Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective To investigate the clinical characteristics,diagnosis,treatment,and prognosis of descending necrotizing mediastinitis(DNM)to provide a reference for the early diagnosis and timely treatment of DNM.Methods Data on DNM in China was electronically retrieved from the core databases and comprehensively reviewed from June 2012 to June 2023.The infection,pathogenic microorganisms,main symptoms,comorbidities and treatment methods of DNM were analyzed.Results The data of a total of 781 DNM patients,with an average age of(52.97±5.64)years,were retrieved,including 554 males and 227 females.Odontogenic source,tonsillitis,pharyngeal abscess,sialoadenitis,upper respiratory tract infection,foreign body injury,or iatrogenic traumatic procedures are common causes.Among these,odontogenic infection is the most common source.Streptococcus sp.(n=217)and Staphylococcus sp.(n=82)were most isolated,followed by Klebsiella pneumoniae and Pseudomonas aeruginosa(equally n=59).A total of 69.4％(542/781)of DNM patients recruited in this study were discovered to have various comorbidities,and more than one-third of these patients(n=185)had diabetes.Of the broad antibiotics,carbapenem was most frequently used as treatment,and vancomycin was the most frequently coadministered.The mediastinal drainage approach varies widely,and the optimal regimen is still unknown.Seventy-two patients were treated with video-assisted thoracoscopic/mediastinoscopic surgical drainage,22 patients were treated with percutaneous catheter drainage,30 underwent the transcervical approach,and 40 underwent thoracotomy.A total of 617 patients who were selected underwent the appropriate combined operation for surgical drainage according to the specific location of the infected focus.The overall mortality rate of all 781 DNM pa-tients included was 11.2％.Conclusion The most effective diagnosis and treatment of DNM is a high degree of clini-cal vigilance followed by prompt and adequate drainage with intensive care,including hemodynamic monitoring,nutri-tional support,computer tomographic scanning repeated as necessary,and combined use of systemic antibiotics.

OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

Objective:To investigate the application effect of E-learning digital platform combined with brainstorming teaching in nursing practice teaching of otolaryngology and head and neck surgery.Methods:A total of 41 nursing students who received practice teaching in Qilu Hospital of Shandong University from January 2022 to June 2022 were selected as control group, and 39 nursing students who received practice teaching from July 2022 to December 2022 were selected as observation group. The students in the control group received traditional nursing teaching, while those in the observation group received brainstorming teaching based on the E-learning digital platform. After teaching, the two groups were compared in terms of academic performance, daily problem-solving ability, self-learning ability, critical thinking ability, and degree of satisfaction with teaching. SPSS 24.0 was used to perform the chi-square test and the t-test. Results:Compared with the control group, the observation group had significantly higher theoretical and operational assessment scores [(90.11±5.43)/(88.19±5.33) vs. (82.67±5.09)/(81.33±4.27)], scores of positive problem-solving orientation and rational problem-solving dimensions of the problem-solving questionnaire, scores of each dimension of the self-learning ability scale and the critical thinking ability, and scores of classroom teaching, clinical teaching, support, and resources in the satisfaction scale, as well as significantly lower scores of negative problem orientation, avoidance style, and impulsive neglect style in the problem-solving questionnaire ( P<0.05). The observation group had significantly higher scores of classroom teaching, clinical teaching machine support, and resources than the control group. Conclusions:In the nursing practice teaching of otolaryngology and head and neck surgery, the application of E-learning digital platform combined with brainstorming teaching can effectively improve the performance of nursing interns and strengthen their problem-solving, self-learning, and critical thinking abilities, with a relatively high degree of satisfaction among nursing interns.

AIM:This study aims to investigate the expression differences of the ultraconserved RNA gene cluster uc.102-uc.106 and its host gene Obg-like ATPase 1(OLA1)in various tissues of C57BL/6J mice.METHODS:Five healthy male C57BL/6J mice aged 8～10 weeks were selected,and under normal physiological conditions,various tis-sues and organs,including liver,testis,bone marrow,brain,kidney,blood,lung,colon,thymus,spleen,stomach,heart,lymph nodes and bladder,were collected.Simultaneously,magnetic bead separation technology was employed to extract bone marrow blood cells,including B cells,macrophages,erythroid precursor,and mature red blood cells.The ex-pression levels of uc.102-uc.106 and OLA1 mRNA were determined by RT-qPCR with GAPDH as the internal reference.RESULTS:The OLA1 mRNA exhibited high expression levels in the brain,lymph nodes,testis and thymus of C57BL/6J mice,and low expression levels in the liver,spleen,lung,colon and peripheral blood(P<0.05).The expression trend of the uc.102-uc.106 gene cluster was generally opposite to that of OLA1 mRNA,except for both exhibiting high expression levels in testicular tissue(P<0.05).In blood cells,the OLA1 mRNA and the uc.102-uc.106 gene cluster showed the highest expression levels in B cells and the lowest expression levels in mature red blood cells(P<0.05).CONCLU-SION:This study indicates that OLA1 gene and uc.102-uc.106 gene cluster are expressed in different tissues and blood cells of C57BL/6J mice.Notably,the high expression levels of OLA1 gene and uc.102-uc.106 gene cluster in the mouse testis suggest a potential association with male reproductive functions.

BACKGROUND:In recent years,High-definition transcranial direct current stimulation(HD-tDCS)has garnered significant attention due to its potential non-invasive modulation of brain function.However,there is still a lack of visual analysis in the literature regarding this technique. OBJECTIVE:To perform a visual analysis of HD-tDCS-related research so as to explore the current status and trends in this field. METHODS:English literature related to HD-tDCS was retrieved from the Web of Science Core Collection database covering the period from January 1,2010 to May 6,2023.The VOSviewer software was used to visualize and analyze the source journals,countries/regions,authors,institutions,cited references,and keywords of the included literature,creating a knowledge map to uncover the research landscape and hotspots. RESULTS AND CONCLUSION:A total of 336 articles were included,showing a consistent increase in the annual publication count of HD-tDCS research.Among these,the United States contributed the highest number of publications(141 articles)with 4 221 citations,followed by China with 70 articles and 401 citations.Brain Stimulation was the most prolific journal(28 articles),Marom Bikson was the most productive author(37 articles),and The City College of New York was the most active institution(35 articles).The most frequently mentioned keywords in the field included motor cortex,regulation,working memory,excitability,and dorsolateral prefrontal cortex.Notable recent keywords in the last 5 years include attention-deficit/hyperactivity disorder,brain networks,and stimulation intensity.Currently,the volume of HD-tDCS research is relatively limited,but is on an upward trajectory,indicating substantial research potential.It is expected that future studies in this domain will continue to focus on the application of HD-tDCS in cognitive and neuropsychiatric disorders,while also exploring its therapeutic mechanisms targeting the motor cortex and dorsolateral prefrontal cortex based on brain network analysis.

AIM:To investigate the role of Ywhab in the growth of mouse B-cell lymphoma,and to explore the potential underlying mechanisms.METHODS:The correlation between Ywhab and human diffuse large B-cell lymphoma(DLBCL)was investigated by bioinformatics analysis.Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene,which was verified by RT-qPCR and Western blot.The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting,CCK-8 assay,and subcutaneous tumor loading experiments.The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot.Co-immunoprecipitation combined with mass spectrometry(CoIP-MS)was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β,which was confirmed by Western blot and molecu-lar docking analysis.RESULTS:The Ywhab gene exhibited low expression in DLBCL,which was correlated with poor clinical prognosis of DLBCL patients.Compared with normal mouse bone marrow B cells,Ywhab expression was low in 38B9 cells.Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo,promoted the expression of pro-apoptotic proteins Puma,Noxa and Bax at both mRNA and protein levels,and inhibited the mRNA and protein expres-sion of anti-apoptotic protein Bcl2(P＜0.05).The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels,thereby suppressing the growth of 38B9 cells.CONCLUSION:Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1.

Objective To explore the safety and efficacy of endovascular treatment(EVT)in patients with acute posterior circulation ischemic stroke over 24 hours from onset.Methods This retrospective study retrospectively analyzed patients with acute posterior circulation ischemic stroke who received EVT in the Department of Neurology,First Hospital of Jilin University from June 2018 to June 2023.The patient's gender,age and other related demographic information were collected.The related examination results of patients were collected,including admission rapid blood glucose,admission systolic blood pressure,admission diastolic blood pressure.The related risk factors of stroke of patients were collected,including previous transient ischemic attack,hypertension,diabetes,atrial fibrillation,and history of drinking,smoking history,etc.;other related indicators were collected,including intravenous thrombolysis,tandem lesions,awakening stroke,baseline National Institutes of Health stroke scale(NIHSS)score,and baseline posterior circulation Alberta stroke program early CT score(pc-ASPECTS),collateral circulation grade of American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR),onset to EVT puncture time,the trial of org 10172 in acute stroke treatment(TOAST)classification and outcome indicators(efficacy indicators included 90 days Modified Rankin scale[mRS]score≤3 after EVT,successful recanalization[extended cerebral infarction thrombolytic recanalization class 2b-3];security indexes included symptomatic intracranial hemorrhage[sICH]within 24 h after EVT and 90 d mortality after EVT).According to the symptom onset to EVT puncture time,the patients were divided into two groups:≤24h group and＞24h group.The patients with onset time＞24 h and those with onset time≤24 h were matched at a ratio of 1:1 by propensity score matching(PSM).All patients were divided into poor prognosis group(mRS score＞3)and good prognosis group(mRS score ≤ 3)according to mRS score at 90 days after EVT.Using univariate and multivariate Logistic regression was used to analyze the effect of onset time on clinical outcomes at 90 days after EVT.Results A total of 366 patients were enrolled in this study,including 284 males and 82 females.The median age was 61(55,68)years old,ranging from 25 to 91 years old.Before PSM,the＞24h group had lower prevalence of atrial fibrillation(2.02％[2/99]vs.9.74％[26/267],P=0.025)and lower baseline NIHSS score(10.0[5.0,19.0]vs.14.0[10.0,35.0],P＜0.01)and higher ASTIN/SIR collateral grade(P=0.018).After PSM,we did not find statistical difference between the two groups in baseline characteristics except for the onset to EVT puncture time.Before and after PSM,there was no significant difference in efficacy and safety between the onset time＞24 h group and the onset time ≤24h group.Univariate binary Logistic regression analysis showed that hypertension(OR,0.613,95％CI 0.391-0.942,P=0.025),intravenous thrombolysis(OR,3.235,95％CI 1.316-9.237,P=0.010),baseline NIHSS score(OR,0.975,95％CI 0.957-0.988,P＜0.01),baseline pc-ASPECTS(OR,1.281,95％CI 1.101-1.482,P=0.001)and sICH within 24 h after EVT(OR,0.070,95％CI 0.000-0.330,P＜0.01)were significantly correlated with prognosis.Gender,age,hypertension,baseline NIHSS score,intravenous thrombolysis,baseline pc-ASPECTS,ASTIN/SIR collateral grade,onset time＞24 h and sICH within 24 h after EVT were included in the multivariate binary Logistic regression analysis.The multivariate binary Logistic regression analysis showed that the onset time＞24 h was not associated with poor prognosis 90 d after EVT(aOR,1.635,95％CI 0.936-2.893,P=0.087).Conclusion EVT for acute posterior circulation ischemic stroke more than 24 hours after onset is feasible under strict imaging screening,and its safety and efficacy are similar to those in patients with onset under 24 hours.

Objective:To explore the effectiveness and safety of endovascular treatment (EVT) for patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h.Methods:In this retrospective cohort study, data were extracted from patients who underwent endovascular treatment for acute anterior circulation ischemic stroke at the First Hospital of Jilin University from February 2019 to April 2022. A total of 569 patients were included, with a mean age of 63 (54-70) years. Among them, 398 (69.9%) were male. The patients were divided into two groups based on symptom onset time:>24 h group and≤24 h group. Propensity score matching (PSM) was used to match the patients in a 1︰1 ratio between the>24 h group and the≤24 h group. Logistic regression was used to evaluate the impact of symptom onset time on outcome events.Results:Before PSM, compared with≤24 h group, the>24 h group had a younger age [56 (48, 64) vs. 64 (55, 70), Z=-3. 60, P<0.001]; lower proportion of prior atrial fibrillation [1.8% (1/57) vs. 21.1% (108/512), χ2=12.39, P<0.001]; lower proportion of wake-up stroke [7.0% (4/57) vs. 27.7% (142/512), χ2=11.54, P<0.001]; lower baseline NIHSS score [11.0 (7.5, 14.0) vs. 13.0 (10.0, 16.0), Z=-3.22, P<0.001]; and a higher American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR) grading ( P<0.001). After PSM, there were no significant differences in baseline characteristics between the two groups. There was no significant difference in the proportion of patients with a modified Rankin Scale (mRS) score≤2 at 90 days after surgery between the two groups (before matching: 42.0% vs. 40.4%, OR=0.745, 95% CI 0.407-1.362, P=0.339; after matching: 51.8% vs. 39.3%, OR=0.511, 95% CI 0.212-1.236, P=0.136). No significant differences were observed in the incidence of any safety outcomes between the>24 h group and the≤24 h group. Conclusion:For patients with acute anterior circulation ischemic stroke with symptom onset exceeding 24 h, EVT is feasible after strict radiological screening and has similar safety and effectiveness as for patients with symptom onset under 24 h.

Objective:To explore the correlation between systemic inflammatory response index (SIRI) and clinical outcome of patients with massive cerebral infarction (MCI) after craniotomy and decompression.Methods:The clinical data of 50 MCI patients who were treated in the Affiliated Hospital of Qingdao University from January 2016 to December 2020 and underwent craniotomy and decompression were retrospectively analyzed. The measurement data of normal distribution were expressed as xˉ± s, and the measurement data of non normal distribution were expressed as M( Q1, Q3). T-test or rank sum test was used for comparison between the two groups. Multivariate Logistic regression was used to analyze the relationship between SIRI and prognosis of MCI patients and establish a prediction model. The predictive value and optimal cutoff value of SIRI were analyzed by receiver operating characteristic curve (ROC). Results:Among the 50 MCI patients who underwent craniotomy and decompression, 12 (24%, 12/50) had a good prognosis; In the poor prognosis group, 38 cases (76%, 12/50), of which 9 cases (18%, 9/50) died during hospitalization. The age of patients in the good prognosis group and the poor prognosis group ((54±11) years and (63±9) years; t=2.72, P=0.015), body mass index (BMI): ((23.91±2.64) kg/m 2 and (26.72±3.28) kg/m 2, t=3.01, P=0.006)), neutrophil count (7.08 (5.12, 7.38))×10 9/L and 10.59 (8.91,14.64)×10 9/L, Z=5.72, P<0.001), white blood cell count ((9.09±2.80)×10 9/L and (13.20±3.49) ×10 9/L; t=4.16, P<0.001), SIRI (2.49(1.78, 4.75) and 8.34(5.17, 13.61); Z=3.84, P<0.001), Glasgow Coma Score (12(9,14) and 8(6,10); Z=3.36, P=0.002) and lymphocyte count (1.58(0.91, 1.91)×10 9/L and 0.77(0.59,1.02) ×10 9/L; Z=3.30, P=0.001).The difference between the two groups was statistically significant. The prognosis of patients with dominant hemisphere infarction was worse than that of patients with non-dominant hemisphere infarction (22 cases (91.67%, 22/24) vs. 16 cases (61.54%, 16/26); χ 2=6.21, P=0.013). The ICU stay in the good prognosis group was significantly shorter than that in the poor prognosis group (2 (1, 5) days vs. 8 (3, 19) days; Z=2.78, P=0.005). Multivariate Logistic regression analysis showed that SIRI and GCS were correlated with clinical prognosis: SIRI ( OR: 2.378; 95% CI: 1.131-5.003; P=0.022); GCS at admission ( OR: 0.548; 95% CI: 0.307-0.980; P=0.043). The ROC curve analysis of SIRI prediction of poor prognosis: Area under the curve (AUC): 0.871, (95% CI: 0.765-0.976, P<0.001), sensitivity was 78.9%, specificity was 88.3%, and the optimal cut-off value was 4.96. The sensitivity, specificity and AUC of GCS for predicting poor prognosis after MCI craniotomy decompression were 89.5%, 58.3% and 0.791 (95% CI: 0.638~0.943, P=0.003), and the best truncation value was 11.5. Conclusion:SIRI was an effective predictor of clinical outcome for MCI patients underwent Craniotomy for decompression, and SIRI value greater than 4.96 indicates adverse clinical outcome.