Antioxidant and anti-inflammatory function of Eupatorium adenophora Spreng leaves (EASL) on human intestinal Caco-2 cells treated with tert-butyl hydroperoxide.

Chronic non-communicable diseases (CNCDs) pose a significant public health challenge. Addressing this issue, there has been a notable breakthrough in the prevention and mitigation of NCDs through the use of antioxidants and anti-inflammatory agents. In this study, we aim to explore the effectiveness of Eupatorium adenophora Spreng leaves (EASL) as an antioxidant and anti-inflammatory agent, and its potential applications. To construct a cellular model of oxidative damage and inflammation, Caco-2 cells were treated with tert-butyl hydroperoxide (t-BHP). The biocompatibility of EASL-AE with Caco-2 cells was assessed using the MTT assay, while compatibility was further verified by measuring LDH release and the protective effect against oxidative damage was also assessed using the MTT assay. Additionally, we measured intracellular oxidative stress indicators such as ROS and 8-OHdG, as well as inflammatory pathway signalling protein NFκB and inflammatory factors TNF-α and IL-1ß using ELISA, to evaluate the antioxidant and anti-inflammatory capacity of EASL-AE. The scavenging capacity of EASL-AE against free radicals was determined through the DPPH Assay and ABTS Assay. Furthermore, we measured the total phenolic, total flavonoid, and total polysaccharide contents using common chemical methods. The chemical composition of EASL-AE was analyzed using the LC-MS/MS technique. Our findings demonstrate that EASL-AE is biocompatible with Caco-2 cells and non-toxic at experimental levels. Moreover, EASL-AE exhibits a significant protective effect on Caco-2 cells subjected to oxidative damage. The antioxidant effect of EASL-AE involves the scavenging of intracellular ROS, while its anti-inflammatory effect is achieved by down-regulation of the NFκB pathway. Which in turn reduces the release of inflammatory factors TNF-α and IL-1ß. Through LC-MS/MS analysis, we identified 222 compounds in EASL-AE, among which gentianic acid, procaine and L-tyrosine were the compounds with high antioxidant capacity and may be the effective constituent for EASL-AE with antioxidant activity. These results suggest that EASL-AE is a natural and high-quality antioxidant and anti-inflammatory biomaterial that warrants further investigation. It holds great potential for applications in healthcare and other related fields.

Blueberry anthocyanin based active intelligent wheat gluten protein films: Preparation, characterization, and applications for shrimp freshness monitoring.

The aim of this study was to prepare active intelligent gluten protein films using wheat gluten protein (WG) and apple pectin (AP) as film-forming matrices, and blueberry anthocyanin extract (BAE) as a natural indicator. SEM and FT-IR analyses demonstrated the successful immobilization of BAE in the film matrix by hydrogen bonding interactions and its compatibility with WG and AP. The resultant WG-AP/BAE indicator films demonstrated notable antioxidant activity, color stability, barrier qualities, pH and ammonia response sensitivity, and mechanical properties. Among them, WG-AP/BAE5 exhibited the best mechanical properties (TS: 0.83 MPa and EB: 242.23%) as well as the lowest WVP (3.92 × 10-8 g.m/m2.Pa.s), and displayed high sensitivity to volatile ammonia. In addition, WG-AP/BAE5 showed a color shift from purplish red to green to yellowish green, demonstrating the monitoring of shrimp freshness in real time. Consequently, this study offers a firm scientific foundation for the development of active intelligent gluten protein films and their use in food freshness assessments.

Uncovering the characteristics of the gut microbiota in patients with ischemic stroke and hemorrhagic stroke.

This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case-control study was conducted, and high-throughput sequencing of the V4-V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.

Association Between Dietary Factors and Chronic Sinusitis Among Korean Individuals: Insights From a Large Population-Based Study in Asia.

Objective: Population-based studies on chronic sinusitis have predominantly focused on Europe and the Americas, but research on chronic sinusitis within large Asian populations remains scarce. This study aims to explore the link between dietary factors and chronic sinusitis among ethnic Koreans in Asia. Design: A cross-sectional study. Setting: Data were collected from the Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. Participants: Participants in the study were included based on a doctor's diagnosis of chronic sinusitis, as determined through the ear, nose, and throat examination questionnaires. Results: Adolescents [adjusted P value (aP) < .001, adjusted odds ratio (aOR) = 1.881, 95% confidence interval (CI) = 1.380-2.564] and individuals with college and higher education (aP = .042, aOR = 1.298, 95% CI = 1.009-1.669) were more likely to develop chronic rhinosinusitis. In addition, levels of dietary fat [P = .001, interquartile range (IQR) = 34.085] and energy intake (P = .004, IQR = 981.106) were associated with an increased risk of chronic sinusitis. Moreover, high dietary inflammatory index (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721), and high intake of fried pork chops (aP = .028, aOR = 1.335, 95% CI = 1.033-1.777), bread (aP = .024, aOR = 1.364, 95% CI = 1.042-1.786), and rice (aP = .021, aOR = 1.382, 95% CI = 1.051-1.818) were risk factors for chronic sinusitis, while cucumber consumption (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721) was a protective factor for chronic sinusitis. Conclusion: This study revealed a significant correlation between diet and development of chronic sinusitis. These findings suggest that promoting an anti-inflammatory dietary pattern and providing guidance on healthy eating habits could help reduce the incidence of chronic sinusitis and enhance its management.

Implementing a Barcode-Based Whole-Life Cycle Management Process to Improve Robotic Instrument Tracking.

Minimally invasive surgery can involve the use of robotics to improve patient outcomes. Some robotic systems require special instruments with a designated number of uses. In China, during the reprocessing of the robotic instruments, health care personnel determined that the existing tracking processes were inadequate. They conducted a quality improvement project with the goal of establishing a barcode-based standardized process for tracking robotic instruments. They implemented technology that generated a unique identifier each time a robotic instrument was reprocessed after use. Nurses scanned the identifier when surgeons used the instrument. The findings included the increased accuracy of use documentation and decreases in untraceable sterilization and use records, charging concerns, and average daily and monthly inventory times. An increase in adverse event reports associated with robotic instruments also was noted. The use of barcode technology for robotic instrument tracking continues at the facility and may be expanded for additional specialty instruments.

Current advances and future directions in combined hepatocellular and cholangiocarcinoma.

The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.

N-acetyl-l-methionine dietary supplementation improves meat quality by oxidative stability of finishing Angus heifers.

Methionine plays a vital role in protein synthesis, and regulation of antioxidant response in ruminants. This study aimed to assess the effects of dietary supplementation with N-acetyl-l-methionine (NALM), which serves a source of rumen-protected methionine, on growth performance, carcass traits, meat quality, and oxidative stability. Sixty Angus heifers (initial body weight = 408 ± 51.2 kg, 15-18 months) were stratified by body weight and randomly assigned to four dietary treatments: a control group (0% NALM), and experimental groups receiving diets containing 0.125%, 0.25%, and 0.50% NALM (dry matter (DM) basis), respectively. The experiment included a 2-week adaptation and a 22-week data and sample collection period. Results indicated that blood urea nitrogen in the plasma of the 0.25% NALM group was lower compared to the control and the 0.50% NALM groups (P = 0.02). The plasma methionine (P = 0.04), proline (P < 0.01), and tryptophan (P = 0.05) were higher in the 0.25% and 0.50% NALM groups, as well as the methionine and proline in the muscle of the 0.25% NALM group (P < 0.01). The muscle pH (P < 0.01) was increased by supplementing 0.25% and 0.50% NALM in diets but decreased the lactate (P < 0.01). The 0.25% NALM group also increased a* (P = 0.05), decreased L* (P = 0.05), drip loss (P = 0.01), and glycolytic potential in the muscle (P < 0.01). The total antioxidant capacity, superoxide dismutase, glutathione peroxidase, catalase, and glutathione in muscle of 0.25% NALM group were higher than that of the control (P < 0.01), and the malondialdehyde and protein carbonyl were lower (P < 0.01). In conclusion, the dietary supplement with NALM improves meat quality by enhancing the antioxidant effect of lipids and proteins.

Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis.

Pathogens detected by metagenomic next-generation sequencing (mNGS) and the laboratory blood culture flask method were compared to understand the advantages and clinical significance of mNGS assays in the etiological diagnosis of peritoneal dialysis-associated peritonitis (PDAP). The study involved a total of 37 patients from the hospital's peritoneal dialysis centre, six of whom were patients with non-peritoneal dialysis-associated peritonitis. Peritoneal dialysis samples were collected from the 37 patients, who were divided into two groups. One group's samples were cultured using conventional blood culture flasks, and the other samples underwent pathogen testing using mNGS. The results showed that the positive rate of mNGS was 96.77%, while that of the blood culture flask method was 70.97% (p < 0.05). A total of 29 pathogens were detected by mNGS, namely 24 bacteria, one fungus, and four viruses. A total of 10 pathogens were detected using the bacterial blood culture method, namely nine bacteria and one fungus. The final judgment of the PDAP's causative pathogenic microorganism was made by combining the clinical condition, response to therapy, and the whole-genome sequencing findings. For mNGS, the sensitivity was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77%, and the negative predictive value was 83.33%. For the blood culture flask method, the sensitivity was 70.97%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 0%. In conclusion, mNGS had a shorter detection time for diagnosing peritoneal dialysis-related peritonitis pathogens, with a higher positive rate than traditional bacterial cultures, providing significant advantages in diagnosing rare pathogens.

Bayesian analysis of joint quantile regression for multi-response longitudinal data with application to primary biliary cirrhosis sequential cohort study.

This article proposes a Bayesian approach for jointly estimating marginal conditional quantiles of multi-response longitudinal data with multivariate mixed effects model. The multivariate asymmetric Laplace distribution is employed to construct the working likelihood of the considered model. Penalization priors on regression parameters are incorporated into the working likelihood to conduct Bayesian high-dimensional inference. Markov chain Monte Carlo algorithm is used to obtain the fully conditional posterior distributions of all parameters and latent variables. Monte Carlo simulations are conducted to evaluate the sample performance of the proposed joint quantile regression approach. Finally, we analyze a longitudinal medical dataset of the primary biliary cirrhosis sequential cohort study to illustrate the real application of the proposed modeling method.

Parent material influences soil properties to shape bacterial community assembly processes, diversity, and enzyme-related functions.

Soil parent material is the second most influential factor in pedogenesis, influencing soil properties and microbial communities. Different assembly processes shape diverse functional microbial communities. The question remains unresolved regarding how these ecological assembly processes affect microbial communities and soil functionality within soils on different parent materials. We collected soil samples developed from typical parent materials, including basalt, granite, metamorphic rock, and marine sediments across soil profiles at depths of 0-20, 20-40, 40-80, and 80-100 cm, within rubber plantations on Hainan Island, China. We determined bacterial community characteristics, community assembly processes, and soil enzyme-related functions using 16S rRNA high-throughput sequencing and enzyme activity analyses. We found homogeneous selection, dispersal limitation, and drift processes were the dominant drivers of bacterial community assembly across soils on different parent materials. In soils on basalt, lower pH and higher moisture triggered a homogeneous selection-dominated assembly process, leading to a less diverse community but otherwise higher carbon and nitrogen cycling enzyme activities. As deterministic process decreased, bacterial community diversity increased with stochastic process. In soils on marine sediments, lower water, carbon, and nutrient content limited the dispersal of bacterial communities, resulting in higher community diversity and an increased capacity to utilize relative recalcitrant substrates by releasing more oxidases. The r-strategy Bacteroidetes and genera Sphingomonas, Bacillus, Vibrionimonas, Ochrobactrum positively correlated with enzyme-related function, whereas k-strategy Acidobacteria, Verrucomicrobia and genera Acidothermus, Burkholderia-Caballeronia-Paraburkholderia, HSB OF53-F07 showed negative correlations. Our study suggests that parent material could influence bacterial community assembly processes, diversity, and soil enzyme-related functions via soil properties.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Structurally diverse phthalides from fibrous roots of Ligusticum chuanxiong Hort. and their biological activities.

Falonolide A (1) and B (2), two novel polyyne hybrid phthalides resulting from unprecedented carbon skeleton polymerized by Z-ligustilide and falcarindiol, along with six new related phthalides (3-8), were isolated from Ligusticum chuanxiong Hort. Their structures were elucidated by spectroscopic analysis, computer-assisted structure elucidation (CASE) analysis, DP4+ probability analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1-8 was proposed, and the production mechanism of 2 was revealed by density functional theory (DFT) method. Compounds 4 and 6 exhibited significant vasodilatory activity with EC50 of 8.00 ± 0.86 and 6.92 ± 1.02 µM, respectively. Compound 4 also displayed significant inhibitory effect of NO production with EC50 value of 8.82 ± 0.30 µM. Based on the established compounds library, structure-activity relationship analysis of phthalides was explored to provide insights into the drug development of vasodilators and anti-flammatory.

Gut Microbiota Metabolite TMA May Mediate the Effects of TMAO on Glucose and Lipid Metabolism in C57BL/6J Mice.

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.

Rainfall-runoff partitioning in small watersheds of different vegetation types in the loess area based on hydrogen and oxygen isotope tracing.

Recognizing watershed runoff process and its component sources is a prerequisite for the rational use of water resources. To elucidate the effects and quantitative contributions of various vegetation types on the components of watershed runoff, we centered on the Caijiachuan main channel watershed in Jixian, Shanxi and five sub-watersheds with distinct vegetation types. By tracking the hydrological responses to two representative rainfall events and assessing the spatiotemporal variations in hydrogen and oxygen isotope signatures, we aimed to discern disparities in the runoff processes across these sub-watersheds and pinpoint their constituent origins. The results showed that under medium rainfall condition, the contribution rates of event water to the river flow of each watershed were in an order of protected forest (94.3%) > Caijiachuan main channel (83.1%) > agro-pastoral composite (64.3%) > plantation-secondary forest (52.4%) > cropland (0.3%) > secondary forest (0.0%); under light rainfall condition, plantation-secondary forest (52.4%) > protected forest (58.5%) > cropland (40.6%) > secondary forest (15.8%) > agro-pastoral composite (12.5%) > Caijiachuan main channel (9.3%). The event water contribution rate of secondary forest and protected forest watersheds to runoff was higher than that of plantation watersheds. The secondary forests watersheds had a stronger runoff storage capacity. The event water contribution rate of protected forest and agro-pastoral composite watersheds under medium rainfall intensity condition was greater than that under light rainfall intensity condition, while the event water contribution rate of cropland, plantation-secondary forest, and secondary forest watersheds was in adverse. The event water contribution to the runoff of forested watersheds was greater than that of cropland watersheds, which may be related to the presence of silt dams at the mouth of agricultural watershed channels. This study can provide a scientific basis for the analysis of water conservation and runoff change attribution in the loess area of west Shanxi.

Activation of free fatty acid receptors, FFAR1 and FFAR4, ameliorates ulcerative colitis by promote fatty acid metabolism and mediate macrophage polarization.

OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization. METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry. RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments. CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization.

Brain mechanism of acupuncture for children with anisometropic amblyopia: a resting functional magnetic resonance imaging study based on voxel-mirrored homotopic connectivity.

AIM: To explore the brain mechanism of acupuncture for children with anisometropic amblyopia using the voxel-mirror homotopic connectivity (VMHC) analysis method of resting functional magnetic resonance imaging (rs-fMRI) technology based on clinical effectiveness. METHODS: Eighty children with anisometropic monocular amblyopia were randomly divided into two groups: control (40 cases, 1 case of shedding) and acupuncture (40 cases, 1 case of shedding) groups. The control group was treated with glasses, red flash, grating, and visual stimulations, with each procedure conducted for 5min per time. Based on routine treatment, the acupuncture group underwent acupuncture of "regulating qi and unblocking meridians to bright eyes", Jingming (BL1), Cuanzhu (BL2), Guangming (GB37), Fengchi (GB20) acupoints were taken on both sides, with the needle kept for 30min each time. Both groups were treated once every other day, three times per week, for a total of 4wk. After the treatment, the overall curative effect of the two groups and the latency and amplitude changes of P100 wave of pattern visual-evoked potential were counted. At the same time, nine children with left eye amblyopia were randomly selected from the two groups and were scanned with rs-fMRI before and after treatment. The differences in the brain regions between the two groups were compared and analyzed with VMHC. RESULTS: Chi-square test showed a notable difference in the total efficiency rate between the acupuncture (94.87%) and control groups (79.49%). Regarding the P100 wave latency and amplitude, the acupuncture group had significantly shorter latency and higher amplitude of P100 wave than the control group. Moreover, the VMHC values of the bilateral temporal lobe, superior temporal gyrus, and middle temporal gyrus were notably increased in the acupuncture group after treatment. CONCLUSION: Acupuncture combined with conventional treatment can significantly improve the corrected visual acuity and optic nerve conduction in children with anisometropic amblyopia. Compared with the conventional treatment, the regulation of acupuncture on the functional activities of the relevant brain areas in the anterior cerebellum may be an effective acupuncture mechanism for anisometropic amblyopia.

Clozapine-Induced Severe Toxicity: Exploring the Pharmacokinetic Profile of Clozapine and Its Significance in Hemodynamic Instability - A Case Report.

Hemodynamic instability in patients with clozapine intoxication can indirectly reflect the serum concentration of clozapine.We have described a case of a 32-year-old pregnant woman who developed life-threatening clozapine toxicity at 28 weeks of gestation. The levels of clozapine and norclozapine in the serum were high. We initiated hemoperfusion(HP) and other detoxification therapies to remove the drug. The patient had severely dilated peripheral blood vessels, which led to cardiac symptoms such as fatal hypotension and uncontrollable tachycardia, resulting in very high cardiac output and elevated Central venous oxygen saturation (ScvO2). Pharmacological intervention significantly improved the hemodynamics.In light of our observations in the ongoing case, we posit that evaluating hemodynamic parameters before and after blood detoxification could serve as a valuable means to gauge effectiveness and provide guidance for treatment.

Predicting malnutrition in gastric cancer patients using computed tomography(CT) deep learning features and clinical data.

OBJECTIVE: The aim of this study is using clinical factors and non-enhanced computed tomography (CT) deep features of the psoas muscles at third lumbar vertebral (L3) level to construct a model to predict malnutrition in gastric cancer before surgery, and to provide a new nutritional status assessment and survival assessment tool for gastric cancer patients. METHODS: A retrospective analysis of 312 patients of gastric cancer were divided into malnutrition group and normal group based on Nutrition Risk Screening 2002(NRS-2002). 312 regions of interest (ROI) of the psoas muscles at L3 level of non-enhanced CT were delineated. Deep learning (DL) features were extracted from the ROI using a deep migration model and were screened by principal component analysis (PCA) and least-squares operator (LASSO). The clinical predictors included Body Mass Index (BMI), lymphocyte and albumin. Both deep learning model (including deep learning features) and mixed model (including selected deep learning features and selected clinical predictors) were constructed by 11 classifiers. The model was evaluated and selected by calculating receiver operating characteristic (ROC), area under curve (AUC), accuracy, sensitivity and specificity, calibration curve and decision curve analysis (DCA). The Cohen's Kappa coefficient (κ) was using to compare the diagnostic agreement for malnutrition between the mixed model and the GLIM in gastric cancer patients. RESULT: The results of logistics multivariate analysis showed that BMI [OR = 0.569 (95% CI 0.491-0.660)], lymphocyte [OR = 0.638 (95% CI 0.408-0.998)], and albumin [OR = 0.924 (95% CI 0.859-0.994)] were clinically independent malnutrition of gastric cancer predictor(P < 0.05). Among the 11 classifiers, the Multilayer Perceptron (MLP)were selected as the best classifier. The AUC of the training and test sets for deep learning model were 0.806 (95% CI 0.7485-0.8635) and 0.769 (95% CI 0.673-0.863) and with accuracies were 0.734 and 0.766, respectively. The AUC of the training and test sets for the mixed model were 0.909 (95% CI 0.869-0.948) and 0.857 (95% CI 0.782-0.931) and with accuracies of 0.845 and 0.861, respectively. The DCA confirmed the clinical benefit of the both models. The Cohen's Kappa coefficient (κ) was 0.647 (P < 0.001). Diagnostic agreement for malnutrition between the mixed model and GLIM criteria was good. The mixed model was used to calculate the predicted probability of malnutrition in gastric cancer patients, which was divided into high-risk and low-risk groups by median, and the survival analysis showed that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P = 0.005). CONCLUSION: Deep learning based on mixed model may be a potential tool for predicting malnutrition in gastric cancer patients.

Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

Preparation of pH-responsive polyurethane nano micelles and their antibacterial application.

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles' particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.