1H NMR-Based Metabolomics Reveals Refined-Huang-Lian-Jie-Du-Decoction (BBG) as a Potential Ischemic Stroke Treatment Drug With Efficacy and a Favorable Therapeutic Window

Huang-Lian-Jie-Du-Decoction (HLJDD) is a traditional Chinese medicine (TCM) used to treat ischemic stroke. However, the complexity of its chemical composition makes quality control difficult. Berberine, baicalin, and geniposide are the three main ingredients in HLJDD. Here, a formula of BBG comprised of berberine, baicalin, and geniposide, known as Refined-Huang-Lian-Jie-Du-Decoction, was investigated for its efficacy, therapeutic window, and mechanisms of action. BBG was assessed on two major types of ischemic stroke, cerebral ischemia-reperfusion (I/R) injury, and continuous ischemia injury, respectively. BBG showed efficacy comparable to HLJDD in the treatment of cerebral I/R injury within 5 h after injury initiation but did poorly in treating continuous ischemia injury. BBG exhibited neuroprotective effects on cerebral I/R injury by regaining the balance in energy metabolism, oxidative stress, amino acid metabolism, inflammation, and nucleic acid metabolism. These results suggested that BBG could be a good alternative to HLJDD, with high efficacy and a long therapeutic window, which shows great potential for drug development to treat stroke

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

BackgroundIt remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line.Materials and MethodsFrom March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test.ResultsBoth in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p < 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123–13.183 and 1.11–11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008).ConclusionSarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line

Identification and isolation of Genotype-I Japanese Encephalitis virus from encephalitis patients

Historically, Japanese Encephalitis virus (JEV) genotype III (GIII) has been responsible for human diseases. In recent years, JEV genotype I (GI) has been isolated from mosquitoes collected in numerous countries, but has not been isolated from patients with encephalitis. In this study, we report recovery of JEV GI live virus and identification of JEV GI RNA from cerebrospinal fluid (CSF) of encephalitis patients in JE endemic areas of China. Whole-genome sequencing and molecular phylogenetic analysis of the JEV isolate from the CSF samples was performed. The isolate in this study is highly similar to other JEV GI strains which isolated from mosquitoes at both the nucleotide and deduced amino acid levels. Phylogenetic analysis based on the genomic sequence showed that the isolate belongs to JEV GI, which is consistent with the phylogenetic analysis based on the pre-membrane (PrM) and Glycoprotein genes. As a conclusion, this is the first time to isolate JEV GI strain from CSF samples of encephalitis patients, so continuous survey and evaluate the infectivity and pathogenecity of JEV GI strains are necessary, especially for the JEV GI strains from encephalitis patients. With respect to the latter, because all current JEV vaccines (live and inactivated are derived from JEV GIII strains, future studies should be aimed at investigating and monitoring cross-protection of the human JEV GI isolates against widely used JEV vaccines

Clinical and radiological characteristics of pediatric COVID-19 before and after the Omicron outbreak: a multi-center study

IntroductionThe emergence of the Omicron variant has seen changes in the clinical and radiological presentations of COVID-19 in pediatric patients. We sought to compare these features between patients infected in the early phase of the pandemic and those during the Omicron outbreak.MethodsA retrospective study was conducted on 68 pediatric COVID-19 patients, of which 31 were infected with the original SARS-CoV-2 strain (original group) and 37 with the Omicron variant (Omicron group). Clinical symptoms and chest CT scans were examined to assess clinical characteristics, and the extent and severity of lung involvement.ResultsPediatric COVID-19 patients predominantly had normal or mild chest CT findings. The Omicron group demonstrated a significantly reduced CT severity score than the original group. Ground-glass opacities were the prevalent radiological findings in both sets. The Omicron group presented with fewer symptoms, had milder clinical manifestations, and recovered faster than the original group.DiscussionThe clinical and radiological characteristics of pediatric COVID-19 patients have evolved with the advent of the Omicron variant. For children displaying severe symptoms warranting CT examinations, it is crucial to weigh the implications of ionizing radiation and employ customized scanning protocols and protective measures. This research offers insights into the shifting disease spectrum, aiding in the effective diagnosis and treatment of pediatric COVID-19 patients

Research on Optimization of Aircraft Climb Trajectory considering Environmental Impact

Trajectory-based operation is a new technology that will be developed in the next generation of air traffic management. In order to clarify the optimization space of fuel consumption and emission impact on the environment under the specific operation limitation of air traffic management in the process of aircraft climb, an aircraft climb performance parameter optimization model considering the environmental impact is established. First, the horizontal and vertical climb models are established for the aircraft climb process, and then the optimization objectives are constructed by considering the impact of fuel consumption, exhaust emissions on air temperature, and the convenience of the flight process. Finally, the multiobjective model is solved by genetic algorithm. The B737-800 civil aviation aircraft is selected for simulation experiment to analyze the impact of speed change on the optimization target. The results show that with the change of speed, the fuel consumption and temperature rise are different, and the climb performance parameters of the aircraft are affected by the maximum RTA. By optimizing the flight parameters of the aircraft, it can effectively reduce the impact of flight on the environment and provide theoretical support for the sustainable development of civil aviation