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Non-starch polysaccharides are major bioactive components in chestnuts, and can serve as water-soluble polysaccharides with potential prebiotic properties. This study aims to establish an in vitro digestion and fermentation model to reveal the digestive and fermentative characteristics of Non-starch polysaccharides from chestnut kernels (NSPCK). The results indicated that under simulated digestion, NSPCK was partially digested in gastric juice but remained significantly undigested in saliva and intestinal juice, demonstrating considerable resilience against hydrolysis. After digestion, NSPCK still exhibited stable rough, lamellar, and porous structure and maintained strong antioxidant capacity. Animal experiments revealed positive effects of NSPCK on blood lipid level, and colon tissue of mice. Moreover, NSPCK enhanced the accumulation of short-chain fatty acids during fermentation, particularly acetic acid, propionic acid, and butyric acid. Furthermore, NSPCK intervention increased the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, and at the same time reduced that of harmful bacteria such as Enterococcus.

ObjectiveTo establish a predictive model of aggressive behaviors from hospitalized patients with schizophrenia through applying multiple machine learning algorithms, to provide a reference for accurately predicting and preventing of the occurrence of aggressive behaviors.MethodsThe cluster sampling method was used to select patients with schizophrenia who were hospitalized in our hospital from July 2019 to August 2021 as the survey objects, and they were divided into an aggressive behavior group (611 cases) and a non-aggressive behavior group (1,426 cases) according to whether they experienced obvious aggressive behaviors during hospitalization. Self-administered General Condition Questionnaire, Insight and Treatment Attitude Questionnaire (ITAQ), Family APGAR (Adaptation, Partnership, Growth, Affection, Resolve) Questionnaire (APGAR), Social Support Rating Scale Questionnaire (SSRS) and Family Burden Scale of Disease Questionnaire (FBS) were used for the survey. The Multi-layer Perceptron, Lasso, Support Vector Machine and Random Forest algorithms were used to build a predictive model for the occurrence of aggressive behaviors from hospitalized patients with schizophrenia and to evaluate its predictive effect. Nomogram was used to build a clinical application tool.ResultsThe area under the receiver operating characteristic curve (AUC) values of the Multi-Layer Perceptron, Lasso, Support Vector Machine, and Random Forest were 0.904 (95% CI: 0.877–0.926), 0.901 (95% CI: 0.874–0.923), 0.902 (95% CI: 0.876–0.924), and 0.955 (95% CI: 0.935–0.970), where the AUCs of the Random Forest and the remaining three models were statistically different (p 0.5).ConclusionMachine learning models can fairly predict aggressive behaviors in hospitalized patients with schizophrenia, among which Random Forest has the best predictive effect and has some value in clinical application.

In this study, IDF from Pyrus ussuriensis Maxim pomace (PUIDF) was prepared, and its routine constituents as well as physicochemical properties and structure were analyzed. Moreover, the effect of PUIDF on obesity and gut microbiota (GM) through a high-fat diet (HFD) mouse model was investigated. The results demonstrated that PUIDF had a loose and porous surface structure and typical cellulose polysaccharide functional groups with good water holding, oil holding and swelling capacity, as well as glucose and cholesterol adsorption performance in vitro. PUIDF could significantly reduce weight gain and lipid and cholesterol levels in HFD-induced obese mice. More importantly, PUIDF intervention greatly improved the diversity of GM in mice, as well as regulated intestinal microbiota composition and increasing the abundance of short-chain fatty acid producing bacteria. These results suggest that PUIDF may have a positive effect to alleviate hyperlipidemia and improve intestinal bacterial ecosystems.

Castanea mollissima Blume has been used to treat a variety of diseases in Chinese traditional medicine. This study was aimed to examine the anti-fatigue effect of purified Chestnut flower flavonoids (CFF) in mice and its underlying mechanisms using the weight-loaded swimming test. The study revealed that the content of total flavonoids in CFF was 754.20 mgRE/gdm, which identified six main types of flavonoids, myricetin-3-O-glucoside, quercetin-3-O-rutinoside, quercetin-O-glucoside, kaempherol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, kaempferol, respectively. CFF showed excellent free radical scavenging and anti-fatigue effect. Notably, CFF significantly prolonged the swimming time of mice, while down-regulating the levels of lactate dehydrogenase (LDH), blood lactic acid (BLA), blood urea nitrogen (BUN), and creatine kinase (CK), and increasing liver and muscle glycogen. Meanwhile, CFF suppressed exercise-elicited oxidative stress through promoting the SOD activity and reducing the MDA level. Furthermore, CFF up-regulated PGC-1α and PPARα expression in mouse skeletal muscle. In conclusion, these findings indicate that CFF exerts an anti-fatigue effect presumably via energy reserves and oxidative stress inhibition.

Objective: Alcohol use disorder (AUD) is a serious issue worldwide and frequently co-occurs with depression. However, the quality of life (QOL) of AUD patients with and without depression is not well studied in the Chinese Han population. The aim of this study was to investigate QOL and its correlates in AUD patients with and without depression in China.Methods: Five hundred and fifteen psychiatric patients diagnosed with AUD were recruited. All these patients completed the Beck Depression Inventory (BDI) to assess depression, the Medical Outcome Study 36-Item Short Form Health Survey (SF-36) to evaluate QOL and the Alcohol Use Disorders Identification Test (AUDIT) to measure the severity of drinking.Results: Compared with AUD patients without depression, those with depression had a lower QOL in all eight domains of the SF-36 (all P < 0.001), but were more willing to have alcohol-related treatment (P < 0.05). Negative correlations were noted between (i) the BDI total score and all eight domains of the SF-36 (all P < 0.001); and (ii) between the AUDIT total score and six domains of the SF-36 (all P < 0.05).Conclusions: Depression impairs QOL in patients with AUD in China. Early intervention in comorbid depression to improve QOL is needed.

BackgroundDepressive symptoms are common among psychiatric patients with alcohol dependence (AD). However, the prevalence and clinical correlates of comorbid depressive symptoms are less well studied in Chinese Han patients.MethodsIn this hospital-based survey, we recruited 378 psychiatric patients diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). All patients completed the Beck Depression Inventory (BDI) to evaluate depressive symptoms and the Alcohol Use Disorders Identification Test (AUDIT) to assess the severity of drinking.ResultsCompared to patients without depressive symptoms, 48.9% (185/378) of the patients with comorbid depressive symptoms were younger, had a more unstable marital status, had a higher AUDIT total score, and had a higher adverse consequences subscore (all P < 0.05). Further logistic regression analysis showed that unstable marital status (Odds ratios [OR] = 2.20, 95% confidence interval [CI] 1.21–3.99) and AUDIT total score (OR=1.07, 95% CI 1.03–1.11) were significantly associated with depressive symptoms.ConclusionsOur findings indicate high comorbidity between AD and depressive symptoms in Chinese psychiatric patients. Moreover, some variables are correlates of comorbid depressive symptoms. Particular attention should be paid to the early detection and intervention for this comorbid condition and its risk factors.

Toll-like receptors (TLRs) are a group of highly conserved molecules which initiate the innate immune response to pathogens by recognizing structural motifs of microbes. Understanding the changes in chicken Toll-like receptors (ChTLRs) and signal adaptors expression that occur with Eimeria tenella infection will help to elucidate the molecular basis of immune control of coccidiosis caused by Eimeria. The present study detected the dynamic changes in the expression of ChTLRs and associated signal adaptors in the spleen and cecum of E. tenella-infected chickens during the early stage of infection. The results showed that the expression peak for ChTLRs, MyD88 and TRIF occurred at 12 h post-infection (hpi), ChTLR3, ChTLR15 and MyD88 mRNA expression in the spleen of E. tenella infected chickens were significantly higher (P

Objectives: Pulmonary metastasectomy (PM) for colorectal cancer may provide respite from systemic therapy and prolonged disease-free intervals. We sought to identify factors associated with PM and to characterize the differential impact on overall survival for those offered lung resection., Methods: The National Cancer Database was queried for stage IV colorectal cancer patients with lung-limited metastatic disease between 2010 and 2016. Among patients who underwent primary tumor resection, those who underwent PM were compared with those who did not. Penalized regression with the least absolute selection and shrinkage operator was used to determine factors associated with receiving metastasectomy as well as overall survival., Results: In total, 867 (15.1%) patients underwent resection of both primary tumor and pulmonary metastases whereas 4864 (84.8%) had primary tumor resection alone. In unadjusted analyses, metastasectomy patents were younger, more often privately insured, more educated, and traveled farther to receive care (all P < .001). In multivariable analyses, younger age, traveling >25 miles, and care at high-volume hospitals were associated with PM (P < .01). In addition, primary site surgery without PM was associated with worse overall survival (hazard ratio, 1.35; confidence interval, 1.23-1.49), even after adjusting for patient, tumor, and hospital-related factors., Conclusions: Patients who were older, who received care closer to home, and who were treated at low-volume hospitals were less likely to receive metastasectomy for lung-limited colorectal cancer after definitive resection of their primary tumor. Failure to receive PM resulted in worse overall survival, emphasizing the strong need for efforts to provide uniform, equitable care to all patients., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach also revealed expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of using transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to the identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling., Significance: The development of an approach to interrogate molecular subtypes, cancer-associated pathways, and differentially expressed genes through RNA sequencing of plasma extracellular vesicles lays the foundation for liquid biopsy-based longitudinal monitoring of patient tumor transcriptomes., (©2024 American Association for Cancer Research.)

Complications occurring after lymphodepleting chemotherapy (LDC) may delay chimeric antigen receptor (CAR) T-cell infusion. The effect of these delays on clinical outcomes is unclear. We performed a retrospective analysis of 240 patients with relapsed/refractory large B-cell lymphoma treated with standard-of-care axicabtagene ciloleucel (axi-cel) and identified 40 patients (16.7%) who had delay in axi-cel infusion. Of these, 85% had delay due to infection. At time of LDC initiation, patients with delayed infusion had lower absolute neutrophil count (P=0.006), lower platelets (P=0.004), lower hemoglobin (P<0.001) and higher C-reactive protein (P=0.001) than those with on-time infusion. Patients with delayed infusion had lower day 30 overall response rates (59.0% vs. 79.4%; P=0.008) and shorter median progression-free survival (PFS) (3.5 vs. 8.2 months; P=0.002) and overall survival (7.8 vs. 26.4 months; P=0.046) than those with on-time infusion. The association with PFS was maintained on multivariate analysis. There was also an association between extent of delay and survival, with shorter median PFS in patients who had delays of 2-5 days (1.8 vs. 8.2 months; P=0.001) and >5 days (4.6 vs. 8.2 months; P=0.036), but not 1 day (5.7 vs. 8.2 months; P=0.238). Following propensity score matching, patients with delayed infusion continued to have shorter median PFS (3.5 vs. 6.0 months; P=0.015). Levels of pro-inflammatory cytokines on day of infusion were significantly higher in patients with delayed infusion. Together, these findings suggest that delays in CAR T-cell administration after initiation of LDC are associated with inferior outcomes. Further studies are needed to guide strategies to improve efficacy in such patients.

Purpose: Pancreatic cancer (PC) is a deadly disease most often diagnosed in late stages. Identification of high-risk subjects could both contribute to preventative measures and help diagnose the disease at earlier timepoints. However, known risk factors, assessed independently, are currently insufficient for accurately stratifying patients. We use large-scale data from the UK Biobank (UKB) to identify genetic variant-smoking interaction effects and show their importance in risk assessment., Methods: We draw data from 15,086,830 genetic variants and 315,512 individuals in the UKB. There are 765 cases of PC. Crucially, robust resampling corrections are used to overcome well-known challenges in hypothesis testing for interactions. Replication analysis is conducted in two independent cohorts totaling 793 cases and 570 controls. Integration of functional annotation data and construction of polygenic risk scores (PRS) demonstrate the additional insight provided by interaction effects., Results: We identify the genome-wide significant variant rs77196339 on chromosome 2 (per minor allele odds ratio in never-smokers, 2.31 [95% CI, 1.69 to 3.15]; per minor allele odds ratio in ever-smokers, 0.53 [95% CI, 0.30 to 0.91]; P = 3.54 × 10 -8 ) as well as eight other loci with suggestive evidence of interaction effects ( P < 5 × 10 -6 ). The rs77196339 region association is validated ( P < .05) in the replication sample. PRS incorporating interaction effects show improved discriminatory ability over PRS of main effects alone., Conclusion: This study of genome-wide germline variants identified smoking to modify the effect of rs77196339 on PC risk. Interactions between known risk factors can provide critical information for identifying high-risk subjects, given the relative inadequacy of models considering only main effects, as demonstrated in PRS. Further studies are necessary to advance toward comprehensive risk prediction approaches for PC.

Background: The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population., Methods: The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted., Results: Patients in the lower risk tertile experienced fewer ischemic events with ticagrelor than placebo, whereas there was no significant benefit from ticagrelor in the other tertiles (P interaction  = .008). Bleeding rates were consistently increased with ticagrelor across all tertiles (P interaction  = .79). Ticagrelor reduced NACE in the first tertile (HR = 0.74, 95% CI = 0.61-0.90) but not in the others (HR = 1.03, 95% CI = 0.86-1.23 and HR = 1.05, 95% CI = 0.91-1.22, respectively; P interaction  = .012)., Conclusions: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown., Methods and Results: Concentrations of NT-proBNP, high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 were analyzed in 1448 patients presenting with acute dyspnea from the prospective, multicenter International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all 3 biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in 2 biomarkers (18.8%, 44 of 234), 1 biomarker (3.8%, 10 of 260), or no elevated biomarkers (0.4%, 2 of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite end point of mortality and HF rehospitalization. In adjusted models, patients with one, 2, and 3 elevated biomarkers had 3.74 (95% confidence interval [CI], 1.26-11.1, P = .017), 12.3 (95% CI, 4.60-32.9, P < .001), and 12.6 (95% CI, 4.54-35.0, P < .001) fold increased risk of 180-day mortality or HF rehospitalization., Conclusions: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic, and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)