AIM: To investigate the differences in morphological structure and retinal blood perfusion between the affected eye and the contralateral healthy eye using optical coherence tomography angiography(OCTA)in patients with idiopathic macular epiretinal membrane(IMEM)before and after surgery, and to evaluate the association of these parameters with functional and anatomical outcomes to inform prognostic assessment. METHODS:A prospective study was conducted at Zhejiang Provincial People's Hospital between January 2023 and December 2024. Consecutive patients diagnosed with unilateral IMEM were enrolled; the fellow eye served as an internal control. All participants underwent standardized ophthalmic evaluations, including optical coherence tomography(OCT), OCTA, and color fundus photography. Key quantitative parameters assessed included best-corrected visual acuity(BCVA), central macular thickness(CMT), foveal avascular zone(FAZ)area, vessel density in the inner capillary plexus(ICP), superficial capillary plexus(SCP), deep capillary plexus(DCP), and choroidal capillary perfusion area(CCPA). Measurements were obtained preoperatively and at 1 and 3 mo postoperatively. Correlation analyses were performed between the above parameters and postoperative BCVA and CMT.RESULTS: This study enrolled 30 patients(60 eyes)diagnosed with IMEM, comprising 14 males and 16 females, with a mean age of 65.4±10.8 y.At baseline, IMEM-affected eyes demonstrated significantly reduced BCVA, DCP density, and FAZ area, alongside significantly increased CMT and CCPA, compared with contralateral controls. Following vitrectomy with membrane peeling, CMT decreased significantly at both 1 and 3 mo(both P<0.05)postoperatively; DCP density and BCVA showed significant improvement(both P<0.05). No significant change in FAZ area was observed postoperatively(P>0.05). At 3 mo postoperatively, BCVA of the affected eye was negatively correlated with CMT(r=-0.549, P=0.022). At 1 mo postoperatively, CMT was negatively correlated with preoperative DCP and FAZ, positively correlated with preoperative CMT, and positively correlated with ICP and SCP at 1 mo postoperatively, and negatively correlated with FAZ at 1 mo postoperatively(all P<0.05). Furthermore, CMT at 3 mo postoperatively was negatively correlated with preoperative DCP(r=-0.498,P=0.042).CONCLUSION:In patients with IMEM, the affected eyes exhibit significantly reduced DCP density and FAZ area, alongside increased CMT and CCPA. Following vitrectomy with membrane peeling, CMT decreased progressively, DCP density demonstrated partial restoration, and vision improved gradually. Preoperatively, smaller CMT larger DCP, and FAZ were associated with more favorable surgical outcomes; postoperatively, smaller ICP and SCP densities—combined with a larger FAZ—also correlated with better functional recovery.

ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

ObjectiveTo evaluate the application effect of morphology driven preparation technique in indirect restoration of posterior teeth. Methods84 patients with dental defects were selected and divided into the control group and the experimental group randomly， with 42 patients in each group （a total of 84 teeth）. Traditional preparation and morphology driven preparation techniques were used to complete dental preparation and adhesive glass ceramic restorations， respectively. The satisfaction， masticatory function， World Dental Federation （FDI） Scores for edge fracture and fixation，edge adaptability index，periodontal bleeding index （BI） and plaque index （PLI） of the two groups of patients were evaluated and various indicator data were recorded and statistically analyzed at 3 and 6 months after restoration completion. ResultsThere was no statistically significant difference in satisfaction between the two groups after 3 and 6 months of repair； Both groups of data showed a significant improvement in masticatory function. There was no statistical difference after 3 and 6 months of repair. However， a statistically significant difference in masticatory function was noted after 6 months of repair compared with before and after 3 months of repair. As the repair time increased， the masticatory effect improved significantly. There was no statistically significant difference in the edge fracture and fixation index between the two groups at 3 months after repair， but there was a statistically significant difference between the two groups at 6 months with the experimental group outperforming the control group（P<0.05）. The edge adaptability， BI， and PLI index were statistically significant between the two groups after 3 and 6 months of repair and the experimental group had a significant advantage （P<0.05）. ConclusionBoth types of tooth preparation techniques can improve patient masticatory function and reach high satisfaction after repair. However， morphology driven preparation technique has significant advantages in edge adaptability， edge fracture and fixation index scores and improve periodontal conditions. This technique is an effective method for improving dental preparation in adhesive indirect restoration of posterior teeth.

ObjectiveTo investigate the efficacy and safety of Shuganning injection in the treatment of liver injury by observing the clinical outcome of patients with liver injury after treatment with Shuganning injection and comparing it with reduced glutathione （GSH）. MethodsThis study was conducted among 175 patients with liver injury who attended 6 hospitals in China （Beijing YouAn Hospital， Capital Medical University； Nanyang First People’s Hospital； The Second Affiliated Hospital of Xi’an Jiaotong University； The Fifth Medical Center of Chinese PLA General Hospital； The Third Hospital of Hebei Medical University； The Affiliated Hospital of Guizhou Medical University） from April 25， 2019 to February 28， 2022. The patients were divided into experimental group （89 patients treated with Shuganning injection） and control group （86 patients treated with GSH）， and the course of treatment was 4 weeks for both groups. Related indicators were recorded before treatment， after treatment， and after drug withdrawal for 8 weeks， including liver function parameters， blood biochemical parameters， blood lipids， coagulation profiles， liver fibrosis markers， traditional Chinese medicine （TCM） syndrome score， and ultrasound findings， as well as adverse events during treatment. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Wilcoxon signed-rank test was used for comparison of observation indicators before treatment， at week 4 of treatment， and after drug withdrawal for 8 weeks. When the efficacy evaluation of TCM syndromes was used as the outcome， a pooled analysis was performed for the effective cases and the markedly effective cases， and a Logistic regression model was used to calculate the odds ratio （OR） and its 95%CI. ResultsAfter 4 weeks of treatment with Shuganning injection， the patients showed significant reductions in TCM syndrome score （P<0.001） and the levels of aspartate aminotransferase， alanine aminotransferase， total bilirubin， and direct bilirubin （all P<0.001） and a significant increase in the level of albumin （P=0.002）， and these significant improvements persisted after drug withdrawal for 8 weeks. Furthermore， compared with the control group， the experimental group had a significantly higher proportion of patients assessed as effective or markedly effective cases （48.31% vs 32.56%， P=0.033）. Compared with the control group， the experimental group had a significantly greater change in TCM syndrome score at weeks 1-4 of treatment and after drug withdrawal for 8 weeks （P<0.05）. At week 4 of treatment， the experimental group had a significantly greater reduction in alanine aminotransferase than the control group （P<0.05）， and at week 8 after drug withdrawal， the experimental group had a significantly greater reduction in alanine aminotransferase and aspartate aminotransferase than the control group （all P<0.05）. One patient in the experimental group （1.12%） experienced an adverse event， which was determined to be associated with the progression of viral hepatitis. ConclusionShuganning injection can effectively improve liver injury， with good long-term efficacy and a low incidence rate of adverse reactions.

ObjectiveTo identify the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the health check-up population， and to perform stratified management of patients with the low， medium， and high risk of advanced fibrosis based on noninvasive fibrosis scores. MethodsA cross-sectional study was conducted among 3 125 individuals who underwent physical examination in Beijing Physical Examination Center from December 2017 to December 2019， and they were divided into MAFLD group with 1 068 individuals and non-MAFLD group with 2 057 individuals. According to BMI， the MAFLD group was further divided into lean MAFLD group （125 individuals with BMI<24 kg/m²） and non-lean MAFLD group （943 individuals with BMI≥24 kg/m²）. Indicators including demographic data， past history， laboratory examination， and liver ultrasound were compared between groups. Fibrosis-4 （FIB-4） score， NAFLD fibrosis score （NFS）， aspartate aminotransferase-to-platelet ratio index （APRI）， and BARD score were calculated for the patients in the MAFLD group to assess the risk of advanced fibrosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influence of each indicator in MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-9.758， P<0.05）， proportion of male patients （χ²=137.555， P<0.05）， and levels of body weight （Z=-27.987， P<0.05）， BMI （Z=-32.714， P<0.05）， waist circumference （Z=-31.805， P<0.05）， hip circumference （Z=-26.342， P<0.05）， waist-hip ratio （Z=-28.554， P<0.05）， alanine aminotransferase （ALT） （Z=-25.820， P<0.05）， aspartate aminotransferase （AST） （Z=-16.894， P<0.05）， gamma-glutamyl transpeptidase （GGT） （Z=-25.069， P<0.05）， alkaline phosphatase （Z=-12.533， P<0.05）， triglyceride （Z=-27.559）， total cholesterol （Z=-7.833， P<0.05）， low-density lipoprotein cholesterol （LDL-C） （Z=-8.222， P<0.05）， and uric acid （UA） （Z=-20.024， P<0.05）， as well as a significantly higher proportion of patients with metabolic syndrome （MetS） （χ²=578.220， P<0.05）， significantly higher prevalence rates of hypertension （χ²=241.694， P<0.05）， type 2 diabetes （χ²=796.484， P<0.05）， and dyslipidemia （χ²=369.843， P<0.05）， and a significant reduction in high-density lipoprotein cholesterol （HDL-C） （Z=23.153， P<0.001）. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=1.45， 95% confidence interval ［CI］： 1.203‍ ‍—‍ ‍1.737）， ALT （OR=1.05， 95%CI： 1.046‍ ‍—‍ ‍1.062）， LDL-C （OR=1.23， 95%CI： 1.102‍ ‍—‍ ‍1.373）， and comorbidity with MetS （OR=5.97， 95%CI： 4.876‍ ‍—‍ ‍7.316） were independently associated with MAFLD. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.736， P<0.05） and HDL-C （Z=2.679， P<0.05） and significant reductions in the proportion of male patients （χ²=28.970， P<0.05）， body weight （Z=-14.230， P<0.05）， BMI （Z=-18.188， P<0.05）， waist circumference （Z=-13.451， P<0.05）， hip circumference （Z=-13.317， P<0.05）， ALT （Z=-4.519， P<0.05）， AST （Z=-2.258， P<0.05）， GGT （Z=-4.592， P<0.05）， UA （Z=-4.415， P<0.05）， the proportion of patients with moderate or severe fatty liver disease or MetS （χ²=42.564， P<0.05）， and the prevalence rates of hypertension （χ²=12.057， P<0.05） and type 2 diabetes （χ²=3.174， P<0.05）. Among the patients with MAFLD， 10 patients （0.9%） had an FIB-4 score of >2.67， 4 patients （0.4%） had an NFS score of >0.676， 8 patients （0.7%） had an APRI of >1， and 551 patients （51.6%） had a BARD score of ≥2. ConclusionThere is a relatively high prevalence rate of MAFLD among the health check-up population in Beijing， but with a relatively low number of patients with a high risk of advanced fibrosis， and such patients need to be referred to specialized hospitals for liver diseases.

ObjectiveTo screen for the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the physical examination population， to observe the characteristics of MAFLD patients， and to compare the differences in lifestyle between the MAFLD population and the non-MAFLD population. MethodsA cross-sectional study was conducted among 6 206 individuals who underwent physical examination in a physical examination institution in Beijing from December 2015 to December 2019， and according to the new diagnostic criteria for MAFLD， the examination population was divided into MAFLD group and non-MAFLD group. Based on body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<24 kg/m²） and non-lean MAFLD group （BMI ≥24 kg/m²）. Related data were compared between groups， including demographic indicators， education level， work pressure， physical measurement indicators， and lifestyles such as sleep， diet， and exercise. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsOf all individuals in this study， 1 926 （31.1%） had MAFLD and 4 280 （68.9%） did not have MAFLD. Compared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-14.459， P<0.001）， proportion of male patients （χ²=72.004， P<0.001）， work pressure （χ²=7.744， P=0.005）， body weight （Z=-43.508， P<0.001）， BMI （Z=-47.621， P<0.001）， waist circumference （Z=-48.515， P<0.001）， hip circumference （Z=-42.121， P<0.001）， and waist-hip ratio （Z=-43.535， P<0.001）， as well as a significantly lower education level （χ²=33.583， P<0.001）. In terms of behavior， the MAFLD group had a significantly shorter sleep time （χ²=5.820， P=0.016） and a significantly faster eating speed （χ²=74.476， P<0.001）. In terms of diet， the patients in the MAFLD group consumed more high-sodium， high-sugar， and high-calorie diets （χ²=42.667， P<0.001） and low-fiber diet （χ²=4.367， P=0.008）. In terms of exercise， the MAFLD group had a significantly higher proportion of patients without exercise habits （χ²=10.278， P=0.001）. Further analysis showed that there were 202 individuals （10.5%） in the lean MAFLD group and 1 724 （89.5%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.368， P=0.001） and education level （χ²=9.647， P=0.002） and significantly lower proportion of male patients （χ²=27.664， P<0.001）， body weight （Z=-18.483， P<0.001）， BMI （Z=-23.286， P<0.001）， waist circumference （Z=-18.565， P<0.001）， and hip circumference （Z=-18.097， P<0.001）， and in terms of behavior， the non-lean MAFLD group had a significantly faster eating speed （χ²=4.549， P=0.033）. ConclusionThere is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing， with a higher number of people with unhealthy lifestyles compared with the non-MAFLD population.

Objective To investigate the clinical and metabolic factors associated with the development and regression of metabolic dysfunction-associated fatty liver disease(MAFLD)in the physical examination population.Methods A retrospective observational study was conducted on 6 809 individuals who underwent physical examination in a physical examination institution in Beijing from December 2013 to December 2019,with a mean follow-up time of 52.1±13.5 months.According to the new diagnostic criteria for MAFLD,these individuals were divided into MAFLD group and non-MAFLD group,and the two groups were compared in terms of demographic indicators,body measurement indicators,and laboratory indicators at the first(baseline)and last physical examinations.The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data.A Logistic regression analysis was used to investigate the impact of various observation indicators on the development and regression of MAFLD.Results In this study,there were 4 533 individuals(66.6%)in the non-MAFLD group at baseline,among whom 15.6%developed MAFLD at the last physical examination.Compared with the non-MAFLD population,the MAFLD population had significantly higher age(Z=-6.739),number of male patients(χ2=178.534),body weight(Z=-22.302),body mass index(BMI)(Z=-22.818),waist circumference(Z=-23.117),hip circumference(Z=-18.446),systolic blood pressure(SBP)(Z=-13.301),diastolic blood pressure(DBP)(Z=-13.491),fasting blood glucose(FBG)(Z=-11.787),triglyceride(TG)(Z=-16.623),low-density lipoprotein cholesterol(LDL-C)(Z=-10.256),alanine aminotransferase(ALT)(Z=-14.250),aspartate aminotransferase(AST)(Z=-7.481),and proportion of patients with metabolic syndrome(MetS)at baseline(χ2=185.283),and there were more patients with increases in body weight,waist circumference,hip circumference,TG,TC,ALT,and AST at the final physical examination(all P<0.05);these patients had a lower level of HDL-C at baseline(Z=15.416),and there were more patients with a reduction at the last physical examination(P<0.05).There were 2 276 individuals(33.4%)in the MAFLD group at baseline,among whom 23.8%showed regression of MAFLD at the last physical examination.Compared with the population without regression of MAFLD,the population with regression of MAFLD had a significantly younger age(Z=2.185),a significantly higher number of female patients(χ2=0.340),significantly lower levels of body weight(Z=-8.909),BMI(Z=-10.205),waist circumference(Z=-11.183),hip circumference(Z=-7.178),SBP(Z=-3.627),DBP(Z=-3.443),TG(Z=-5.945),ALT(Z=-9.664),and AST(Z=-5.904),and a significantly lower proportion of patients with MetS(χ2=42.082),and there were more patients with reductions in body weight,waist circumference,hip circumference,blood pressure,TG,TC,ALT,and AST at the final physical examination(all P<0.05);these patients had a higher level of HDL-C at baseline(Z=6.778),and there were more patients with an increase at the last physical examination(P<0.05).The multivariate Logistic regression analysis showed that sex and changes in body weight and HDL-C during physical examination were independently associated with the development and regression of MAFLD(all P<0.05).Conclusion There is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing,with a higher proportion of male patients.There are significant metabolic disorders and liver function abnormalities,and changes in body weight and HDL-C are the most important predictive indicators for the development and regression of MAFLD.

Objective:To investigate the clinical efficacy of acupuncture aimed at awakening the mind and opening the orifices, when combined with a qi-tonifying and blood-circulating decoction, in the treatment of post-stroke dysphagia due to qi deficiency and blood stasis. Methods:A randomized controlled study was conducted involving 86 patients with post-stroke dysphagia due to qi deficiency and blood stasis who were admitted to the Department of Acupuncture and Moxibustion at Yan'an Hospital of Traditional Chinese Medicine from January 2020 to March 2023. The patients were randomly divided into a control group and a treatment group, with 43 cases in each group, using a random number table method. The control group received conventional treatment, while the treatment group received acupuncture aimed at awakening the mind and opening the orifices combined with a qi-tonifying and blood-circulating decoction. Both groups were treated for 1 month. Clinical efficacy, swallowing function, serological indicators, floating index, and quality of life were compared between the two groups. Results:After treatment, the Standardized Swallowing Assessment score in the treatment group was (18.23 ± 2.04) points, which was significantly lower than that in the control group [(22.52 ± 4.38) points, t = 5.82, P < 0.05]. The Water-Swallowing test score in the treatment group was (2.77 ± 0.55) points, which was significantly higher than that in the control group [(2.00 ± 0.42) points, t = 7.30, P < 0.05]. The level of superoxide dismutase in the treatment group was (147.54 ± 21.03) kU/L, which was significantly higher than that in the control group [(128.31 ± 18.54) kU/L, t = 4.50, P < 0.05]. The Pulsatility Index in the treatment group was (0.72 ± 0.25), which was significantly lower than that in the control group [(0.83 ± 0.24), t = 0.74, P < 0.05]. The cerebral vascular reserve in the treatment group was (42.28 ± 5.69)%, which was significantly higher than that in the control group [(35.45 ± 4.31)%, t = 2.03, P < 0.05]. The Swallowing Quality-of-Life Questionnaire score in the treatment group was (76.33 ± 11.54) points, which was significantly higher than that in the control group [(68.02 ± 12.16) points, t = 3.25, P < 0.05]. The response rate in the treatment group was 97.67% (42/43), which was significantly higher than that in the control group [86.05% (37/43), χ2 = 3.89, P < 0.05]. Conclusions:The use of acupuncture for awakening the mind and opening the orifices, combined with a qi-tonifying and blood-circulating decoction, can significantly enhance clinical efficacy and improve the quality of life for patients with post-stroke dysphagia due to qi deficiency and blood stasis syndrome compared with conventional treatment.

Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Objective To explore the role and mechanism of ferroptosis in vitamin D3(VD3)improving the cytotoxicity of keratinocytes(HaCaT cells)induced by nitrogen mustard(NM).Methods HaCaT cells were treated with gradient concentrations of NM(5,10,20,and 50 μmol/L)alone or in combination with ferroptosis inhibitor ferrostatin-1 or liproxstatin-1(10 μmol/L),Nrf2-specific agonist tBHQ(10 μmol/L),and VD3(10 nmol/L),respectively.After co-culture for 24 h,cell viability was assessed,and the intracellular contents of glutathione(GSH)and malondialdehyde(MDA)were measured.Additionally,the expression levels of Nrf2,xCT,and GPX4 were detected.Results NM exerted inhibitory effect on the proliferation of HaCaT cells in a dose-dependent manner,and the cell viability was reduced to approximately 55%at an NM concentration of 20 μmol/L(P<0.05).Ferroptosis inhibitors significantly mitigated the cytotoxic damage induced by NM in HaCaT cells(P<0.05),but activation of nuclear factor E2 related factor 2(Nrf2)markedly attenuated NM-induced ferroptosis,as indicated by the restoration of intracellular GSH level and the decrease in MDA content(P<0.05).VD3 specifically targeted the Nrf2 signaling pathway,upregulated the expression of xCT and GPX4 protein,thereby inhibiting ferroptosis and reducing NM-induced cytotoxicity in HaCaT cells.Conclusion VD3 mitigates NM-induced cytotoxicity in HaCaT cells by inhibiting ferroptosis via Nrf2 activation.