Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.

To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

Gastric variceal rupture and bleeding and hepatic encephalopathy are common and life-threatening complications in decompensated cirrhosis. As a minimally invasive interventional technique， balloon-occluded retrograde transvenous obliteration （BRTO） has made significant progress in the clinical management of gastric varices and hepatic encephalopathy in recent years. This article systematically reviews the technical principles， indications （e.g.， isolated gastric varices and refractory hepatic encephalopathy）， clinical efficacy （an acute hemostasis rate of 85% — 95%， a 1-year rebleeding rate of <15%， and an improvement rate of 60% — 80% for hepatic encephalopathy）， and safety （including complications such as renal impairment and elevated portal vein pressure） of BRTO. Meanwhile， this article discusses the advantages and disadvantages of BRTO and conventional treatment modalities （e.g.， transjugular intrahepatic portosystemic shunt and endoscopic treatment） and reviews the latest technological improvements in recent years， such as coil-assisted retrograde transvenous obliteration and plug-assisted retrograde transvenous obliteration. Future research should focus on the precision of patient selection （e.g.， stratification based on hemodynamic parameters）， the optimization of embolic materials （e.g.， application of new biodegradable embolic agents）， and the development of individualized treatment regimens， so as to improve efficacy and reduce the risk of complications.

ObjectiveTo perform metabolic associated fatty liver disease （MAFLD） screening among individuals attending community health institutions， to identify the patients at a low， moderate or high risk of advanced liver fibrosis based on fibrosis-4 index （FIB-4） and liver stiffness measurement （LSM） measured by liver transient elastography， and to implement stratified management. MethodsA cross-sectional study was conducted among 630 individuals attending Beijing Baizhifang Community Health Service Center from January to July 2024， and they were divided into MAFLD group and non-MAFLD group. According to body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<23 kg/m²） and non-lean MAFLD group （BMI≥23 kg/m²）. The above groups were compared in terms of demographic features， laboratory markers， hepatic steatosis， and LSM. Fibrosis risk stratification was performed for MAFLD patients based on FIB-4 and LSM， and a closed-loop management system involving referral to tertiary hospitals and follow-up at community health institutions was implemented. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThere were 445 individuals （70.6%） in the MAFLD group and 185 individuals （29.4%） in the non-MAFLD group. Compared with the non-MAFLD group， the MAFLD group had a significantly lower proportion of male individuals （χ²=4.299， P<0.05）， a significant reduction in the level of high-density lipoprotein cholesterol （Z=3.484， P<0.05）， and significant increases in body weight （Z=-7.366， P<0.05）， BMI （Z=-9.740， P<0.05）， waist circumference （Z=-6.397， P<0.05）， hip circumference （Z=-6.935， P<0.05）， alanine aminotransferase （ALT） （Z=-2.765， P<0.05）， fasting blood glucose （Z=-3.646， P<0.05）， triglyceride （TG） （Z=-6.569， P<0.05）， total cholesterol （Z=-2.033， P<0.05）， low-density lipoprotein cholesterol （Z=-2.935， P<0.05）， controlled attenuation parameter （CAP） （Z=-19.784， P<0.05）， and LSM （Z=-5.703， P<0.05）. Within the MAFLD group， there were 124 individuals （27.9%） in the lean MAFLD group and 321 individuals （72.1%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly lower body weight （Z=-12.414， P<0.05）， BMI （Z=-16.363， P<0.05）， waist circumference （Z=-7.733， P<0.05）， hip circumference （Z=-8.595， P<0.05）， ALT （Z=-2.835， P<0.05）， aspartate aminotransferase （Z=-1.972， P<0.05）， TG （Z=-2.407， P<0.05）， CAP （Z=-4.429， P<0.05）， degree of steatosis （χ²=16.588， P<0.05）， and LSM （Z=-3.908， P<0.05）. Based on the results of FIB-4 and LSM， 76 patients at a moderate or high risk of liver fibrosis should be referred to a higher-level hospital for further management. ConclusionThe detection rate of MAFLD reaches 70.6% among the individuals attending community health institutions， among whom 76 （17.1%） should be referred to a higher-level hospital. Establishing a liver fibrosis risk stratification and management system based on FIB-4 and LSM among MAFLD individuals in communities provides a practical pathway for chronic disease management and referral system construction in community health institutions.

To analyze global trends and research hotspots in exercise intervention for overweight and obesity from 2010 to 2024, to provide novel perspectives for comprehensive management research on overweight and obesity.

Artificial intelligence (AI) has emerged as a transformative force in healthcare, with applications spanning diagnostics to drug development. However, its integration into drug regulation remains nascent, with varying degrees of adoption and implementation across different regulatory bodies worldwide. This review aims to provide a comprehensive overview of the current state of AI in drug regulation, encapsulating AI-related policies, initiatives, and its practical application in regulatory agencies globally. It further discusses the challenges and future prospects of AI in this field. The findings reveal that numerous agencies have launched action plans and initiatives to incorporate AI, aiming to streamline regulatory processes and enhance data-driven regulatory decision-making. Moreover, AI's deployment in safety surveillance, workflow optimization, and regulatory science research is expanding, highlighting its increasing impact on drug regulation. Nonetheless, key challenges persist, such as data quality and reliability, technical limitations, talent shortage and the absence of standards. The review concludes that interdisciplinary collaboration is crucial to harness AI's full potential in drug regulation and overcoming its current limitations. In the future, AI may become a pivotal catalyst in drug regulation, promising a new era of enhanced scrutiny, efficiency, and innovation that will benefit public health on a global scale.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVE To observe the causal association between colorectal cancer and sepsis by means of bidirec-tional two-sample Mendelian randomization(MR).METHODS The Genome Wide Association Study(GWAS)datasets for colorectal cancer and sepsis were retrieved from the GWAS databases between its establishment and Feb.1,2024.MR was carried out for the colorectal cancer and sepsis interacting as exposure and outcome factors.The single nucleotide polymorhpism(SNPs)that were significantly associated with the exposure factors were screened out by setting P as less than 5.0× 10-8,r2 less than 0.001,the genetic distance 10,000 kb.The SNPs that were remarkably associated with the exposure factors were extracted from the GWAS datasets of the outcome variables,the instrumental variable were finally obtained,the inverse variance weighting(IVW)was taken as the main approach for the causal inference.The level pleiotropy was tested by using MR Egger method and MR-PRESSO,the heterogeneity was tested by IVW method and MR-Egger method,the sensitivity was analyzed by leave-one-out method,and the robustness of the result was tested.RESULTS A total of 30 SNPs were screed out by setting the colorectal cancer as exposure factor and the sepsis as outcome variable(F＞10);there was causal as-sociation between the colorectal cancer and the sepsis(OR=28.955,95％CI:1.215 to 690.052,P=0.037).Totally 14 SNPs were screened out by setting the sepsis as exposure factor and the colorectal cancer as treatment variable(F＞10),and there was no causal association between the colorectal cancer and the sepsis(OR=0.999,95％CI:0.997 to 1.002,P=0.674).There was no level pleiotropy in the instrumental variables during the two times of MR analysis;there was no heterogeneity in the instrumental variables,and the result of the MR analysis was robust.CONCLUSION There is causal association between the colorectal cancer and the increases of risk of sepsis.But there is no causal association between the sepsis and the increase of risk of colorectal cancer.

Objective:To explore the effect of prognosis appearance of the combination of microneedle array radiofrequency and CO2 array laser on psychological stress response of patients with facial acne scar.Methods:A total of 100 patients with facial acne scar,who admitted to Chengdu Second People's Hospital from August 2020 to August 2020,were selected,and they were divided into study group and control group,with 50 cases in each group.Study group adopted combined treatment with microneedle array radiofrequency and CO2 array laser,and control group adopted microneedle array radiofrequency to conduct treatment.The curative effect after treatment was compared between two groups.The Vancouver scar scale(VSS)was adopted to score the scar condition of patients,and Hamilton anxiety(HAMA)rating scale,Hamilton depression(HAMD)of rating scale and self-esteem scale(SES)were adopted to evaluate the psychological stress response of patients,and the score of the comprehensive evaluation questionnaire of quality of life(GQOLI-74 score)was adopted to evaluate the difference of quality of life of patients between before and after treatment.Results:After treatment,the overall curative effect of study group was 92.00%,which was better than 72.00%of control group,and the difference was significant(x2=6.775,P<0.05).The VSS scores of study group after received treatment of 2,4 times were significantly lower than those before treatment,and were lower than those of control group,and the differences of those between two groups were significant(t=5.850,9.040,P<0.05),respectively.After treatment,the SES scores of two groups all rose,and the HAMD and HAMA scores of two groups all reduced,and the three scores of study group were all better than those of control group,and the differences of them between two groups were significant(t=3.456,3.909,6.063,P<0.05).Pearson correlation showed that the VSS score was negatively correlated with the SES score(r=-0.249,P<0.05),and was positively correlated with the HAMD score and the HAMA score(r=0.653,0.695,P<0.05),respectively.After treatment,the GQOLI-74 scores of each indicator(material and life,physical function,psychological function,and social function)of two groups rose all,and the GQOLI-74 scores of study group were all better than those of control group,and the differences of them between two groups were significant(t=4.324,7.497,3.870,4.534,P<0.05),respectively.Conclusion:The combination of microneedle array radiofrequency and CO2 array laser has better curative effect in treating facial acne scar,which can effectively promote prognosis appearance,and relieve psychological stress response,and improve the quality of life.

Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.