Objective: To investigate factors influencing perioperative blood transfusion in patients with scarred uterus during pregnancy undergoing cesarean section, construct and validate a transfusion risk prediction model, and provide evidence for preoperative assessment and blood management. Methods: Clinical data of 405 patients undergoing cesarean section for scarred uterus during pregnancy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to December 2024 were retrospectively collected. The dataset was randomly divided into a training set (n=284) and a validation set (n=121) at a 7∶3 ratio. Within the training set, Firth-penalized logistic regression was employed for multivariate analysis to identify independent factors influencing perioperative blood transfusion and construct a predictive model. Model performance was evaluated in the validation set. Results: Multivariate Firth regression analysis showed that severe placenta previa (OR=75.566, 95%CI: 8.603-9979.174) and placenta accreta (OR=4.591, 95%CI: 1.120-19.416) were independent risk factors for perioperative blood transfusion, while preoperative red blood cell count (OR=0.189, 95%CI: 0.083-0.405) and fibrinogen levels (OR=0.588, 95%CI: 0.395-0.855) were protective factors. The predictive model constructed based on these four variables demonstrated good discriminatory performance, with areas under the receiver operating characteristic curves of 0.803 (95%CI: 0.740-0.867) and 0.753 (95%CI: 0.644-0.862) in the training and validation sets, respectively. Conclusion: For patients with scarred uterus during pregnancy undergoing cesarean section, severe placenta previa and placenta accreta significantly increase the risk of transfusion, while higher preoperative red blood cell count and fibrinogen levels exert a protective effect. The predictive model established in this study facilitates the identification of patients requiring transfusion, thereby enabling preoperative blood preparation and optimized blood management.

Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.There-fore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural com-pounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehen-sive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Objectives:This study aims to explore the value of the baseline extracellular volume(ECV)measured by cardiac magnetic resonance(CMR)in predicting cardiac response in patients with light chain cardiac amyloidosis(AL-CA)after treatment.Methods:This single-center retrospective cohort study included AL-CA patients diagnosed between May 2020 and March 2023.Baseline ECV measurement and other relevant parameters were derived from CMR.Therapeutic cardiac response was assessed through serial measurements of N-terminal pro-B-type natriuretic peptide(NT-proBNP).Complete recovery was defined as achieving NT-proBNP≤350 pg/ml post-treatment.Patients demonstrating>60%reduction from baseline NT-proBNP without attaining complete response criteria were classified as very good partial recovery.Those showing 31%-60%decreases from baseline NT-proBNP without meeting the threshold for very good partial recovery were qualified as partial recovery,while≤30%reductions from baseline were considered as non-recovery.The study evaluated two endpoints:the initial emergence of any cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery)and the subsequent attainment of optimal cardiac recovery(encompassing partial recovery,very good partial recovery,or complete recovery).The patients were divided into two groups based on whether they experienced cardiac recovery at the end of follow-up:the recovery group(n=24,comprising 7 with partial recovery,14 with very good partial recovery,and 3 with complete recovery)and the non-recovery group(n=16).Cox Proportional hazards regression models were used to analyse the impact of baseline ECV on the cardiac recovery.The Kaplan-Meier method and log-rank test were used to assess and compare the probability and timing of cardiac recovery between different baseline ECV groups.Results:Among the 40 patients,28(70%)were male,with a mean age of(58?±?8)years.32 patients(80%)had the λ subtype of AL-CA.During a median follow-up of 568(155,1 049)days,15 patients showed partial cardiac recovery at 60 days post-treatment,and 3 patients achieved very good partial cardiac recovery;by 720 days of treatment and until the end of follow-up,3 patients achieved complete cardiac recovery.Multivariate Cox regression analysis revealed that baseline ECV(HR=0.937,95%CI:0.879-0.999,P=0.045)and daratumumab-based regimens(HR=3.279,95%CI:1.098-9.796,P=0.033)were significant predictors of the initial cardiac recovery.Similarly,baseline ECV(HR=0.931,95%CI:0.867-1.000,P=0.048)and daratumumab-based regimens(HR=3.132,95%CI:1.052-9.319,P=0.040)were also independent predictors for the best cardiac recovery.Kaplan-Meier analysis demonstrated that patients with baseline ECV<54%achieved an earlier first cardiac recovery than those with baseline ECV≥54%(log-rank P=0.014)and the group with baseline ECV<55%were more likely to achieve the best cardiac recovery compared to those with baseline ECV≥55%(log-rank P=0.006).Conclusions:Baseline ECV measured by CMR can serve as an independent predictor of cardiac recovery in AL-CA patients after treatment.Lower baseline ECV levels are associated with a faster and more favorable cardiac recovery.The daratumumab-based regimens demonstrated superior cardiac recovery outcomes.

Objectives:To investigate the clinical value of cardiac magnetic resonance imaging(CMR)feature-tracking strain analysis in risk stratification of diabetic heart failure with preserved ejection fraction(HFpEF).Methods:In this retrospective study,a total of 215 patients with diabetic HFpEF who underwent CMR at Chinese Academy of Medical Sciences Fuwai Hospital from January 2012 to December 2018 were included.Myocardial strain parameters were calculated using CMR feature-tracking technology.Patients were followed up by medical records or telephone calls.Composite endpoint event,all-cause death or heart failure hospitalization during follow-up were recorded.Patients were divided into event group and event-free group.Univariable and multivariable Cox proportional hazard regression analyses were performed to determine the risk factors for the outcomes in diabetic HFpEF.The effects of hypertension and obesity on the prognosis of diabetic HFpEF patients and whether they affect the prognostic value of CMR feature-tracking strain analysis were also analyzed.Results:During a follow-up of(7.1±1.8)years,93(43.3%)patients had endpoint events(event group),including 28 all-cause deaths and 65 heart failure hospitalization.Compared with the event-free group(n=122),patients in the event group had significantly lower left ventricular ejection fraction,higher prevalence and extent of late gadolinium enhancement,and significantly reduced global longitudinal strain(GLS),global circumferential strain,global radial strain,and global systolic longitudinal strain rate(all P<0.05).The absolute GLS value was significantly lower in event group than in event-free group,regardless of the presence of hypertension and obesity.Multivariate Cox regression analysis showed that estimated glomerular filtration rate(HR=0.983,95%CI:0.972-0.993,P=0.001),left atrial volume index(HR=1.015,95%CI:1.005-1.026,P=0.004),and GLS(HR=1.142,95%CI:1.060-1.231,P<0.001)were independent risk factors for adverse cardiovascular events in diabetic HFpEF patients.However,adjusted N-terminal pro-brain natriuretic peptide was not an independent prognostic factor.The cut-offvalue of GLS to predict outcome was-14.09%from ROC curve analysis.The Kaplan-Meier curve showed that in patients with and without hypertension and obesity,patients with the GLS>-14.09%had lower event-free survival compared to patients with GLS≤-14.09%(all P<0.05),and the ability of GLS to predict adverse outcomes was not affected by hypertension and obesity.Conclusions:GLS obtained by CMR feature-tracking strain analysis is an independent predictor of adverse outcomes in diabetic HFpEF,and its ability to predict adverse outcomes is independent of hypertension and obesity.

AIM:To investigate the effect of silent information regulator 1(SIRT1)on the degree of aging and apoptosis in a mouse cardiomyocyte aging model through the regulation of Wnt/β-catenin pathway.METHODS:An in vi-tro aging model was established by inducing HL-1 cells with 40 μmol/L D-galactose(D-Gal).The HL-1 cells were trans-fected with a lentivirus overexpressing SIRT1,and the transfection efficiency was verified by Western blot.Western blot was used to detect the protein expression levels of SIRT1,P53,P21,cleaved caspase-3,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),β-catenin,Wnt3a and c-Myc.Senescence-associated β-galactosidase(SA-β-Gal)staining was used to detect cellular senescence level.MTT colorimetric assay was used to detect the cell viability,and flow cytometry was used to detect the apoptosis.RESULTS:Treatment of HL-1 mouse cardiomyocytes with D-Gal led to in-creases in the expression levels of aging-related proteins P53 and P21,as well as an increase in SIRT1 protein level.Addi-tionally,the SA-β-Gal staining showed a significant increase in the positive area(P＜0.05).The expression levels of apop-tosis-related proteins cleaved caspase-3 and Bax were elevated,while the level of the anti-apoptotic protein Bcl-2 was re-duced(P＜0.05).There was a marked decrease in cell viability(P＜0.05),and flow cytometry analysis demonstrated a significant increase in cell apoptosis rate(P＜0.05),which was positively correlated with the duration of D-Gal treatment.Overexpression of SIRT1 notably reduced both aging and apoptosis levels after 48 h of D-Gal treatment(P＜0.05).After D-Gal treatment,the expression levels of β-catenin,c-Myc and Wnt3a proteins were up-regulated.However,these levels were reduced when SIRT1 was overexpressed.Moreover,the addition of LiCl,a Wnt/β-catenin pathway agonist,resulted in increased expression levels of β-catenin,c-Myc and Wnt3a proteins compared with the group with SIRT1 overexpres-sion and D-Gal treatment(P＜0.05).CONCLUSION:SIRT1 inhibits cardiomyocyte apoptosis and alleviates cardiomyo-cyte aging through the Wnt/β-catenin pathway.

Abstract To explore the influence of the occurrence and development of bystander behavior in cyberbullying among adolescents, the paper reviews the factors influencing bystander behavior from the perspective of social ecosystem theory at the individual level, microsystem (family and school factors), peripheral system (contextual factors), macrosystem (cultural factors) and digital environment (media factors). It is pointed out that the future research needs to further explore the internal interaction of micro system, the influence of time system and technological development on bystanders, and the complex interaction between social ecosystems, and design feasible intervention strategies to transform passive bystanders into active interveners.

Objective To prepare glucose transporter 1(Glut1)-targeted doxorubicin(DOX)-loaded liposomes(doxorubicin/polyphyllin H-liposomes,DOX/ppH-LPs)using polyphyllin H(ppH)instead of cholesterol as the liposomal membrane material,and to investigate their in vitro synergistic anti-tumor activity against non-small cell lung cancer(NSCLC).Methods DOX/ppH-LPs were prepared using thin-film hydration,and the formulation was optimized by single-factor investigation.The optimized DOX/ppH-LPs were characterized for morphology,particle size,polydispersity index(PDI),and zeta potential with transmission electron microscopy(TEM)and dynamic light scattering(DLS).Drug loading DL%was determined by high-performance liquid chromatography(HPLC).The storage stability was evaluated by observing in PBS at 4℃for 7 d,and the serum stability was observed in DMEM containing 10%fetal bovine serum(FBS)at 37℃for 48 h.In vitro drug release was studied in PBS at pH 7.4 and pH 5.0 values,respectively.Human NSCLC A549 cells were subjected as the model,MTT assay was performed to detect the proliferation inhibition by DOX/ppH-LPs at different concentrations(0.5,5.0,15.0 μg/mL)and the control group(ppH+DOX/LPs,a physical mixture of free ppH and DOX-loaded liposomes).Fluorescence microscopy was used to observe cellular uptake of DOX/ppH-LPs and DOX/LPs(containing 5 μg/mL DOX)at 15 min and 2 h.Live/dead cell staining was applied to assess apoptosis/necrosis induced by formulations(15 μg/mL DOX)after 48 h incubation.Transwell assay was conducted to evaluate inhibitory effect on cell migration and invasion,and the targeting property and in vitro synergistic anti-NSCLC activity of DOX/ppH-LPs were then comprehensively evaluated.Results The optimal formulation of DOX/ppH-LPs was determined as hydration temperature at 50℃,6 mg DOX,2 mg ppH,and 24 mg lecithin.The prepared DOX/ppH-LPs were in spherical shape,uniform distribution,and at an average particle size of 145.13±22.14 nm,a PDI of 0.15±0.05,a zeta potential of-23.92±1.73 mV,and a DL of 10.13±0.71%for DOX and(1.22±0.21)%for ppH.DOX/ppH-LPs maintained stable particle size,PDI,and exhibited significantly unchanged zeta potential after storage in PBS at 4℃for 7 d or incubation in DMEM containing 10%FBS at 37℃for 48 h,demonstrating excellent physical and serum stability.Both liposomes showed slow release at pH 7.4 value,while drug release was significantly accelerated at pH 5.0 value(P<0.05),indicating pH-sensitive release characteristics.MTT assay revealed that DOX/ppH-LPs exerted significantly stronger cytotoxicity against A549 cells than the ppH+DOX/LPs control group(P<0.05).Compared with ppH+DOX/LPs,DOX/ppH-LPs showed remarkably enhanced cellular uptake in A549 cells(P<0.05),with more DOX localized in the nucleus.Live/dead cell staining showed that at the same DOX concentration(15 μg/mL),the proportion of apoptotic/necrotic cells induced by DOX/ppH-LPs was significantly higher than that of the DOX/LPs control group.Transwell assay demonstrated that there were significantly less cells migrating and invading through the membrane in the DOX/ppH-LPs group than the ppH+DOX/LPs group.Conclusion Glut1-targeted doxorubicin-loaded liposomes(DOX/ppH-LPs)constructed by substituting cholesterol with ppH can target NSCLC cells,significantly enhance the in vitro synergistic anti-NSCLC activity of DOX and ppH.

Objective:To investigate the protective effects of p53/glucose transporter 4 (GLUT4) regulation on cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.Methods:Human myocardial AC16 cells were treated with 33 mmol/L glucose and a hypoxic chamber to establish an in vitro model of high glucose combined with hypoxia/reoxygenation. Based on the glucose concentration in the medium and hypoxia/reoxygenation conditions, AC16 cells were divided into control group, high glucose group, hypoxia/reoxygenation group and high glucose combined with hypoxia/reoxygenation group. On the basis of high glucose combined with hypoxia/reoxygenation group, cells were transfected with empty vector, p53 small interfering RNA (siRNA), and co-transfected with p53 and GLUT4 siRNA to establish negative control group, sip53 transfection group, and sip53+siGLUT4 transfection group, respectively. Western blotting was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), p53, GLUT4, dynamin-related protein 1 (Drp1), mitofusin 2 (Mfn2), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartic acid specific protease-3 (Caspase-3). The levels of reactive oxygen species were detected using the 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mitochondria were labeled with the Mito-Tracker Deep Red FM fluorescent probe to assess mitochondrial morphology and their related parameters. Mitochondrial membrance potential was meausred using the JC-1 detection kit. Adenosine triphosphate (ATP) content was determined using an ATP assay kit. Glucose uptake ability was evaluated by measuring the fluorescence intensity of 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy- D-glucose (2-NBDG) using a multifunctional microplate reader. Apoptosis was assessed by TUNEL assay. Results:The relative expression of HIF-1α protein in the high glucose combined with hypoxia/reoxygenation group was 1.189±0.185, higher than that in the control group (0.086±0.071) ( P<0.05). The relative expression of p53 protein in the high glucose combined with hypoxia/reoxygenation group was 1.248±0.194, higher than those in the control group (0.730±0.184), high glucose group (0.932±0.161) and hypoxia/reoxygenation group (1.109±0.151) (all P<0.05). The relative expression of GLUT4 protein in the high glucose combined with hypoxia/reoxygenation group was 0.407±0.140, lower than those in the control group (1.061±0.060) and hypoxia/reoxygenation group (0.781±0.092) (both P<0.05). The fluorescence intensity of reactive oxygen species in the high glucose combined with hypoxia/reoxygenation group was 38.31±1.66, higher than that in the control group (11.59±1.02) ( P<0.05). The number of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (62.00±15.26), lower than those in the control group (136.20±23.55) and high glucose group (96.55±13.72) (both P<0.05). The average mitochondrial area in the high glucose combined with hypoxia/reoxygenation group was (7.02±1.38) μm 2, lower than those in the control group [(13.74±0.67) μm 2], high glucose group [(9.27±1.99) μm 2] and hypoxia/reoxygenation group [(9.64±2.36) μm 2] (all P<0.05). The average perimeter of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (9.10±1.14) μm, lower than those in the control group [(13.35±0.69) μm] and the hypoxia/reoxygenation group [(10.83±1.58) μm] (all P<0.05). The number of mitochondrial branches was 53.73±9.49, lower than those in the control group (147.10±25.99), high glucose group (97.08±13.65) and hypoxia/reoxygenation group (104.80±24.92) (all P<0.05). The average branch length of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (1.45±0.26) μm, lower than that in the control group [(2.29±0.52) μm] ( P<0.05). The red-green fluorescence intensity ratio in the high glucose combined with hypoxia/reoxygenation group was 0.580±0.133, lower than those in the control group (2.379±0.242), high glucose group (1.200±0.112) and hypoxia/reoxygenation group (0.883±0.076) (all P<0.05). The ATP content of the high glucose combined with hypoxia/ reoxygenation group was (0.025±0.003) μmol/10 5 cells, lower than those of the control group [(0.137±0.012) μmol/10 5 cells], high glucose group [(0.078±0.003) μmol/10 5 cells] and hypoxia/reoxygenation group [(0.073±0.010) μmol/10 5 cells] (all P<0.05). The fluorescence intensity of 2-NBDG in the high glucose combined with hypoxia/reoxygenation group was 257 315±7 951, lower than those in the control group (339 597±10 165), high glucose group (317 293±8 876) and hypoxia/reoxygenation group (314 611±12 228) (all P<0.05). The relative expression of Drp1 protein in high glucose combined with hypoxia/reoxygenation group was 1.203±0.090, higher than those in the control group (0.705±0.170), high glucose group (0.910±0.106) and hypoxia/reoxygenation group (1.002±0.112) (all P<0.05). The relative expression of Mfn2 protein in the high glucose combined with hypoxia/reoxygenation group was 0.706±0.285, lower than those in the control group (1.988±0.139), high glucose group (1.305±0.076) and hypoxia/reoxygenation group (1.131±0.236) (all P<0.05). The relative expression levels of Bax/Bcl-2 and Caspase-3 proteins in the high glucose combined with hypoxia/reoxygenation group were 2.318±0.216 and 1.076±0.076, respectively, higher than those in the control group (0.281±0.046 and 0.442±0.084), high glucose group (0.673±0.043 and 0.662±0.159) and hypoxia/reoxygenation group (0.807±0.293 and 0.835±0.058), respectively (all P<0.05). The TUNEL fluorescence intensity of the high glucose combined with hypoxia/reoxygenation group was 70.55±7.22, higher than those of the control group (14.10±5.93), high glucose group (36.59±2.56) and hypoxia/reoxygenation group (39.04±6.016) (all P<0.05). The relative expression levels of p53 protein in the sip53 transfection group and sip53+siGLUT4 transfection group were 0.322±0.147 and 0.391±0.149, respectively, lower than that in the high glucose combined with negative control group (1.002±0.035) (both P<0.05). The relative expression of GLUT4 protein in the sip53 transfection group was 1.871±0.123, higher than that in the negative control group (1.281±0.232) ( P<0.05). The relative expression of GLUT4 protein in the sip53+siGLUT4 transfection group (0.951±0.193) was lower than that in the sip53 transfection group ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53 transfection group (27.73±0.74) was lower than that in the negative control group (38.83±0.83) ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53+siGLUT4 transfection group (43.12±5.08) was higher than that in the sip53 transfection group ( P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53 transfection group were (92.27±10.10), (9.25±0.42) μm 2, (10.86±0.58) μm, (83.27±13.57), and (1.81±0.21) μm, respectively. They were higher than (52.36±16.87), (7.44±1.49) μm 2, (9.22±1.11) μm, (52.36±16.87), and (1.22±0.26) μm in the negative control group (all P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53+siGLUT4 transfection group were (53.73±9.49), (6.89±0.61) μm 2, (8.88±0.47) μm, (53.73±9.49), and (1.22±0.17) μm, respectively, lower than those in the sip53 transfection group (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53 transfection group were 1.27±0.23, (0.048±0.021) μmol/10 5 cells, 275 923±10 447 and 2.608±0.581, respectively, higher than those in the negative control group [0.53±0.21, (0.020±0.007) μmol/10 5 cells, 254 875±8 078, and 0.687±0.146, respectively] (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53+siGLUT4 transfection group were 0.40±0.08, (0.011±0.012) μmol/10 5 cells, 199 511±6 855, and 0.649±0.070, respectively, lower than those in the sip53 transfection group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53 transfection group were 0.759±0.063, 0.446±0.161, 1.048±0.300, and 48.93±1.48 respectively, lower than those (1.065±0.149, 1.197±0.133, 1.847±0.201, and 67.61±9.99) in the negative control group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53+siGLUT4 transfection group were 0.958±0.166, 2.660±0.135, 1.587±0.220, and 63.39±12.84, respectively, higher than those in the sip53 transfection group (all P<0.05). Conclusions:Under the condition of high glucose combined with hypoxia/reoxygenation, p53 induces cardiomyocyte injury by down-regulating GLUT4. Inhibition of p53 can increase the expression of GLUT4, thereby reducing cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.

Objective:To analyze the effects of the disease and injury spectrum on health-adjusted life expectancy (HALE) among permanent residents aged 55 and above in Shenzhen from 2016 to 2030.Methods:Based on the mortality surveillance data and the permanent resident population data in Shenzhen from 2016 to 2022, the Sullivan method was used to calculate the HALE during 2016—2022. The Bayesian age-period-cohort model and the grey system model were used to predict the HALE during 2023—2030. The HALE changes in the two periods were decomposed into the contributions of 20 categories of diseases and injuries, respectively.Results:From 2016 to 2022, the HALE increased from 31.41 years (95% CI: 30.50-32.32) to 33.57 years (95% CI: 32.47-34.67). During this period, the mortality effect of neurological disorders slowed the increase of HALE, with a reduction of 0.27 years. By 2030, it is anticipated that the HALE will reach 36.40 years (95% CI: 34.78-38.01). This is expected to be influenced by the mortality effects of nutritional deficiencies (-0.40 years) and mental disorders (-0.29 years), as well as the disability effects of musculoskeletal disorders (-0.66 years), skin and subcutaneous diseases (-0.21 years) and nutritional deficiencies (-0.13 years). Conclusion:The HALE of permanent residents aged 55 years and above in Shenzhen demonstrated an increasing trend over time. Greater attention should be paid to the adverse effects of neurological disorders, nutritional deficiencies, mental disorders, musculoskeletal disorders, and skin and subcutaneous diseases on the continuous increase of HALE in this population.