Armillariella tabescens-derived polysaccharides alleviated â±°-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway.

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Effect of anticoagulation on the incidence of venous thromboembolism, major bleeding, and mortality among hospitalized COVID-19 patients: an updated meta-analysis.

Objective: Anticoagulation is crucial for patients hospitalized with coronavirus disease 2019 (COVID-19) due to the high risk of venous thromboembolism (VTE). However, the optimal anticoagulation regimen needs further exploration. Therefore, we evaluated the efficacy and safety of diverse anticoagulation dosage dosages for COVID-19. Methods: An updated meta-analysis was performed to assess the effect of thromboprophylaxis (standard, intermediate, and therapeutic dose) on the incidence of VTE, mortality and major bleeding among COVID-19 patients. Literature was searched via PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI) database. The odds ratio (OR) and 95% confidence interval (CI) were calculated for effect estimates. Results: Nineteen studies involving 25,289 participants without VTE history were included. The mean age of patients was 59.3 years old. About 50.96% were admitted to the intensive care unit. In the pooled analysis, both therapeutic-dose and intermediate-dose anticoagulation did not have a significant advantage in reducing VTE risk over standard dosage (OR = 1.09, 95% CI: 0.58-2.02, and OR = 0.89, 95% CI: 0.70-1.12, respectively). Similarly, all-cause mortality was not further decreased in either therapeutic-dose group (OR = 1.12, 95% CI: 0.75-1.67) or intermediate-dose group (OR = 1.34, 95% CI: 0.83-2.17). While the major bleeding risk was significantly elevated in the therapeutic-dose group (OR = 2.59, 95%CI: 1.87-3.57) as compared with the standard-dose regimen. Compared with intermediate dosage, therapeutic anticoagulation did not reduce consequent VTE risk (OR = 0.85, 95% CI: 0.52-1.38) and all-cause mortality (OR = 0.84, 95% CI: 0.60-1.17), but significantly increased major bleeding rate (OR = 2.42, 95% CI: 1.58-3.70). In subgroup analysis of patients older than 65 years, therapeutic anticoagulation significantly lowered the incidence of VTE in comparation comparison with standard thromboprophylaxis, however, at the cost of elevated risk of major bleeding. Conclusion: Our results indicated that for most hospitalized patients with COVID-19, standard-dose prophylactic anticoagulation might be the optimal choice. For elderly patients at low risk of bleeding, therapeutic-dose anticoagulation could further reduce VTE risk and should be considered especially when there were other strong risk factors of VTE during hospital stay. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier, CRD42023388429.

Association of interleukin-6, ferritin, and lactate dehydrogenase with venous thromboembolism in COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is frequntly accompanied by venous thromboembolism (VTE), and its mechanism may be related to the abnormal inflammation and immune status of COVID-19 patients. It has been proved that interleukin-6 (IL-6), ferritin and lactate dehydrogenase (LDH) may play an important role in the occurrence of VTE in COVID-19 infection. But whether they can server as predictors for VTE in COVID-19 is still unclear. In this study, we performed a systematic review and meta-analysis to compare IL-6, ferritin and LDH in VTE and non-VTE COVID-19 patients in order to shed light on the prevention and treatment of VTE. METHODS: Related literatures were searched in PubMed, Embase, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), WANGFANG. COVID-19 patients were divided into VTE group and non-VTE group. Meta-analysis was then conducted to compare levels of IL-6, ferritin and LDH between the two groups. RESULTS: We finally included and analyzed 17 literatures from January 2019 to October 2022. There was a total of 7,035 COVID-19 patients, with a weighted mean age of 60.01 years. Males accounted for 62.64% and 61.34% patients were in intensive care unit (ICU). Weighted mean difference (WMD) of IL-6, ferritin and LDH was 31.15 (95% CI: 9.82, 52.49), 257.02 (95% CI: 51.70, 462.33) and 41.79 (95% CI: -19.38, 102.96), respectively. The above results indicated that than compared with non-VTE group, VTE group had significantly higher levels of IL-6 and ferritin but similar LDH. CONCLUSION: This systematic review and meta-analysis pointed out that elevated levels of IL-6 and ferritin were significantly possitive associated with VTE, thus could be used as biological predictive indicators of VTE among COVID-19 patients. However, no association was found between level of LDH and VTE. Therefore, close monitoring of changes in IL-6 and ferritin concentrations is of great value in assisting clinicans to rapidly identify thrombotic complications among COVID-19 patients, hence facilitating the timely effective managment. Further studies are required in terms of the clinical role of cytokines in the occurrence of VTE among COVID-19 infection, with more reliable systematic controls and interventional trials.

Studies on Pain Associated with Anxiety or Depression in the Last 10 Years: A Bibliometric Analysis.

Background: The prevalence of pain comorbid and anxiety/depression in clinical observations has been high, and the number of related publications has increased in recent years. Nevertheless, few studies have used bibliometric methods to analyze the scientific research on comorbid pain and depression/anxiety. The aim of this study was to systematically examine the trends in global scientific research on comorbid pain and depression/anxiety from 2012 to 2022. Methods: Papers published between 2012 and 2022 were identified in the Web of Science database. Publications that examined comorbid pain and depression/anxiety were included. The language was limited to English. CiteSpace, Excel and VOSviewer were used to analyze the volume of publications, countries, institutions, authors, cocited authors, and keywords. Results: A total of 30,290 papers met the inclusion criteria of the study. Using CiteSpace, VOSviewer and Excel, the results showed that the United States (10,614 publications), Harvard University (1195 publications), and Jensen, Mark P. (77 publications) were the most productive country, institution, and author, respectively. The hotspots and frontiers were "relationship between depression and pain", "gender differences in pain and depression/anxiety domains", "study of specific pain types with depression/anxiety", "treatment of pain combined with anxiety/depression", and "effects of COVID-19 on patients with pain combined with depression/anxiety". Conclusion: These findings indicate a growing interest in the field of comorbid pain and depression/anxiety. The research has been broad and deep, but there is still much room for growth. Furthermore, there is a need for more mature global collaborative networks as well as more high-quality research results in the future.

Case report: Clinical management of recurrent small cell lung cancer transformation complicated with lung cancer-induced acute pancreatitis after lung adenocarcinoma surgery.

In the diagnosis and treatment of non-small cell lung cancer (NSCLC), the histological type may change from lung adenocarcinoma to lung squamous cell cancer or small cell lung cancer (SCLC). Pancreatic metastasis is extremely rare in advanced lung cancer, and pancreatitis characterized by lung cancer metastasis-induced acute pancreatitis (MIAP) is more rare. This paper reports in detail the clinical diagnosis and treatment of a female patient with lung adenocarcinoma who relapsed after radical surgery and progressed after multiple treatments. A second pathological biopsy revealed SCLC transformation, and the patient developed pancreatic metastasis and lung cancer MIAP during follow-up treatment. This paper mainly suggests that clinicians should pay attention to the possibility of pathological type transformation in the progression of advanced NSCLC, closely observe the dynamic changes of tumor markers and pay attention to the re-biopsy pathological analysis. In addition, it provides clinical experience and scientific reference for the discovery, diagnosis and treatment of transforming SCLC and lung cancer MIAP.

Molecular classification and subtype-specific drug sensitivity research of uterine carcinosarcoma under multi-omics framework.

OBJECTIVE: Uterine carcinosarcomas (UCSs) are aggressive rare tumors recognized as malignancies composed of metaplastic transformation of epithelial elements. Nay no comprehensive molecular classification has been applied to UCS to guide targeted therapies so far, which motivated us to subtyping UCS by aggregating multiple genomic platform data. METHODS: We classified UCS into three distinct subtypes with different clinicopathologic and molecular characterization by using similarity network fusion under consensus clustering framework (SNFCC+) to aggregate four genomic data platforms of 55 UCS patients. Differences across subtypes were extracted by functional enrichment, gene mutations and clinical features. Subtypes were further distinguished by putative biomarkers. We also determined associations between individual oncogenes and chemotherapeutics to discuss subtype-specific drug sensitivity. RESULTS: Functional enrichment analysis of the subtype-specific differential expression genes endowed three subtypes new designation: Myo, Cell and Hormone. Mutations in PTEN, PIK3CA, ARID1A and PPP2R1A altered across subtypes. The epithelial-to-mesenchymal transition (EMT) score distinguished Myo from another two subtypes whereby a high EMT scores prevalently existed and each case was judged as M (mesenchymal) phenotype in Myo subtype. Through the drug sensitivity analysis, we found that the response to - tinib drugs is quite different across subtypes according to expression level. Additionally, different subtypes' response to broad-spectrum anti-cancer drug paclitaxel may be also different. CONCLUSIONS: In this study, we identified three distinct molecular subtypes of UCS with different features. Subtypes were also revealed to have different sensitivity to existing chemotherapy drugs, which may support in-depth study of subtype-specific dosing regimens.

Molecular classification and subtype-specific characterization of skin cutaneous melanoma by aggregating multiple genomic platform data.

PURPOSE: Traditional classification of melanoma is widely utilized with little apparent results making the development of robust classifiers that can guide therapies an urgency. Successful seminal research on classification has provided a wider understanding of cancer from multiple molecular profiles, respectively. However, it may ignore the complementary nature of the information provided by different types of data, which motivated us to subtype melanoma by aggregating multiple genomic platform data. METHODS: Aggregating three omics data of 328 melanoma samples, melanoma subtyping was performed by three clustering methods. Differences across subtypes were extracted by functional enrichment, epigenetically silencing, gene mutations and clinical features. Subtypes were further distinguished by putative biomarkers. RESULTS: Functional enrichment of the subtype-specific differential expression genes endowed subtypes new designation: immune, melanin and ion, in which the first subtype was enriched for immune system, the second was characterized by melanin and pigmentation, and the third was enriched for ion-involved transmission process. Subtypes also differed in age, Breslow thickness, tumor site, mutation frequency of BRAF, PTGS2, CDKN2A, CDKN2B and incidence of epigenetically silencing for IL15RA, EPSTI1, LXN, CDKN1B genes. CONCLUSIONS: Skin cutaneous melanoma can be robustly divided into three subtypes by SNFCC+. Compared with the TCGA classification derived from gene expression, the subtypes we presented share concordance, but new traits are excavated. Such a genomic classification offers insights to further personalize therapeutic decision-making and melanoma management.

Soy fiber improves weight loss and lipid profile in overweight and obese adults: a randomized controlled trial.

SCOPE: Studies have suggested that food rich in dietary fiber may facilitate body weight loss, lower total and LDL-cholesterol levels, and reduce body fat. This study examined the effects of soy fiber (SF) on body weight, body composition, and blood lipids in overweight and obese participants. METHODS AND RESULTS: Thirty-nine overweight and obese college adults (19-39 years of age) were randomly assigned to consume control biscuits or biscuits supplemented with SF for their breakfast for 12 wk (approximately 100 g/day). There were significant differences in changes on body weight, BMI, and LDL-cholesterol (LDL-C) between the two groups after 12-wk intervention (p < 0.05). The changes of body weight, BMI, waist circumference, diastolic blood pressure, serum levels of total cholesterol, LDL-C, and glucose, body fat, and trunk fat of participants in SF group were observed significantly after 12 wk. CONCLUSION: SF had favorable effects on body weight, BMI, and fasting LDL-C levels in overweight and obese adults. These effects may be beneficial in antiobesity and the improvement of hyperlipidemia and hypertension (ClinicalTrials.gov registration number-NCT01802840).