Failure Assessment (SOFA) score, Quick SOFA (qSOFA) score, and Logistic Organ Dysfunction System (LODS) score and the prognoses of septic patients. METHODS: The baseline data, SOFA score, qSOFA score, LODS score, 28-day prognosis, and 90-day prognosis of patients who met the diagnostic criteria of sepsis were retrieved from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Receiver operating characteristic (ROC) curves were drawn for various indicators, and comparisons were drawn between the areas under the ROC curves (AUC) of the different scoring systems. RESULTS: The 28-day AUC was 0.661 (0.652, 0.670) for SOFA, 0.558 (0.548, 0.568) for qSOFA, and 0.668 (0.658, 0.677) for LODS; AUC-qSOFA vs. AUC-LODS was 0.103 (0.087, 0.120) (P<0.001), and AUC-qSOFA vs. AUC-LODS was 0.110 (0.094, 0.125) (P<0.001). The 90-day AUC was 0.630 (0.621, 0.640) for SOFA, 0.551 (0.541, 0.560) for qSOFA, and 0.644 (0.635, 0.653) for LODS; AUC-SOFA vs. AUC-qSOFA was 0.079 (0.065, 0.094) (P<0.001), and AUC-qSOFA vs. AUC-LODS was 0.093 (0.079, 0.107) (P<0.001). CONCLUSIONS: SOFA score, qSOFA score, and LODS score can all be used to predict the prognosis of septic patients. LODS score and SOFA score have higher accuracy than qSOFA score; however, qSOFA is simpler to use, making it a more suitable tool in an emergency setting.

Efficacy and safety of Shenfu injection for patients with return of spontaneous circulation after sudden cardiac arrest: Protocol for a systematic review and meta-analysis.

BACKGROUND: Sudden cardiac arrest (SCA) is one of the most common critical illnesses encountered in clinical practice. Shenfu injection (SFI) has received extensive attention as an alternative therapy that can effectively maintain the autonomic circulation function after cardiopulmonary resuscitation. However, the mechanism of SFI is not yet fully understood. In addition, there has been no systematic review or meta-analysis of SFI in the treatment of patients with return of spontaneous circulation after SCA. Herein, we describe the protocol of a proposed study based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that aims to systematically evaluate the efficacy and safety of SFI in patients with return of spontaneous circulation after SCA. METHODS: Two researchers will search 9 electronic databases (PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese VIP Information, Wanfang, and Chinese Biomedical Database) to identify all studies that meet the inclusion criteria and were published before July 2018. After information extraction and methodological quality evaluation, we will use Stata 13.0 software (STATA Corporation, College Station, TX, USA) to synthesize the data. The primary outcomes will be the survival rate and Glasgow Coma Scale. RESULTS: The data synthesis results will objectively illustrate the efficacy and safety of SFI in patients with return of spontaneous circulation after SCA. CONCLUSION: The findings will provide a reference for the use of SFI in the treatment of patients with return of spontaneous circulation after SCA. REGISTRATION: PROSPERO (registration number: CRD42018104230).

Adult onset Still's disease accompanied by acute respiratory distress syndrome: A case report.

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fever and arthralgia/arthritis. The most common pulmonary manifestations associated with AOSD are pulmonary infiltrates and pleural effusion. The present study describes a 40-year-old male with AOSD who developed fever, sore throat and shortness of breath. Difficulty breathing promptly developed, and the patient was diagnosed with acute respiratory distress syndrome (ARDS). The patient did not respond to antibiotics, including imipenem, vancomycin, fluconazole, moxifloxacin, penicillin, doxycycline and meropenem, but was sensitive to glucocorticoid treatment, including methylprednisolone sodium succinate. ARDS accompanied by AOSD has been rarely reported in the literature. In conclusion, in a patient with ARDS who does not respond to antibiotic treatment, the involvement of AOSD should be considered.