Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

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To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC cases.Despite advancements in targeted therapies and localized treatments,the 5-year survival rate remains low,indicating limited efficacy of current approaches.The advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has brought new hope for patients with PLC.However,the liver's unique immune microenvironment presents significant challenges to the effectiveness of immunotherapy in HCC.This article reviews recent research developments in liver cancer immunotherapy,focusing on ICIs,combination therapies,emerging treatments,and prospective future directions.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC cases.Despite advancements in targeted therapies and localized treatments,the 5-year survival rate remains low,indicating limited efficacy of current approaches.The advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has brought new hope for patients with PLC.However,the liver's unique immune microenvironment presents significant challenges to the effectiveness of immunotherapy in HCC.This article reviews recent research developments in liver cancer immunotherapy,focusing on ICIs,combination therapies,emerging treatments,and prospective future directions.

AIM: To investigate the alterations in corneal aberration and relative refractive power following the reduction of back optic zone diameters(BOZD)of orthokeratology lenses.METHODS: Myopic children aged 8-12 years, deemed suitable and willing to wear orthokeratology lenses, were randomly allocated to wear lenses with a 6.0 mm BOZD or a 5.0 mm BOZD. Data collection included changes in higher-order aberrations, relative refractive power and the treatment zone diameter of the two groups after wearing lenses for 1 d, 1 wk, 1, and 3 mo. The correlation of increase in corneal higher-order aberrations with refractive power was analyzed.RESULTS: The increases in total higher-order aberrations, spherical aberrations and coma aberrations varied over time following lens wear(all P<0.001), and there were no statistically significant differences in the changes of total higher-order aberrations and coma aberrations between the two groups of patients(all P>0.05). A significant difference was observed in the increment of spherical aberrations in the 5 mm range between the two groups of patients, which varied over time(Ftime=40.179, Ptime<0.001; Fgroup=11.948, Pgroup=0.001; Finteraction=3.262, Pinteraction=0.03). A significant difference was observed in the increment of spherical aberrations in the 4 mm range between the two patient groups(Ftime=34.462, Ptime<0.001; Fgroup=13.094, Pgroup<0.001; Finteraction=1.372, Pinteraction=0.25). There was no statistically significant distinction in relative refractive power between the two groups(Fgroup=0.048, Pgroup=0.83; Finteraction=1.208, Pinteraction=0.31); however, relative refractive power changed over time(Ftime=40.030, Ptime<0.001). The difference in treatment zone diameter between the two groups was statistically significant, with changes over time(Ftime=11.212, Ptime<0.001; Fgroup=74.073, Pgroup<0.001; Finteraction=0.312, Pinteraction=0.82). The total higher-order aberrations, spherical aberrations, and coma aberrations in 4, 5 and 6 mm range showed a positive correlation with relative refractive power values(all P<0.001). Statistically significant difference was observed in the axial length between the two groups after wearing lenses for 3, 6 and 12 mo(Ftime=185.398, Ptime<0.001; Fgroup=5.618, Pgroup=0.02; Finteraction=2.315, Pinteraction=0.11).CONCLUSION: Orthokeratology lenses leaded to elevated higher-order aberrations. Orthokeratology lenses with smaller BOZD produced significantly greater spherical aberrations at 4 and 5 mm range and smaller treatment zone diameters. The corneal total higher-order aberration was positively correlated with relative refractive power. Wearing orthokeratology lenses with a smaller BOZD can cause slower axial growth and better myopia control.

Objective:To explore the correlation between the lesion imaging characteristics and the parent artery plaques detected by high-resolution magnetic resonance imaging (HR-MRI) in patients with recent small subcortical infarction (RSSI) in the lenticulostriate artery territory with mild stenosis of the parent artery.Methods:Consecutive patients with RSSI in the lenticulostriate artery territory admitted to Department of Neurology, the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were prospectively enrolled. Patients with stenosis of <50% in the ipsilateral middle cerebral artery (MCA) who had completed HR-MRI were included. The RSSI lesion characteristics, such as the lowest slice involved (LS), total number of slices involved (TNS) were evaluated based on serialized axial levels of diffusion weighted imaging. HR-MRI was utilized to assess the presence of dorsal superior plaques in the M1 segment of the responsible MCA. Patients were divided into plaque group and non-plaque group based on the presence or absence of plaque. Logistic regression analysis was carried out to identify the lesion characteristics associated with the presence of dorsal superior plaques in the MCA. A receiver operating characteristic (ROC) curve was employed to estimate the predictive efficacy of these parameters for MCA plaques using the area under the curve (AUC) and the optimal cut-off point.Results:A total of 112 patients were incorporated into the final analysis. The age of these patients was (57.08±11.90) years, and 78 patients (69.64%) were male. Plaques were detected on the dorsal superior wall of the MCA in 57 cases (50.89%) as the plaque group, and the other 55 cases (49.11%) were regarded as the non-plaque group. Multivariate Logistic regression revealed that LS was significantly associated with MCA plaques ( OR=0.674, 95% CI 0.485-0.937, P=0.019). The optimal cut-off point (LS≤1) was determined by ROC curve analysis (AUC=0.640, P=0.007). Conclusion:The findings suggest that in RSSI patients with mild stenosis of the parent artery, an LS≤1 is notably associated with the presence of dorsal superior plaques on MCA as detected by HR-MRI.

Objective To analyze the predictive value of apolipoprotein B(apoB)and apoB to apolipoprotein A1(apoA1)ratio(apoB/A1)in acute myocardial infarction(AMI)of phlegm blended with blood stasis syndrome.Methods A total of 200 patients with AMI confirmed by coronary angiography in Foshan Hospital of Traditional Chinese Medicine during the trial period were collected.Data collection covered the basic information of gender,age,medical history of hypertension,coronary heart disease and diabetes mellitus,and smoking history,the information of four diagnostic methods of traditional Chinese medicine(TCM),and relevant indicators of blood lipids,the number of lesioned branches of coronary arteries and the Gensini scores.The predictive value of apoB and apoB/A1 for AMI of phlegm blended with blood stasis syndrome was explored by univariate Logistic regression analysis and multivariate Logistic regression analysis as well as by plotting the Receiver Operating Characteristic(ROC)curves.Results(1)Among the 200 AMI patients,41 cases were differentiated as qi deficiency and blood stasis syndrome,36 cases as qi stagnation and blood stasis syndrome,74 cases as phlegm blended with blood stasis syndrome,and 49 cases as other syndromes(including 16 cases of cold accumulation in heart vessels syndrome,22 cases of qi and yin deficiency syndrome,and 11 cases of healthy-qi deficiency and yang collapse syndrome).(2)The difference of Gensini scores among the patients with various TCM syndrome types were statistically significant(H=43.735,P=0.000<0.001).And the Gensini scores in the patients with syndromes of qi deficiency and blood stasis,qi stagnation and blood stasis,and phlegm blended with blood stasis were relatively high,being 60.0(43.0,87.0),70.0(48.5,84.0)and 65.0(40.0,95.0)points,respectively,which were higher than that of the other TCM syndrome types[44.0(32.0,64.0)points].The pairwise comparison between various TCM syndrome types showed that the differences were statistically significant(P<0.05).However,there was no statistically significant difference in the number of lesioned branches of coronary arteries among the patients with various TCM syndrome types(H=1.180,P=0.758>0.05).(3)The results of correlation analysis showed that the number of lesioned branches of coronary arteries,Gensini score and apoB/A1 were significantly and positively correlated(r=0.140,P=0.049<0.05;r=0.205,P=0.004<0.01).(4)The results of univariate Logistic regression analysis and multivariate Logistic regression analysis showed that apoB and apoB/A1 were the independent risk factors for phlegm blended with blood stasis syndrome(P<0.01).ROC curve analysis showed that apoB/A-1 exerted a high predictive value for AMI of phlegm blended with blood stasis syndrome,with high sensitivity and specificity.Conclusion It is indicated that ApoB/A1 can be used as an objective indicator for predicting AMI of phlegm blended with blood stasis syndrome in clinical practice.

Objective:To evaluate the incidence and frequency of inappropriate shocks caused by defibrillation lead failure in patients with implantable cardioverter-defibrillators (ICD), and to explore methods for reducing the incidence and frequency of such inappropriate shocks.Methods:This was a single-center retrospective study involving patients treated for defibrillation lead failures at Peking University People′s Hospital between March 2015 and May 2024. Patients were divided into an alarm function group and a non-alarm function group based on whether their ICDs were equipped with lead alarm functions. Clinical data, lead data, and the incidence and frequency of inappropriate shocks were collected and compared between the two groups. A multivariate logistic regression model was used to analyze factors influencing the incidence and frequency of inappropriate ICD shocks. Kaplan-Meier survival curves were plotted to compare the trends in the incidence and frequency of inappropriate shocks over time since ICD implantation between the two groups.Results:A total of 59 patients were enrolled, with a age of (56.7±15.2) years, including 42 males (71%). The lifespan of the failed leads in the entire cohort was 64.0 (36.0, 96.0) months. There were 26 patients in the alarm function group and 33 in the non-alarm function group. The most common manifestations of lead failure were oversensing (85%, 50/59) and abnormal pacing impedance (42%, 25/59). A total of 33 patients (56%, 33/59) experienced inappropriate shock therapy, with an average of 27.3 shocks per patient. The frequency of inappropriate ICD shocks in the non-alarm function group was higher than that in the alarm function group (25.0 (10.0, 60.0) times/year vs. 5.0 (2.8, 7.8) times/year, P=0.001). Multivariate logistic regression analysis showed that oversensing ( OR=2.057, 95% CI 1.125-6.763, P=0.019) was an influencing factor for incidence of inappropriate shocks, while the lead alert function ( OR=0.062, 95% CI 0.005-0.719, P=0.001) was a factor influencing the frequency of inappropriate shocks. Kaplan-Meier survival analysis revealed that the incidence and frequency of inappropriate shocks increased with the duration of ICD implantation in both groups, but the differences were not statistically significant (incidence: log-rank P=0.908; frequency: log-rank P=0.767). Conclusion:The lead alert function can reduce the frequency of inappropriate shocks caused by lead failure.