Immunomodulation in non-alcoholic fatty liver disease: exploring mechanisms and applications.

Non-alcoholic fatty liver disease (NAFLD) exhibits increased lipid enrichment in hepatocytes. The spectrum of this disease includes stages such as nonalcoholic simple fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and liver fibrosis. Changes in lifestyle behaviors have been a major factor contributing to the increased cases of NAFLD patients globally. Therefore, it is imperative to explore the pathogenesis of NAFLD, identify therapeutic targets, and develop new strategies to improve the clinical management of the disease. Immunoregulation is a strategy through which the organism recognizes and eliminates antigenic foreign bodies to maintain physiological homeostasis. In this process, multiple factors, including immune cells, signaling molecules, and cytokines, play a role in governing the evolution of NAFLD. This review seeks to encapsulate the advancements in research regarding immune regulation in NAFLD, spanning from underlying mechanisms to practical applications.

Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma.

Histone lysine lactylation (Kla) plays a vital role in the tumorigenesis of hepatocellular carcinoma (HCC). Hence, we focused on Kla-specific genes to select novel therapeutic targets. Differentially expressed Kla-specific genes (DEKlaGs) were identified from TCGA with the cut-off criteria |log2(FlodChange (FC))| > 2, p-value < 0.05, following investigating the prognostic value. The correlation between lactate accumulation and prognostic DEKlaGs expression was further investigated. On the other hand, we explored the roles of Kla activation in the immune microenvironment, immunotherapy, and drug resistance. We conducted gene set enrichment analysis (GSEA) to predict the pathways influenced by Kla. The predictive power of Cox model was further identified in ICGC and GEO databases. A total of 129 DEKlaGs were identified, and 32 molecules might be potential prognostic biomarkers. A Cox model including ARHGEF37, MTFR2, NR6A1, NT5DC2, OSBP2, RNASEH2A, SFN, and UNC119B was constructed, which suggested unfavorable overall survival in high-risk score group, and risk score could serve as an indicator for large tumor size, poor pathological grade and advanced stage. NR6A1, OSBP2 and UNC119B could inhibit NK cell as well as TIL cell infiltration, and impair Type-I and II IFN responses in HCC, thereby contributing to unsatisfactory prognosis and immunotherapy resistance. OSBP2 and UNC119B were identified to be related to chemotherapy resistance. GSEA showed that WNT, MTOR, MAPK and NOTCH signaling pathways were activated, indicating that these pathways might play a crucial role during the Kla process. On the other hand, we showed that NR6A1 and OSBP2 were overexpressed in GEO. OSBP2 and UNC119B contributed to poor survival and advanced stage in ICGC. In summary, histone Kla was related to HCC prognosis and might serve as an independent biomarker. NR6A1, OSBP2 and UNC119B were associated with the prognosis, immunotherapy, and chemotherapy resistance, suggesting that NR6A1, OSBP2 and UNC119B might be novel candidate therapeutic targets for HCC.

Advanced maternal age: copy number variations and pregnancy outcomes.

Objective: Adverse pregnancy outcomes are closely related to advanced maternal age (AMA; age at pregnancy ≥35 years). Little research has been reported on aneuploid abnormalities and pathogenic copy number variations (CNVs) affecting pregnancy outcomes in women with AMA. The purpose of this study was to assess CNVs associated with AMA in prenatal diagnosis to determine the characteristics of pathogenic CNVs and assist with genetic counseling of women with AMA. Methods: Among 277 fetuses of women with AMA, 218 (78.7%) were isolated AMA fetuses and 59 (21.3%) were non-isolated AMA fetuses and showed ultrasound anomalies from January 2021 to October 2022. Isolated AMA was defined as AMA cases without sonographic abnormalities. Non-isolated AMA was defined as AMA cases with sonographic abnormalities such as sonographic soft markers, widening of the lateral ventricles, or extracardiac structural anomalies. The amniotic fluid cells underwent routine karyotyping followed by single nucleotide polymorphism array (SNP-array) analysis. Results: Of the 277 AMA cases, karyotype analysis identified 20 chromosomal abnormalities. As well as 12 cases of chromosomal abnormalities corresponded to routine karyotyping, the SNP array identified an additional 14 cases of CNVs with normal karyotyping results. There were five pathogenetic CNVs, seven variations of uncertain clinical significance (VOUS), and two benign CNVs. The detection rate of abnormal CNVs in non-isolated AMA cases was increasing (13/59; 22%) than in isolated AMA cases (13/218; 5.96%) (p < 0.001). We also determined that pathogenic CNVs affected the rate of pregnancy termination in women with AMA. Conclusion: Aneuploid abnormalities and pathogenic CNVs affect pregnancy outcomes in women with AMA. SNP array had a higher detection rate of genetic variation than did karyotyping and is an important supplement to karyotype analysis, which enables better informed clinical consultation and clinical decision-making.

Comparison of immune cell profiles associated with heatstroke, sepsis, or cardiopulmonary bypass: Study protocol for an exploratory, case-control study trial.

Introduction: Heatstroke is a life-threatening illness involving extreme hyperthermia and multi-organ failure, and it is associated with high mortality. The immune profiles of heatstroke have not been fully elucidated, and diagnostic and prognostic biomarkers of heatstroke are lacking. This study will analyze immune profiles in heatstroke patients as they differ from profiles in patients with sepsis or aseptic inflammation patients in order to identify diagnostic and prognostic biomarkers. Methods: This exploratory, case-control study will recruit patients with heatstroke, patients with sepsis, patients undergoing cardiopulmonary bypass as well as healthy controls at West China Hospital of Sichuan University from 1 January 2023 to 31 October 2023. The four cohorts will be profiled at one time point in terms of lymphocytes, monocytes, natural killer cells, and granulocytes using flow cytometry, and cell populations will be visualized in two dimensions using t-SNE and UMAP, then clustered using PhenoGraph and FlowSOM. Gene expression in the specific immune cell populations will also be compared across the four cohorts, as will levels of plasma cytokines using enzyme-linked immunosorbent assays. Outcomes in the cohorts will be monitored during 30-day follow-up. Discussion: This trial is, to our knowledge, the first attempt to improve the diagnosis of heatstroke and prediction of prognosis based on immune cell profiles. The study is also likely to generate new insights into immune responses during heatstroke, which may help clarify the disease process and lay the foundation for immunotherapies.

Stock Index Prediction Based on Time Series Decomposition and Hybrid Model.

The stock index is an important indicator to measure stock market fluctuation, with a guiding role for investors' decision-making, thus being the object of much research. However, the stock market is affected by uncertainty and volatility, making accurate prediction a challenging task. We propose a new stock index forecasting model based on time series decomposition and a hybrid model. Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) decomposes the stock index into a series of Intrinsic Mode Functions (IMFs) with different feature scales and trend term. The Augmented Dickey Fuller (ADF) method judges the stability of each IMFs and trend term. The Autoregressive Moving Average (ARMA) model is used on stationary time series, and a Long Short-Term Memory (LSTM) model extracts abstract features of unstable time series. The predicted results of each time sequence are reconstructed to obtain the final predicted value. Experiments are conducted on four stock index time series, and the results show that the prediction of the proposed model is closer to the real value than that of seven reference models, and has a good quantitative investment reference value.

Synthesis of sevoflurane loaded reduced graphene oxide nanoparticles system for neuroprotective effects for preconditioning against focal cerebral ischaemia.

In this study, sevoflurane (SF) loaded, Fas ligand conjugated reduced graphene oxide (rGO) system is fabricated as a therapeutic agent to target brain ischaemic region. The fluorescence investigation of mice brain denoted that the encapsulated SF in rGOs adsorbed with Fas ligand antibody could be significantly distributed to the ipsilateral side of the ischaemic brain. In addition, the immune-histochemical assay presented that the specific nanoparticles especially deposited in the ischaemic part of the tested mice model. Furthermore, SF encapsulated rGO system exhibited noticeable progress in the brain damage along with neurological deficit post ischaemia with limited dosages in contrast to regular SF. Additionally, Rhodamine labelled nanoparticles were used to find whether Fas ligand antibody has the ability to lead the SF-encapsulated nano rGO to enter the ischaemic part of brain as well as carry out neuro-protection. Overall, these experimental findings suggested that rGOs conjugated Fas ligand system could be treated as an ideal brain targeting drug for cerebral ischemia.

[Systematic review of transfusion strategies for cardiac surgery].

This paper is aimed to assess the effects of red blood cell (RBC) transfusion on clinical outcomes in cardiac surgery. Trials were identified by computer searches of the Pubmed, MEDLINE, Cochrane Library (Issue 10, 2012), from January 1980 to October 2012. References in identified trials and review articles were checked and experts contacted to identify any additional trials. The homogeneous randomized controlled trials (RCTs) were analyzed with RevMan 5.1 software. Five trials involving a total of 1,203 patients were identified. The results of meta-analyses showed that restrictive transfusion strategies reduced the risk of receiving a RBC transfusion (MD = - 1.46, 95% CI -1.18(-) -1.1) and the volume of RBCs transfusion (RR = 0.69, 95% CI 0.53-0.89). No significant difference was noted between the two strategies in terms of mortality, adverse events and hospital or intensive care length of stay. Based on the results mentioned above, one can draw a conclusion that restrictive transfusion strategies reduced the risk of receiving RBC transfusion and the volume of RBCs transfused. Restrictive transfusion strategies did not appear to impact on the rate of adverse events and hospital or intensive care length of stay, compared to liberal transfusion strategies.

[Relationship between episodic memory and resting-state brain functional connectivity network in patients with Alzheimer's disease and mild cognition impairment].

OBJECTIVE: To explore the relationship between the scores of episodic memory (EM) encoding and retrieving and the resting-state changes of brain functional connectivity (FC) network of Alzheimer's disease (AD) and mild cognition impairment (MCI) patients. METHODS: All subjects were recruited from special care clinic and ward and health physical examination center, Qingdao Huanxiu Community and Affiliated Hospital, Medical College of Qingdao university from January 2009 to July 2012.They were divided into AD group (n = 16), MCI group (n = 24) and normal control (NC) group (n = 24). The resting-state fMRI scans were performed with GE3.0T to acquire the blood oxygenation level dependent signals for EM encoding and retrieving. The two-sample t test was conducted between the groups and linear correlation analysis performed between EM and FC. RESULTS: Compared to the NC group, the AD and MCI groups exhibited decreased FC to posterior cingulated cortex (PCC) mainly in bilateral lateral temporal lobe, medial prefrontal cortex and right insula.Increased regions existed in posterior cerebellar lobe. Compared with the MCI group, the AD group showed decreased FC to PCC in medial prefrontal cortex, bilateral insulas, right inferior temporal gyrus and right fusiform gyrus.And increased regions lied in posterior cerebellar lobe, right occipital lobe and left superior parietal lobule. Compared with the NC group, the MCI group exhibited decreased FC to PCC in left lingualis gyrus, left frontal lobe, right middle temporal gyrus and corpus callosum.And increased regions lied in posterior cerebellar lobe.EM encoding scores (%) (AD group 34 ± 20, MCI group 47 ± 17, NC group 69 ± 15) were significantly different among three groups (P < 0.05).And retrieving scores (%) (AD group 31 ± 18, MCI group 57 ± 22, NC group 81 ± 16) were significantly different among three groups (P < 0.05). Altered functional connectivity regions of left triangle orbital-inferior frontal gyrus (r = 0.642 98), left cuneus (r = 0.642 98) and left caudate nucleus (r = 0.642 68) showed positive correlations with the EM encoding scores in AD group (all P < 0.005). Other groups were not statistically significant. CONCLUSION: The resting-state FC networks of AD and MCI groups show significant differences. The MCI and AD patients have progressively decreased scores of episodic memory encoding and retrieving.And the declines of episodic memory encoding and partial regions of resting-state FC network are positively correlated in the AD group.