Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Renal cell carcinoma(RCC)is a malignant tumor that originates from the epithelial cells of the re-nal tubules,comprising 80%to 90%of all malignant renal tumors.With the dual pressures of population growth and ag-ing,both the incidence and mortality rates of RCC are on the rise.PANoptosis is a newly identified form of cell death,con-trolled by the PANoptosome complex,and exhibits characteristics of three programmed cell death pathways,pyroptosis,apoptosis,and necroptosis.Increasing research indicates that the occurrence of PANoptosis is associated with tumor devel-opment,suggesting its potential as a new therapeutic strategy for renal carcinoma.This article reviews the definition of PANoptosis,the structure of the PANoptosome protein complex,and its impact on the PANoptosis process.Additionally,it explores the interactions between PANoptosis,pyroptosis,apoptosis and necroptosis,and their effects on RCC.

Renal cell carcinoma(RCC)is a malignant tumor that originates from the epithelial cells of the re-nal tubules,comprising 80%to 90%of all malignant renal tumors.With the dual pressures of population growth and ag-ing,both the incidence and mortality rates of RCC are on the rise.PANoptosis is a newly identified form of cell death,con-trolled by the PANoptosome complex,and exhibits characteristics of three programmed cell death pathways,pyroptosis,apoptosis,and necroptosis.Increasing research indicates that the occurrence of PANoptosis is associated with tumor devel-opment,suggesting its potential as a new therapeutic strategy for renal carcinoma.This article reviews the definition of PANoptosis,the structure of the PANoptosome protein complex,and its impact on the PANoptosis process.Additionally,it explores the interactions between PANoptosis,pyroptosis,apoptosis and necroptosis,and their effects on RCC.

Objective:To establish the predictive model for major adverse cardiovascular events(MACE) following endovascular repair in elderly patients with abdominal aortic aneurysm(AAA).Methods:The clinical data and postoperative MACE were retrospectively collected from elderly patients with AAA who underwent their first endovascular aneurysm repair(EVAR)in Beijing Hospital and Tibet Autonomous Region People's Hospital between January 2016 and December 2023.Patients were randomly divided into training and validation cohorts at a ratio of 7∶3.Predictive models were using logistic regression, LASSO regression, random forest, linear discriminant analysis, na?ve Bayes, k-nearest neighbor algorithm, support vector machine, decision tree, and AdaBoost.Models were evaluated using receiver operating characteristic(ROC)curves.Results:A total of 171 elderly AAA patients were enrolled, aged 60 to 94 years(mean 73.0 ± 7.5 years), of whom 145 were male.MACE occurred after EVAR in 30 patients(17.5%). LASSO regression identified monocyte count, history of coronary artery disease, the ratio of maximum AAA diameter to body mass index(DBR), neutrophil-lymphocyte count ratio(NLR), and age as significant predictors, yielding an area under the ROC curve(AUC)of 0.816.Logistic regression achieved an AUC of 0.813 in the training cohort and 0.772 in the validation cohort.Among all models, AdaBoost demonstrated the best performance, with an AUC of 0.92 in the validation cohort.Conclusions:Age, monocyte count, DBR, NLR and creatinine could predict the occurrence of MACE after EVAR in AAA patients.The AdaBoost model provides the most accurate prediction of postoperative MACE.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Objective:To establish the predictive model for major adverse cardiovascular events(MACE) following endovascular repair in elderly patients with abdominal aortic aneurysm(AAA).Methods:The clinical data and postoperative MACE were retrospectively collected from elderly patients with AAA who underwent their first endovascular aneurysm repair(EVAR)in Beijing Hospital and Tibet Autonomous Region People's Hospital between January 2016 and December 2023.Patients were randomly divided into training and validation cohorts at a ratio of 7∶3.Predictive models were using logistic regression, LASSO regression, random forest, linear discriminant analysis, na?ve Bayes, k-nearest neighbor algorithm, support vector machine, decision tree, and AdaBoost.Models were evaluated using receiver operating characteristic(ROC)curves.Results:A total of 171 elderly AAA patients were enrolled, aged 60 to 94 years(mean 73.0 ± 7.5 years), of whom 145 were male.MACE occurred after EVAR in 30 patients(17.5%). LASSO regression identified monocyte count, history of coronary artery disease, the ratio of maximum AAA diameter to body mass index(DBR), neutrophil-lymphocyte count ratio(NLR), and age as significant predictors, yielding an area under the ROC curve(AUC)of 0.816.Logistic regression achieved an AUC of 0.813 in the training cohort and 0.772 in the validation cohort.Among all models, AdaBoost demonstrated the best performance, with an AUC of 0.92 in the validation cohort.Conclusions:Age, monocyte count, DBR, NLR and creatinine could predict the occurrence of MACE after EVAR in AAA patients.The AdaBoost model provides the most accurate prediction of postoperative MACE.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.