OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.

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*

AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

Objective To explore the effects of lipoxygenase(LOX)on severe fever with thrombocytopenia syndrome virus(SFTSV)in human umbilical vein endothelial cells(HUVECs).Methods The CCK-8 assay was used to assess the cytotoxicity of LOX in HUVECs.Real-time quantitative PCR(qPCR)was adopted to detect the replication of viral RNA in cells.The infection rate of SFTSV to HUVECs was observed via indirect immunofluorescence assay(IFA).The expressions of intracellular viral NP protein and autophagy related proteins microtubule-associated protein 1 light chain 3(LC3)and adenosine 5'-monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)were detected via Western blotting.Lipid metabolomics was used to analyze the differences in expressions of intracellular metabolites in the SFTSV-infected Huh 7 with or without LOX treatment.Results The results of CCK-8 showed no obvious cytotoxicity to HUVECs with LOX≤8 mg/mL.With the increase of LOX concentrations,the viral RNA level,viral infection rate,and expressions of SFTSV nucleoprotein(NP)protein were gradually decreased,respectively.The autophagy reaction was activated in SFTSV-infected HUVECs,evidenced by the increased expression level of LC3 Ⅱ protein.Compared with the untreated group,LOX treatment resulted in decreased levels of LC3 Ⅱ and AMPK phosphorylation,and enhanced phosphorylation of mTOR in SFTSV-infected HUVEC.Conclusion LOX negatively regulates autophagy by inhibiting AMPK/mTOR signaling pathway,thereby inhibiting SFTSV replication.

Objective To construct a quality evaluation index system for training injury rehabilitation in military regional rehabilitation centers,so as to promote the systematization and standardization of quality management and provide references for the formulation of relevant policies.Methods The"structure-process-result"three-dimensional quality system model,literature analysis,semi-structured interview,and Delphi method were used to establish the index system,and its reliability and validity were tested.Results Twenty-two inquiry forms were distributed in two rounds of this study,and the effective recovery rates of the two rounds of expert correspondence were 100%.The authority coefficients(Cr)were 0.869 and 0.881,and the Kendall harmony coefficients were 0.230 and 0.339,respectively.The empirical verification showed good reliability and validity.The evaluation index system consisted of 3 primary indexes,12 secondary indexes and 48 tertiary indexes.Conclusion The index system is feasible,reliable and scientific,and can provide a practical and operable evaluation method for the rehabilitation quality management of training injuries.

Objective: To analyze the diagnostic and prognostic value of platelet aggregation rate in sepsis-related coagulation disorders. Methods: A total of 238 patients with sepsis were enrolled from Xinjiang Uygur Autonomous Region People's Hospital between June 2021 to June 2024. Patients were divided into coagulation dysfunction group (n=142) and non-dysfunction group (n=96) based on the occurrence of sepsis-related coagulation dysfunction. The general data, platelet aggregation rate and coagulation-related indicators of the two groups were compared. The 28-day survival outcomes were evaluated, and platelet aggregation rates were compared between survivors and non-survivor groups. Factors influencing the occurrence of sepsis-related coagulation dysfunction were analyzed. ROC curves were used to evaluate the predictive value of platelet aggregation rate for the prognosis of sepsis-related coagulation dysfunction. Results: Compared to the non-dysfunction group, APACHE II score, procalcitonin (PCT), activated partial thromboplastin time (APTT), platelet aggregation rate, and SOFA score were higher in the dysfunction group, while fibrinogen (Fib) was lower in the dysfunction group (P<0.05). The values were: (18.30±2.00) points vs (10.76±1.42) points, (7.27±2.10) ng/mL vs (3.87±1.62) ng/mL, (46.78±3.22) s vs (40.43±0.90) s, (69.07±6.32)% vs (55.78±2.96)%, (7.91±2.21) points vs (4.72±1.76) points, (243.23±40.91) mg/dL vs (342.09±46.58) mg/dL, respectively. The APTT、PCT level, platelet aggregation rate, APACHE II score and SOFA score were all risk factors for the development of sepsis-related coagulation dysfunction (OR>1, P<0.05). The platelet aggregation rate was higher in the non-survivor group compared to the survivor group (74.10±5.19 vs 66.05±4.87, P<0.05). The combination of platelet aggregation rate and PCT yielded the highest AUC for prediction, which was significantly greater than that of either single indicator (platelet aggregation rate: AUC=0.868; PCT: AUC=0.854, P<0.05). Conclusion: Platelet aggregation rate is an independent risk factor for the development of sepsis-associated coagulation dysfunction, and also an effective predictor for the prognosis of patients with sepsis coagulation dysfunction.

Objective: To investigate the distribution characteristics of Kidd blood group antigens, phenotypes and genotypes in Xinjiang and their influence on the risk of coronary heart disease. Methods: Samples from 7 981 patients treated at People's Hospital of Xinjiang Uygur Autonomous Region from August 1, 2023 to May 31, 2024 were collected for Jk(a-b-) phenotype screening via urea hemolysis test, followed by the third-generation sequencing (TGS). Kidd blood group Jk and Jk antigens in 1 081 patients with coronary heart disease and 1 021 healthy people were detected, and their phenotype frequency distribution was analyzed and corresponding gene frequencies were calculated. Correlation analysis and logistic regression were used to evaluate the influence of Kidd blood group antigen expression on coronary heart disease risk. Results: Two Jk(a-b-) phenotype samples were detected, both resulting from novel gene mutation combinations. Comparative analysis of two groups revealed a higher proportion of the Jk(a-b+) phenotype in the case group (22.5%, 243/1 081) than in the control group (18.5%, 189/1 021). Moreover, Kidd blood group phenotype distribution varied significantly across all ethnic groups in the case group (P<0.05). In the control group, the Hui ethnic group exhibited the highest JK JK genotype frequency 64.15% (34/53). In the case group, the highest JK allele frequency was observed in Mongol ethnic group 56.31% (125/222), and the lowest in Han patients 45.71% (341/746). The expression of Jk antigen was negatively correlated with coronary heart disease (P<0.05). Conclusion: The distribution of Kidd blood group system varied across ethnic groups in Xinjiang. The expression of Jk antigen may have protective effect on coronary heart disease, which provides a basis for future clinical blood transfusion treatment and the mechanism study of the correlation between Kidd blood group and coronary heart disease.

Objective To summarize the best evidence for diaphragm rehabilitation in mechanically ven-tilated ICU patients with ventilator-associated diaphragm dysfunction based on evidence-based methods.Meth-ods A systematic search was conducted across guideline websites,professional associations,and Chinese/English databases for evidence regarding diaphragm rehabilitation in mechanically ventilated ICU patients.The search timeframe spanned from database inception to December 31,2024.Two researchers independently per-formed quality assessment and synthesized the evidence.Results Twenty articles were included:2 clinical de-cisions,1 guideline,2 evidence summaries,3 systematic reviews,7 randomized controlled trials(RCT),and 5 expert consensuses/opinions.Twenty-seven pieces of evidence were formed across 6 themes:rehabilitation team,rehabilitation assessment,rehabilitation interventions,outcome evaluation,precautions,and education/training.Conclusion This study summarizes the best evidence for diaphragm rehabilitation in ICU mechani-cally ventilated patients.Healthcare professionals should implement diaphragm rehabilitation by integrating this evidence with specific clinical contexts to improve patient outcomes and enhance nursing quality.

Objective To analyze the diversity and composition of gut microbiota in individuals with circadian rhythm disruption and their correlation with cognition.Methods Night shift workers and regular shift workers were subjected from our hospital during August 2022 and October 2024.The participants with circadian rhythm disorders were assigned into an experimental group(n=24),and those with normal circadian rhythms were into a control group(n=24).Their height,weight,age,gender,body mass index(BMI)and fresh fecal samples were collected,and Montreal Cognitive Assessment(MoCA)and Mini-Mental State Examination(MMSE)were used to evaluate their mental status.Metagenomics,Alpha and Beta diversity analyses,Linear Discriminant Analysis Effect Size(LEfSe),and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to investigate the diversity and function characteristics of gut microbiota in the participants.Results There were no statistical differences between the 2 groups in baseline data,such as height,weight,gender,age,and BMI(P>0.05).Alpha diversity analysis indicated that no statistical differences were observed in the ACE,Chao1,Shannon,or Simpson indices between the 2 groups,while beta diversity analysis revealed significant differences(P<0.01),suggesting different structure of gut microbiota between them.In the experimental group,the abundance of Faecalibacterium prausnitzii and Agathobacter rectalis was decreased,while that of Escherichia coli and Phocaeicola vulgaratus was increased,with significant differences when compared with the control group(P<0.05).Additionally,KEGG functional analysis showed that the experimental group had obviously higher expression levels in Th17 cell differentiation and the IL-17 signaling pathway than the control group(P<0.05).Agathobacter rectalis and Faecalibacterium prausnitzii were positively correlated with MoCA score and MMSE score(P<0.05,P<0.01).Agathobacter rectalis was negatively correlated with the IL-17 signaling pathway and Th17 cell differentiation.Conclusion Individuals with circadian rhythm disorders have significant changes in the structure and function of gut microbiota when compared to those with normal circadian rhythms.Agathobacter rectalis may be involved in the regulation of the IL-17 signaling pathway and differentiation of Th17 cells,thereby possibly impacting the increases of cognitive score related to circadian rhythm disorders.