Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies.
Animals ; Alzheimer Disease/pathology* ; Pseudogenes/genetics* ; Mice ; Memory Disorders/metabolism* ; MicroRNAs/genetics* ; Disease Models, Animal ; Spatial Learning/physiology* ; Mice, Transgenic ; Presenilin-1/genetics* ; Male ; Amyloid Precursor Protein Secretases/metabolism* ; Mice, Inbred C57BL ; Aspartic Acid Endopeptidases/metabolism*

Objective To explore the application of diagnostic system with artificial intelligence(AI)in the evaluation of patients with coronary heart disease(CHD)at high altitude.Methods A total of 318 pa-tients underwent coronary CT angiography(CTA)at the hospital from January to December 2022 were pro-spectively collected.According to the altitude gradient,the patients were divided into the 2 000-3 000 m group and>3 000 m group.Coronary angiography(CAG)was used as the gold standard to verify the diag-nostic performance of AI diagnostic system.Coronary artery diagnosis system with AI technology and CT de-rived fractional flow reserve(CT-FFR)measurement system were used to evaluate the plaque structure char-acteristics and hemodynamic changes in the two groups of patients.Results Calcified plaques and vulnerable plaques in the>3 000 m group were more than those in the 2 000-3 000 m group(χ2=3.976,6.482,P= 0.046,0.011).The incidence of multi-vessel coronary artery disease,moderate stenosis,severe stenosis and complete occlusion in the>3 000 m group was higher than that in the 2 000-3 000 m group,and the inci-dence of single-vessel coronary artery disease and mild stenosis in the 2 000-3 000 m group was higher than that in the>3 000 m group(P<0.05).The incidence of CT-FFR≤0.80 and<0.70 in the>3 000 m group was higher than that in the 2 000-3 000 m group(χ2=4.782,28.118,P=0.029,<0.001).The comparison with the gold standard showed that this method has high sensitivity,specificity,and diagnostic consistency(P<0.001).Conclusion The coronary diagnosis system with AI technology has certain value in the system-atic evaluation of coronary artery characteristics and hemodynamic changes in CHD patients at high altitude.

Objective To utilize sophisticated CT-driven radiomics to prognosticate the mutation situation of KRAS in patients with colorectal cancer(CRC).Methods A total of 393 patients who underwent KRAS mutation testing and preoperative triphasic enhanced CT were analyzed retrospectively.All patients were divided into training group(n=276)and validation group(n=117)with a ratio of 7∶3.The characteristics tightly associated with KRAS mutation were extracted and screened to construct three models,include clinical,radiomics,and clinical-radiomics fusion models for prediction of KRAS mutation.The performance and clinical utility of these three models were assessed via receiver operating characteristic(ROC)curve and decision curve analysis(DCA).Results The study identified significant correlations between KRAS mutation and CEA,CA199,and a set of 13 radiomics features,respective-ly.Based on these clinical indicators and radiomics features,clinical,radiomics,and clinical-radiomics fusion models were constructed to prognosticate KRAS mutation.The radiomics model construc-ted in this study had good performance for the prediction of KRAS mutation status in CRC patients.Most notably,a clinical-radiomics nomogram that amalgamated both clinical risk factors and radiomics parameters emerged as the most effective predictor of KRAS mutation,with an area under the curve(AUC)of 0.782 and 0.744 in the training group and validation group,respectively.Conclusion The refined CT radiomics model serves as a robust,non-invasive,quantitative tool for the assessment of KRAS mutation status in CRC patients.

Objective ::To investigate the role of trehalose in hepatic ischemia-reperfusion injury and its underlying mechanisms.Methods:C57BL/6J mice were randomly divided into no-ischemia group, ischemia-reperfusion group, trehalose-treated group and normal saline control group. After ischemia for 90 minutes, reperfusion immediately or 6h, blood and liver tissues were collected, and serum was separated. The liver function parameters of ALT, AST, the inflammatory factors of TNF-α, IL-1β and IL-2, and the pathological changes of liver were detected to study the role of trehalose during hepatic ischemia-reperfusion injury. Hypoxia-reoxygenation cell model was established by AML12 mouse hepatocyte line, and divided into experimental group and control group. The experimental group was divided into low dose group and high dose group according to the concentration of trehalose administrated. And the control group had no use of trehalose. The level of apoptosis was measured to study the effect of trehalose on apoptosis induced by hepatic ischemia-reperfusion injury with flow cytometry. Western blot was utilized for detecting the levels of Caspase-3, Cleaved Caspase-3 and Bcl-2 protein to understand the molecular mechanisms of trehalose in apoptosis during hepatic ischemia-reperfusion injury.Results:In vivo animal experiments showed that liver function and such inflammatory factors as ALT, AST, TNF-α, IL-1β and IL-2 increased in ischemia-reperfusion group after hepatic ischemia-reperfusion ( P<0.05), and liver tissue became necrotic. After a treatment of trehalose, the levels of ALT, AST, TNF-α, IL-1β and IL-2 were lower than those of normalsaline control group and the area of liver tissue necrosis also decreased ( P<0.05). In vitro cell experiments showed that the apoptosis level of hepatocytes in the experimental group decreased compared with the control group.And the level of activated pro-apoptotic protein Cleaved Caspase-3 decreased, the level of anti-apoptotic protein Bcl-2 increased. Conclusions:Trehalose has protective effects on hepatic ischemia-reperfusion injury in vivo and in vitro. The mechanism may be involved in inhibiting inflammation induced by hepatic ischemia-reperfusion injury, suppressing the activation of Caspase-3 and promoting the expression of Bcl-2, thus played a protective role by extenuation of hepatocyteapoptosis.

Objective: To study subclinical hypothyroidism (SCH) with its treatment in patients after coronary artery bypass grafting (CABG). Methods: A total of 1500 patients received CABG by the same surgical team in our hospital from 2010-06 to 2014-03 were retrospectively studied. According to thyroid function, the patients were divided into 2 groups: SCH group,n=107 and Normal group, n=1393. With 1:4 propensity score matching, there were 104 patients in SCH group and 416 patients in Normal group enrolled in our research. The rates of intra-aortic balloom pumping (IABP) implantation and peri-operational blood transfusion, mechanical ventilation time, new onsets of stroke, myocardial infarction and atrial ifbrillation, malignant arrhythmia, acute kidney injury and in-hospital mortality were observed. The outcome of treatment was assessed by single- and multi-factor analysis. Results: Compared with Normal group, SCH group showed increased mechanical ventilation time (23.3±47.9) h vs (15.0±5.5) h, P<0.05; more patients had mechanical ventilation time>12 h (89.4% vs 78.8%),P<0.05 and more patients had IABP implantation (3.8% vs 0.72%),P<0.05. SCH was related to mechanical ventilation time>12 h (OR=2.363, 95% CI 1.183-4.516) and IABP implantation (OR=6.126, 95% CI 1.190-31.537). The in-hospital death and other events were similar between 2 groups,P>0.05. Conclusion: Our research indicated that SCH was related to mechanical ventilation time and IABP implantation in patients after CABG.

Objective To evaluate the effect of different sevoflurane postconditioning on myocardial injury in patients undergoing coronary artery bypass grafting (CABG ) with cardiopulmonary bypass (CPB ) .Methods Seventy-five NYHA class Ⅰ or Ⅱ patients ,aged 46-72 yr ,weighing 57-90 kg ,scheduled for elective CABG with CPB ,were randomly divided into 5 groups ( n=15 each) using a random number table :control group (groupⅠ) , postconditioning with continuous administration of 1.7% sevoflurane group (groupⅡ a ) , postconditioning with continuous administration of 3.4% sevoflurane group (group Ⅲa) ,postconditioning with interrupted administration of 1.7% sevoflurane group (Ⅱb) and postconditioning with interrupted administration of 3.4% sevoflurane group (group Ⅲb) .Sevoflurane was not given in group Ⅰ .In Ⅱa group ,after the anastomotic stomas of the internal mammary artery to anterior descending artery were released ,the patients continuously inhaled 1.7% sevoflurane for 15 min .In Ⅱb group ,after the anastomotic stomas were released .In Ⅲa group ,after the anastomotic stomas were released , the patients continuously inhaled 3.4% sevoflurane for 15 min , the patients inhaled 1.7%sevoflurane for 5 min first ,inhalation was interrupted for 5 min ,and then inhalation was recovered lasting for 5 min ,and it was 15 min in total .In Ⅲb group ,after the anastomotic stomas were released ,the patients inhaled 3.4% sevoflurane for 5 min first ,inhalation was interrupted for 5 min ,and then inhalation was recovered lasting for 5 min ,and it was 15 min in total .Venous blood samples were taken for determination of the plasma creatine kinase ,creatine kinase isoenzyme-MB , lactic dehydrogenase , and cardiac troponin I concentrations before CPB and at 6 and 24 h after operation .Myocardial specimens were obtained from the right auricle before CPB and after termination of CPB for microscopic examination of the ultrastructure .Results Compared with group Ⅰ , the concentration of cardiac troponin Ⅰ was significantly decreased at 6 and 24 h after operation ( P<0.05) ,and no significant changes were found in the other parameters in Ⅱb group ( P>0.05 ) .The pathological changes were significantly attenuated in sevoflurane postconditioning groups as compared with group Ⅰ ,especially in Ⅱb group . Conclusion Postconditioning with continuous administration of 3.4% sevoflurane for 15 min can attenuate myocardial damage in patients undergoing CABG with CPB .

Objective To evaluate the effect of gender and treatment strategy on remote ischemic preconditioning (RIPC)-induced reduction of myocardial damage in patients undergoing cardiac surgery.Methods We systematically searched the literature in PubMed,EMBase,and Cochrane Library (from Feb 1990 to Feb 2012) using the related keywords.Randomized control trials (RCTs) published in English with report on postoperative biomarkers of myocardial damage concerning RIPC-induced myocardial protection in adult patients undergoing cardiac surgery were included.Standardized mean difference (SMD) was calculated.Publication bias and sensitivity analysis were used to evaluate the reliability of overall enzymatic estimate.Meta-regression analysis was performed to explore the potential sources of significant heterogeneity among results of studies.Data were analyzed using Stata 12.0.Results Thirteen RCTs involving 985 patients were included in our study.Compared with controls,RIPC significantly reduced postoperative serum levels of biomarkers of myocardial damage with significant heterogeneity (SMD=-0.539; 95％CI:-0.926to-0.152; P＜0.05; I2 =88.7％,P＜0.01).No evidence of obvious publication bias was observed (P =0.083,Begg' s test; P =0.077,Egger' s test).Sensitivity analysis showed that each individual study produced no effect on the direction and magnitude of the overall effect size (P ＜ 0.05).Meta-regression analysis revealed that male (％) (coefficient =0.02 ; 95 ％ CI:-0.002-0.042 ; P =0.070 ; adjusted R2 =19.61％) and total ischemic time (min) (coefficient=-0.08; 95％CI:-0.154-0.002; P =0.055; adjusted R2 =19.47％) were the two major influential factors.Conclusion Gender affects RIPC-induced reduction of myocardial damage after cardiac surgery in patients,RIPC-induced reduction of myocardial damage infemale patients is superior to that in male patients and a better efficacy can be achieved by prolonging the single ischemic time or by increasing the ischemic cycles.

Objective To investigate the effects of sevoflurane postconditioning on myocardial ischemiareperfusion(I/R)injury in patients undergoing coronary artery bypass grafting(CABG)with cardiopulmonary bypass(CPB).Methods Forty NYHA Ⅰ -Ⅲ patients of both sexes,aged 55-64 yr,with BMI ＜ 30 kg/m2,scheduled for CABG under CPB,were randomly divided into 2 groups(n = 20): control group(group C)and sevoflurane postconditioning group(group S).Anesthesia was induced with midazolam and/or etomidate,fentanyl and rocuronium.Patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of propefol and intermittent iv injection of fentanyl and pipecuronium.In group S,2% sevoflurane was inhaled continuously for 15 min immediately after aortic unclamping.After anesthesia induction,before CPB,10 min after the end of CPB,at the end of operation,and 6 and 24 h after operation,MAP,HR,CVP,mean pulmonary arterial pressure,pulmonary arterial wedge pressure,CO and S(v)O2 were recorded,and CI,SVI,systemic vascular resistance index and pulmonary vascular resistance index were calculated.Blood samples were taken from central vein before aortic clamping,at 6 h of reperfusion and 24 h after operation for determination of plasma creatine kinase(CK),creatine kinase isoenzyme(CK- M B)and lactate dehydrogenase(LDH)activities and tropenin I(TnI)concentrations.Myocardial tissues were obtained from right auricle before aortic clamping and at the end of CPB for observation of the ultrastructure and the severity of myocardial injury was assessed.Results There was no significant difference in hemodynamics and parameters of cardiac function between the two groups(P ＞ 0.05).Compared with group C,plasma CK-MB and LDH activities at 6 h of reperfusion and plasma CK activity and TnI concentrations at 24 h after operation were significantly decreased and the myocardial injury was significantly reduced after the end of CPB in group S(P ＜ 0.05).Conclusion Sevoflurane postconditioning can protect myocardium against I/R injury induced by CPB in patients undergoing CABG.