OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf （PL） extract against ferroptosis induced by H2O2 in IEC-6 cells. METHODS Using IEC-6 cells as object， the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated； IEC-6 cells were divided into control group， H2O2 group， H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group. The levels of oxidant stress indexes [content of malondialdehyde （MDA）， activity of superoxide dismutase （SOD）， and levels of reactive oxygen species （ROS）]， mitochondrial membrane potential （MMP） as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NADPH/quinone oxidoreductase-1 （NQO-1）， cystine/glutamate anti-porter （xCT）， glutathione peroxidase 4 （GPX4） and ferritin heavy chain （FTH） were detected. RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells （P＜ 0.01）. Compared with the control group， MDA content， ROS level， mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly， while SOD activity， MMP， mRNA expressions of xCT， GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly （P＜0.01 or P＜0.05）. Compared with the H2O2 group， oxidative stress Δ indexes of H2O2+PL 25， 50 μg/mL groups were reversed to different extents， MMP level was increased significantly， as well as mRNA and protein expressions of Nrf2， HO-1， NQO-1，xCT， GPX4 and FTH were up-regulated to different extents；there were statistical significances in some indexes between groups （P＜0.01 or P＜0.05）. CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2， which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.

ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

BACKGROUND:Post and core restoration is a common choice for tooth defects,but the repair effects of various post and core materials are different. OBJECTIVE:To evaluate the stress distribution at the post and core,tooth root,and bonding agent site of post and core models made of different elastic modulus post and core materials using finite element method. METHODS:A three-dimensional root canal treated maxillary central incisor model was built using three-dimensional modeling software,which was restored with a full ceramic crown.The post and core materials in the restoration used nanoceramic resin(elastic modulus=12.8 GPa),composite resin(elastic modulus=16 GPa),hybrid ceramic(elastic modulus=34.7 GPa),glass ceramic(elastic modulus=95 GPa),titanium alloy(elastic modulus=112 GPa),and zirconia(elastic modulus=209.3 GPa).The model was fixed in cortical bone.A 100 N concentrated force of 45° from the long axis of the tooth was applied to 1/3 of the crown and tongue side of the central incisor.The stress distribution of the post and core,dentin,and tooth-root bonding agent in the model was repaired by the maximum principal stress criterion. RESULTS AND CONCLUSION:(1)When the post and core materials with higher elastic modulus was used,the post-core stress in the repair model was more concentrated.When the elastic modulus of the post and core materials(nanoceramic resin and composite resin)was close to dentin,the stress distribution of the post and core was more uniform.The stress distribution of dentin in all restoration models was similar regardless of post and core materials.When the post and core with higher elastic modulus was used,more stress concentration was shown at the post and root bonding agent in the repair model.(2)The maximum stress values at the post and core,tooth root,and the bonding agent site of post and tooth root in the nanoceramic resin model were 31.00,33.21,and 0.51 MPa,respectively.The maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root in the composite resin model were 36.84,33.14,and 0.59 MPa,respectively.In the mixed ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 64.05,32.83,and 1.00 MPa,respectively.In the glass ceramic model,the maximum stress values at the post and core,tooth root,and the bonding agent between the post and tooth root were 112.30,32.69,and 1.73 MPa,respectively.In the titanium alloy model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 120.00,32.17,and 1.86 MPa,respectively.In the zirconia model,the maximum stress values of the post and core,tooth root,and the bonding agent between the post and tooth root were 148.80,31.85,and 2.28 MPa,respectively.(3)The higher the elastic modulus of the post and core material,the higher the maximum stress at the post and core during restoration.The elastic modulus of the post and core material had no significant effect on the maximum stress of the dental bonding agent and dentin.

Objective:To explore the clinical efficacy of areola approach endoscopic thyroidectomy (AET) and gasless axillary approach endoscopic thyroidectomy (GAET) in the treatment of papillary thyroid carcinoma (PTC) patients.Methods:A total of 96 PTC patients from the Thyroid Surgery Department of Linyi People’s Hospital from May. 2019 to May. 2022 were selected and randomly divided into 48 patients using a random number table method. The areola group received AET, while the armpit group received GAET. The surgical situation, postoperative recovery, relevant biochemical indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), parathyroid hormone (PTH), blood calcium] before and after surgery, postoperative pain level, discomfort level, neck function, and complications were compared between the two groups.Results:The surgical time and extubation time of the armpit group were (125.71±15.73) minutes and (3.12±0.53) days, respectively, which were shorter than those of the areola group (137.94±20.02) minutes and (3.48±0.46) days. The intraoperative bleeding volume was (14.19±4.16) mL, which was less than that of the areola group (22.65±7.39) mL, and the number of lymph nodes cleaned was 5.06±1.02, which was more than that of the areola group (4.23±1.14) ( P<0.05) ; there was no significant difference in postoperative drainage volume and hospital stay between the two groups ( P>0.05) ; Peripheral blood WBC in the armpit group on the 1st and 3rd day after surgery [ (5.69±0.15) ×10 9/L, (5.52±0.14) ] ×10 9/L, ESR [ (8.21±0.55) mm/h, (7.64±0.60) mm/h], CRP [ (10.06±1.78) ng/L, (8.93±1.33) ng/L] were lower than those in the areola group [ (5.83±0.21) ×10 9/L, (5.70±0.23) ×10 9/L, (8.87±0.74) mm/h, (8.19±0.68) mm/h, (12.45±1.90) ng/L, (10.45±1.50) ng/L] ( P<0.05). There was no significant difference in the levels of the above biochemical indicators 5 days after surgery ( P>0.05). There was no significant difference in peripheral blood PTH and calcium levels between the two groups on the 1st, 3rd, and 5th postoperative days ( P>0.05). The pain level [ (3.25±0.32) scores, (2.53±0.27) scores, (1.82±0.22) scores] and discomfort level [ (6.85±0.71) scores, (5.24±0.66) scores, (3.51±0.57) scores] in the axillary group were lower than those in the areola group [ (3.78±0.40) scores, (2.89±0.34) scores, (2.06±0.26) scores, (7.46±0.84) scores, (6.09±0.73) scores, (4.16±0.60) scores] on the 1st, 3rd, and 5th postoperative days ( P<0.05). The neck flexion, lateral flexion, and extension range of motion in the axillary group on the 3rd day after surgery were (33.16±3.09) °, (27.63±2.57) °, and (30.44 2.73) °, respectively, which were greater than those in the areola group[ (30.08±2.76) °, (25.14±2.30) °, and (27.98±2.54) °], and the swallowing disorder index was (30.16±4.97) points lower than the (34.83±4.13) points in the areola group ( P<0.05). The incidence of complications in the axillary group was 4.17% (2/48), lower than the 16.67% (8/48) in the areola group. Conclusion:GAET treatment for PTC patients can improve the effect of lymph node dissection, reduce the degree of surgical trauma, postoperative pain and discomfort, accelerate early postoperative recovery of neck function, and reduce complications.

BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P＜0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P＜0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.

Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.

Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective:To observe the clinical efficacy of plan-do-check-Act(PDCA)cycle management model combined with pulsed tooth punch applied in maintenance period of the patients with moderate to severe periodontitis,and to provide the theoretical basis for application of the PDCA cycle management model in the periodontitis patients.Methods:A total of 50 patients with moderate to severe periodontitis were selected based on predefined inclusion,exclusion,and elimination criteria.The patients were randomly divided into experiment group(n=25)and control group(n=25).The patients in experiment group underwent maintenance care with pulsed tooth punch in combination with the BASS brushing technique,while the patients in control group maintained oral hygiene with the BASS brushing technique alone.The patients in both two groups were managed with the PDCA cycle management model.The patients were asked to return for follow-up visits at 2,4,8,and 12 weeks of self-care,and the personalized corrections and guidance were provided based on the plaque accumulation.The clinical periodontal parameters,including plaque index(PLI),probing depth(PD),and bleeding index(BI),at 4 and 12 weeks of self-care,as well as the levels of tumor necrosis factor-α(TNF-α)and interleukin-17(IL-17)in the gingival crevicular fluid of the patients in two groups were observed and recorded.Results:After 4 and 12 weeks of self-care,compared with control group,the PLI,PD,and BI of the patients in experiment group were significantly decreased(P<0.01);compared with baseline,the PLI,PD,and BI of the patients in both two groups at 4 and 12 weeks of self-care were increased(P<0.05 or P<0.01);Compared with 4 weeks of self-care,the PLI,PD,and BI of the patients at 12 weeks of self-care were increased(P<0.01).After 4 and 12 weeks of self-care,compared with control group,the levels of TNF-α and IL-17 in gingival crevicular fluid of the patients in experiment group were significantly decreased(P<0.01);compared with baseline,the levels of TNF-α and IL-17 in gingival crevicular fluid of the patients in two groups at 4 and 12 weeks of self-care were increased(P<0.01).Conclusion:The use of pulsed tooth punch under the PDCA cycle management model can significantly decrease the PLI,PD,BI,and the levels of inflammatory factors in gingival crevicular fluid of the patients with moderate to severe periodontitis,and inhibit the plaque formation and control the gingival inflammation,benefite the maintenance of efficacy of the patients with moderate to severe periodontitis.

Objective To study the effect of neuromodulatory protein-1(NRG-1)in inhibiting sepsis induced myocardial injury and its mechanism.Methods The rat sepsis model was established by cecal ligation and puncture(CLP).SD rats were divided into the sham operation group,sepsis group,sepsis+NRG group(rhNRG,10 μg/kg).After 12,24 h of successful modeling,the heart and peripheral serum of the surviving rats in each group were taken respectively.The HE staining was used to observe the changes of cardiac tissue morphology and structure,and ELISA was used to detect the expression levels of creatine kinase(CK),crea-tine kinase MB isoenzyme(CK-MB),sensitive troponin Ⅰ(cTnⅠ)in serum,tumor necrosis factor-α(TNF-α)in cardiac tissue and IL-6 expression level;Western blot was used to detect the phosphorylation protein ki-nase B(p-Akt),phosphorylation glycogen synthase kinaseβ(p-GSK3β),B-cell lymphoma/leukemia-2(Bcl-2)and Bax protein expression in rat myocardial tissue.Results After 12,24 h of modeling,compared with the sham group,the expression levels of CK,CK-MB and cTnⅠ in serum,TNF-α,IL-6 and Bax protein in myocar-dial tissue in the sepsis group all were significantly increased(P＜0.05),while the expression levels of p-Akt and p-GSK3β in myocardial tissue were significantly decreased(P＜0.05).After 12,24 h of modeling,com-pared with the sepsis group,the expression levels of CK,CK-MB,cTn Ⅰ in the serum and the expression levels of TNF-α,IL-6 in the myocardial tissue of the sepsis+NRG group were significantly decreased;after 24 h of modeling,compared with the sepsis group,the expression level of Bax protein in myocardial tissue of the sep-sis+NRG group was decreased,while the p-Akt,p-GSK3β expression levels were increased(P＜0.05).The pathological results showed that compared with the sham operation group,the sepsis group produced signifi-cant lesions;compared with the sepsis group,the lesions in the sepsis+NRG group were alleviated.Conclusion The expression levels of related biomarkers in septic myocardial injury have change.NRG-1 could improve the cardiac function through Akt/GSK3β pathway,inhibit the related proinflammatory factors and reduce the myocardial tissue damage.