Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

BACKGROUND:Animal models of diabetic encephalopathy that have been studied mainly include streptozotocin-induced model,high-sugar and high-fat diet-induced model and spontaneous animal model.Establishing a simple,easy,short-cycle,safe and effective model of diabetic encephalopathy can help to explore the subsequent pathogenesis and screen therapeutic drugs. OBJECTIVE:To further explore and evaluate the method of building diabetic encephalopathy rat models. METHODS:Twenty Sprague-Dawley rats were randomly divided into control(n=10)and model(n=10)groups.Rats in the model group were given a single injection of 45 mg/kg streptozotocin in the left lower abdominal cavity,and those in the control group were given the same amount of citrate buffer.During the experiment,the body mass,feed intake,water intake and blood glucose were measured.After 8 weeks,the glucose tolerance and oxidative stress levels were measured,and the pathological changes of brain tissue and the expression of apoptotic proteins were compared between groups. RESULTS AND CONCLUSION:Compared with the control group,the food intake,water intake,encephalization quotient,blood glucose and area under the blood glucose curve were significantly increased in the model group,while the body mass decreased significantly(P<0.01).Histopathological examination of the brain showed that compared with the control group,the number of surviving nerve cells was significantly reduced in the model group(P<0.01),with more significant pathological damage of nerve cells.Compared with the control group,the activities of serum superoxide dismutase,catalase and glutathione in the model group were significantly decreased(P<0.01),and the content of oxidative malondialdehyde was significantly increased(P<0.05).The expression levels of apoptosis-related proteins Bax and Caspase-3 in brain tissue increased in the model group compared with the control group,while the expression of Bcl-2 decreased(P<0.01).In conclusion,an 8-week injection of 45 mg/kg streptozotocin can cause obvious pathological damage to the brain tissue of diabetic rats,to successfully establish the rat model of diabetic encephalopathy.

Currently,electroencephalogram(EEG),functional near-infrared spectroscopy(fNIRS),and functional magnetic resonance imaging have been widely studied and applied to neuropsychiatric disorders.In recent years,the devices which can realize the simultaneous acquisition of EEG and fNIRS has been developed and gradually applied in the studies on neuropsychiatric disorders.The review provides an introduction of the techniques of synchronized detection and data analysis for EEG-fNIRS,summarizes the analysis methods and new findings of the recent studies of stroke,epilepsy,and other neuropsychiatric disorders using EEG-fNIRS,and also discusses the future research directions.

Objective To explore the value of automatic segmentation technique combined with neurite dispersion and density imaging(NODDI)for displaying volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy(mTLE-HS).Methods MRI data of 33 patients with left mTLE-HS(mTLE-HS group)and 35 healthy adults(control group)were retrospectively analyzed.The hippocampal subregions were automatically segmented using FreeSurfer software,the volume of cornu Ammonis(CA)1,CA2-3,CA4,granulose cell-dentate gyrus(GC-DG)and subiculum were measured,then the NODDI parameters of each subregion were obtained through post-processing.The intra-and inter-groups hippocampal subregion volumes and NODDI parameters were compared,and the correlations of parameters being significantly different with the onset age and disease courses were analyzed.Results The volume of hippocampal subregions in mTLE-HS group were all lower than those in control group(all P＜0.05).In mTLE-HS group,the neurite density index(NDI)of left CA1 and CA4 subregions were both lower,while the free-water isotropic volume fraction(fiso)of the left CA1 subregion was higher than those of the right side(all P＜0.05).The orientation dispersion index(ODI)of left CA1,CA2-3 and CA4 subregions,as well as NDI of left CA1,CA4 and GC-DG subregions in mTLE-HS group were all lower than those in control group(all P＜0.05),while fiso of left CA1,GC-DG and subiculum subregions in mTLE-HS group were all higher than those in control group(all P＜0.05).The volume of left hippocampal subregions in patients with mTLE-HS were all moderately positively correlated with the onset age(r=0.540-0.667,all P＜0.001)but weakly negatively correlated with disease courses(r=-0.492--0.386,all P＜0.05).NDI of left CA4 and GC-DG subregions in patients with mTLE-HS were both weakly negatively correlated with disease courses(r=-0.418,-0.388,both P＜0.05).Conclusion Automatic segmentation technique combined with NODDI could be used to display the volume and microstructure changes of mTLE-HS.NDI might be a biomarker of mTLE-HS being sensitive to progressive neuronal damage.

Objective To explore the hippocampal(HC)microstructural changes in patients with unilateral temporal lobe epilepsy(TLE)by neurite orientation dispersion and density imaging(NODDI).Methods The NODDI indexes of the whole HC and HC subregions of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)patients,non-HS patients and healthy controls(control group)were calculated.The differences of NODDI indexes among and within the three groups were compared,and the correlation between the difference indexes and the clinical characteristics of the patients was analyzed.Results A total of 47 patients with TLE(27 cases of TLE-HS,20 cases of non-HS)and 22 cases of healthy controls were enrolled.In the TLE-HS group,the free-water isotropic vol-ume fraction(fiso)values of the HC and granular cell layer of dentate gyrus(GC-DG)subregions of the affected side were signifi-cantly higher than those of the contralateral side;the orientation dispersion index(ODI)values of the CA1 and CA4 subregions were significantly lower than those of the contralateral side;and the neurite density index(NDI)values of the HC,CA1,CA2-3,CA4 and GC-DG subregions of the affected side decreased significantly.There was no significant difference between the affected side and the contralateral side in the non-HS group.The fiso values of the HC and GC-DG subregions of the affected side in the TLE-HS group were significantly higher than those in the control group,the ODI values of the HC CA1 subregions of the affected side in the TLE-HS group were significantly lower than those in the control group and the non-HS group,the NDI values of the HC and subiculum(Sub),CA1,CA4 and GC-DG subregions of the affected side in the TLE-HS group were significantly lower than those in the con-trol group,and the NDI values of the HC and CA1,CA4 and GC-DG subregions of the affected side in the non-HS group were significantly lower than those in the control group.In the TLE-HS group,the NDI value of the HC CA4 subregion of the affected side was negatively correlated with the disease course,but there was no clear correlation between other subregion variables and disease course,onset frequency and duration of single onset.Conclusion NODDI technique has the ability to detect the microstructural changes of HC in patients with TLE,among which NDI is more likely to highlight neuronal damage and fiber reorganization in patients with TLE.

Industry-university-research cooperation is not only the core of technological innovation,but also an important way to enhance industrial competitiveness and achieve high-quality development.Industry-university-research cooperation in Liaoning Province has achieved significant results in promoting technological innovation and economic development,but there are still some problems and challenges.The main problems include insufficient depth of industry-university-research cooperation,scattered innovation resources,lack of long-term stable cooperation mechanisms,as well as talent loss and lack of high-quality innovative talents.Through systematically sorting out the existing models of industry-university-research cooperation,it proposes a series of targeted and operable countermeasures and suggestions.These measures and suggestions provide solid theoretical support for the healthy development of industry-university-research cooperation in Liaoning Province.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To evaluate the effect of esketamine combined with ultrasound-guided dorsal penile nerve block (DPNB) on negative postoperative behavioral changes (NPOBCs) in pediatric patients undergoing circumcision under general anesthesia.Methods:One-hundred and ninety-five pediatric patients, aged 4-8 yr, with body mass index of 10-35 kg, of American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ, undergoing elective circumcision under general anesthesia, were selected and divided into 3 groups ( n=65 each) using a random number table method: esketamine group (group E), DPNB group (group D) and esketamine combined with DPNB group (group ED). Propofol 1.5 mg/kg was intravenously injected, and the patients were admitted to the operating room after consciousness disappeared in the 3 groups. Esketamine 0.5 mg/kg was intravenously injected in E and ED groups, and the equal volume of normal saline was given in group D. D and ED groups underwent bilateral DPNB with 0.25 % ropivacaine 0.15 ml/kg under ultrasound guidance, with the maximum total amount of the drug not exceeding 10 ml. Fentanyl 1.0 μg/kg and propofol 2.0 mg/kg were intravenously injected prior to the skin incision in the three groups. If intraoperative body movement occurred, propofol 10 mg was added, which could be repeated. The occurrence of intraoperative body movement, respiratory depression and amount of propofol added was recorded. When postoperative pain (FLACC score >4) occurred, flurbiprofen 1 mg/kg was intravenously injected for analgesia, and the usage of flurbiprofen was recorded. When emergence agitation(PEAD score>10) occurred, propofol 1 mg/kg was intravenously injected for sedation, and the occurrence of emergence agitation was recorded. Parents were followed up by telephone at 1, 7 and 30 days postoperatively to assess the occurrence of NPOBCs using the PHBQ scale. Results:Fifty-six patients in group E and 59 patients in D and ED groups finally completed the study.Compared with group E, the incidence of intraoperative body movement was significantly decreased, the amount of additional propofol was reduced, the emergence agitation score, incidence of emergence agitation and severe agitation and usage rate of postoperative flurbiprofen were decreased, and the incidence of separation anxiety at 7 and 30 days postoperatively was decreased in D and ED groups, and the incidence of intraoperative respiratory depression was significantly decreased, and the incidence of NPOBCs at 7 and 30 days postoperatively was decreased in group ED ( P<0.05). Compared with group D, the incidence of intraoperative respiratory depression was significantly decreased, the amount of additional propofol was decreased, the usage rate of postoperative flurbiprofen and incidence of sleep anxiety at 1 day postoperatively were decreased ( P<0.05), and no significant change was found in the incidence of NPOBCs at each time point after operation in group ED ( P>0.05). Conclusions:Esketamine combined with ultrasound-guided DPNB can reduce the occurrence of NPOBCs in pediatric patients undergoing circumcision under general anesthesia.

OBJECTIVE: To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects. METHODS: Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice. RESULTS: Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis. CONCLUSION Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans ; Animals ; Mice ; MicroRNAs/metabolism* ; Cell Line, Tumor ; Cell Proliferation/physiology* ; Mice, Nude ; Cell Movement/physiology* ; Colorectal Neoplasms/pathology* ; Luciferases/metabolism* ; Gene Expression Regulation, Neoplastic ; PTEN Phosphohydrolase/metabolism* ; Chemokine CXCL12/metabolism*