Heavy metal induced ecophysiological function alterations in the euhalophyte Suaeda salsa

Heavy metal accumulation affects the physiological status of plants. Suaeda salsa L. is used to investigate the toxic effects of cadmium (Cd) and lead (Pb) either alone or mixtures under the static test conditions. Cd-Pb mixture exposure can decrease lignin content and weaken the increase. Mitochondrial calcium content significantly reduced at 30 µM Cd and Pb exposure. Cd-Pb mixture exposure can increase calcium content under the same concentration exposure. Soluble sugar levels noted a significant decrease in Cd, Pb and Cd-Pb mixture exposure. The accumulations of Cd, Pb in S. salsa were significantly increased with exposure time. Soluble protein (SP) in S. salsa at 30 µM concentration treatments decreased with exposure time. Heat shock protein 70 (HSP70) was enhanced lightly along with the increase of added Cd-Pb from 30 to 70 &3181;M and then decreased below the controls which present a synergistic effect. Heat shock protein 60 (HSP60) increased slightly with the increase of Cd-Pb from 30 to 110 µM, and then decreased hereafter and significantly inhibited at 150 ƒÊM (p<0.05). Moreover, Cd-Pb mixture exposure significantly increased the Rubisco activity under lower concentration and presented antagonistic effect. At the same time, the viability percent decreased as increase Cd-Pb concentration exposure (p0.05), it presents a dose-dependent manner. Mitochondrial cells treated with Cd-Pb exposure obviously reduced the reactive oxygen species (ROS) levels in mitochondrial cells.Key words: Suaeda salsa, heavy metal, ecophysiological function

Toxicological responses in alfalfa (Medicago sativa) under joint stress of cadmium and napropamide

Joint effects of Cd2+ and napropamide in seeds, roots or leaves of alfalfa were investigated under different treatments. It was shown that single stress of Cd2+ or napropamide decreased chlorophyll content after 30 days of treatment in different concentrations. The decrease in chlorophyll content became insignificant under joint stress of Cd2+ and napropamide. It can be concluded that the interaction of Cd2+ and napropamide would aggravate the toxic effects on chlorophyll synthesis in leaves of alfalfa. The joint effect of Cd2+ and napropamide was markedly significant (p < 0.05) on the change of SP content in leaves in all treatment. Moreover, Cd2+ and napropamide mixture exposure can increase lignin content and present synergistic effect. In a mixture treated with Cd2+ and napropamide, 52% decrease in β-carotene content contrasted with the control in young leaves. The contents of protein thiols and non-protein thiols in the roots of alfalfa were significantly increased by Cd2+ treatment in all treatment levels. In contrast, increasing napropamide supply did not have any significant effect on the protein thiols and non-protein thiols content. The Cd2+ induced accumulation of O2•- in seeds could be increased by treatment with different Cd2+ concentration. Production of H2O2 and O2•- was also higher in the napropamide treatments than in the control. The addition of napropamide significantly increased the H2O2 and O2•- level in the seeds of alfalfa.Key words: Alfalfa, joint stress, cadmium, napropamide

Prediction of acute kidney injury in patients with femoral neck fracture utilizing machine learning

BackgroundAcute kidney injury (AKI) is a common complication associated with significant morbidity and mortality in high-energy trauma patients. Given the poor efficacy of interventions after AKI development, it is important to predict AKI before its diagnosis. Therefore, this study aimed to develop models using machine learning algorithms to predict the risk of AKI in patients with femoral neck fractures.MethodsWe developed machine-learning models using the Medical Information Mart from Intensive Care (MIMIC)-IV database. AKI was predicted using 10 predictive models in three-time windows, 24, 48, and 72 h. Three optimal models were selected according to the accuracy and area under the receiver operating characteristic curve (AUROC), and the hyperparameters were adjusted using a random search algorithm. The Shapley additive explanation (SHAP) analysis was used to determine the impact and importance of each feature on the prediction. Compact models were developed using important features chosen based on their SHAP values and clinical availability. Finally, we evaluated the models using metrics such as accuracy, precision, AUROC, recall, F1 scores, and kappa values on the test set after hyperparameter tuning.ResultsA total of 1,596 patients in MIMIC-IV were included in the final cohort, and 402 (25%) patients developed AKI after surgery. The light gradient boosting machine (LightGBM) model showed the best overall performance for predicting AKI before 24, 48, and 72 h. AUROCs were 0.929, 0.862, and 0.904. The SHAP value was used to interpret the prediction models. Renal function markers and perioperative blood transfusions are the most critical features for predicting AKI. In compact models, LightGBM still performs the best. AUROCs were 0.930, 0.859, and 0.901.ConclusionsIn our analysis, we discovered that LightGBM had the best metrics among all algorithms used. Our study identified the LightGBM as a solid first-choice algorithm for early AKI prediction in patients after femoral neck fracture surgery

Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats Revealed by Anti-Inflammatory Assessments and NMR-Based Metabonomics

The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats

Anti-angiogenic therapy or immunotherapy? A real-world study of patients with advanced non-small cell lung cancer with EGFR/HER2 exon 20 insertion mutations

BackgroundFor patients with EGFR/HER2 exon20 insertions, platinum-containing double-drug chemotherapy is still the standard treatment method. First-generation TKIs have almost no therapeutic activity against EGFR exon 20 insertions. The efficacy of second-and third-generation TKIs is still controversial. Immunotherapy research is scarce, and there is an urgent need for more evidence and new treatment options for this group of patients.MethodsWe reviewed patients with advanced NSCLC with EGFR/HER2 exon 20 insertion mutations treated in Shanghai Chest Hospital and Shanghai Pulmonary Hospital from 2015 to 2022 and assessed the efficacy of receiving chemotherapy, anti-angiogenic therapy and immunotherapy, including objective response rate (ORR) and disease control rate (DCR), and compared progression-free survival (PFS) and overall survival (OS).ResultsOf the 126 patients included in the study, 51 patients had EGFR20ins mutations and 7 5 patients had HER2-20ins mutations. In the first-line treatment, bevacizumab + chemotherapy (Beva+Chemo), ICI+chemotherapy (ICI+Chemo), compared with chemotherapy alone (Chemo), ORR: 40% vs 33.3% vs 15% (p=0.0168); DCR: 84% vs 80.9% vs 67.5% (p=0.1817); median PFS: 8.3 vs 7.0 vs 4.6 months (p=0.0032), ICI+Chemo has a trend of benefiting on OS. Stratified analysis showed that compared with chemotherapy, ICI+Chemo was more effective for EGFR20ins mutation with median PFS: 10.3 vs. 6.3m (P=0.013); Beva+Chemo was more effective for HER2-20ins mutation, with a median PFS: 6.6 vs. 4.3m (p=0.030). In the second-line treatment of EGFR20ins mutation, bevacizumab + chemotherapy has a significant advantage in PFS compared with targeted therapy, median PFS:10.8 vs 4.0 months (P=0.016).ConclusionFor patients with EGFR20ins mutation, compared to chemotherapy, ICI+Chemo prolongs PFS, and after chemotherapy progression, bevacizumab combined with chemotherapy seems better than Furmonertinib-based targeted therapy on PFS. For HER2-20ins mutation, Beva+Chemo may be a better choice

Global Epidemiology of Dengue Outbreaks in 1990–2015: A Systematic Review and Meta-Analysis

Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted by Aedes mosquitoes. Approximately 50–100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term “dengue outbreak.” In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (both P < 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR = 1.65), suffering from hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53), respectively (all P < 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment