BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective : To explore the role of semaphoring 6d(SEMA6D) in the malignant progression of triple-negative breast cancer(TNBC). Methods : Bioinformatics and Immunohistochemistry(IHC) were used to analyze the expression level of SEMA6D in TNBC and paracancer non-tumor tissues and its relationship with patients′ clinicopathological features. MDA-MB-231 cell line stably knocking down the expression of SEMA6D was constructed, and the effects of SEMA6D on migration and invasion of TNBC cells were investigated by Wound-healing assays and Transwell assays. cBioPortal and GEPIA2 databases were used to screen out the gene negatively associated with it, namely aurora kinase A(AURKA). Bioinformatics and IHC were used to analyze the expression level of AURKA in TNBC and paracancer non-tumor tissues and its relationship with patients' clinicopathological features. Western blot assay was used to analyze the expression of AURKA and the effect of epithelial-mesenchymal transition(EMT) makers Claudin-1, N-cadherin and Vimentin after knocking downSEMA6D. Results: Bioinformatics analysis and IHC results showed that the expression of SEMA6D in TNBC tissues was significantly lower than that in paracancer non-tumor tissues(bothP<0.05). The expression of AURKA in TNBC tissues was significantly higher than that in paracancer non-tumor tissues(bothP<0.05), SEMA6D and AURKA were significantly negatively correlated in TNBC(P<0.01). Both low expression of SEMA6D and high expression of AURKA were positively correlated with tumor size, tumor histological grade, clinical stage and lymph node metastasis in TNBC patients(allP<0.05). The knockdown ofSEMA6Dsignificantly promoted the migration and invasion ability of TNBC cells(bothP<0.01). Western blot results showed that the knockdown ofSEMA6Dupregulated AURKA expression, promoted the expression of N-cadherin and Vimentin, and inhibited the expression of Claudin-1 in tumor cells. Conclusion Down-regulation of SEMA6D expression in TNBC may be involved in the malignant progression of TNBC through up-regulation of AURKA expression and promotion of EMT.

Objective : To explore the expression of prohibitin2(PHB2) in breast cancer and its effect on the biological behaviors of tumor cells. Methods : Immunohistochemistry was used to detect the expression of PHB2 protein in breast cancer tissues and its relationship with clinicopathologic features. Breast cancer stable transient cell lines were constructed with knockdown and overexpression ofPHB2, respectively. The effects of PHB2 on cell proliferation, migration and invasion ability were detected by clone formation assay, scratch assay and Transwell assay. Western blot(WB) was used to detect the effects of PHB2 on the expression of epithelial-mesenchymal transition(EMT)-related markers, including E-cadherin, N-cadherin, Snail family transcriptional repressor 1(Snail) protein, Vimentin, and Claudin-1. The effect of PHB2 on tumorigenicityin vivowas detected by subcutaneous tumor formation assay in nude mice. Results: The result of immunohistochemical showed that PHB2 was highly expressed in breast cancer and the expression of PHB2 was significantly positive correlated with tumor size, human epidermal growth factor receptor-2(HER-2) status and proliferation index Ki-67 levels(P<0.05). Clone formation assay, scratch assay and Transwell assay revealed that knockdown ofPBH2significantly inhibited the proliferation, migration and invasion ability of breast cancer cells(P<0.01), while the overexpression ofPHB2significantly promoted cell proliferation, migration and invasion(P<0.01). The result of subcutaneous tumor formation experiment in nude mice revealed a significant decrease in tumor volume and weight in knockdownPHB2mice(P<0.000 1), whilePHB2overexpression tumors significantly increased in volume and weight(P<0.001).WB assay showed that the protein expression of epithelial marker E-cadherin increased, while the expressions of mesenchymal markers N-cadherin, Snail and Vimentin decreased significantly afterPHB2knockdown with them in control cells(P<0.01). The expression of Claudin-1 decreased, while the expressions of N-cadherin, Snail and Vimentin increased significantly inPHB2overexpression cells(P<0.05). Conclusion PHB2 is highly expressed in breast cancer and promotes multiple malignant biological behaviors in tumor cells, suggesting PHB2 may be a potential target for breast cancer diagnosis and treatment.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective:To analyze the anatomical characteristics and surgical management measures of acute Stanford type A aortic dissection (AAD) involving coronary arteries, and to preliminarily explore the clinical efficacy of different coronary artery treatment techniques.Methods:A retrospective analysis was conducted on the clinical data of 42 patients who underwent surgery for AAD involving coronary arteries in Hunan Provincial People′s Hospital from January 2022 to May 2025. They were divided into the MI group (14 cases) and the nMI group (28 cases) according to whether they had acute myocardial infarction before surgery. The clinical data such as the actual surgical methods and mortality in the two groups were summarized.Results:Among 294 surgeries, 42 cases (14.3%) had definite coronary artery involvement, including 14 cases in the MI group and 28 cases in the nMI group; 1 case had bilateral coronary artery involvement and 41 cases had right coronary artery involvement. Regarding injury types: 16 cases were of the coronary trunk compression type, 12 cases were of the sinus intimal tear neal to ostium type, and 14 cases were of the coronary trunk intimal type. There was no statistically significant difference in the types of coronary artery involvement between the two groups ( P>0.05). There were 18 cases of Sun′s procedure with preserved aortic sinus and aortic valve, 7 cases of Bentall procedure without bypass, and 17 cases of Bentall procedure plus bypass. There was no statistically significant difference in the surgical plans between the two groups ( P>0.05). There were 4 deaths within 30 days (2 cases in each group). Conclusions:AAD involving coronary arteries is a critical condition, and accurate diagnosis is somewhat difficult. Myocardial ischemia is not significantly associated with the type of coronary artery involvement. The surgical plan depends on the type of coronary artery involvement. The classification method in this study is conducive to selecting appropriate surgical methods and improving surgical prognosis.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective:To analyze the anatomical characteristics and surgical management measures of acute Stanford type A aortic dissection (AAD) involving coronary arteries, and to preliminarily explore the clinical efficacy of different coronary artery treatment techniques.Methods:A retrospective analysis was conducted on the clinical data of 42 patients who underwent surgery for AAD involving coronary arteries in Hunan Provincial People′s Hospital from January 2022 to May 2025. They were divided into the MI group (14 cases) and the nMI group (28 cases) according to whether they had acute myocardial infarction before surgery. The clinical data such as the actual surgical methods and mortality in the two groups were summarized.Results:Among 294 surgeries, 42 cases (14.3%) had definite coronary artery involvement, including 14 cases in the MI group and 28 cases in the nMI group; 1 case had bilateral coronary artery involvement and 41 cases had right coronary artery involvement. Regarding injury types: 16 cases were of the coronary trunk compression type, 12 cases were of the sinus intimal tear neal to ostium type, and 14 cases were of the coronary trunk intimal type. There was no statistically significant difference in the types of coronary artery involvement between the two groups ( P>0.05). There were 18 cases of Sun′s procedure with preserved aortic sinus and aortic valve, 7 cases of Bentall procedure without bypass, and 17 cases of Bentall procedure plus bypass. There was no statistically significant difference in the surgical plans between the two groups ( P>0.05). There were 4 deaths within 30 days (2 cases in each group). Conclusions:AAD involving coronary arteries is a critical condition, and accurate diagnosis is somewhat difficult. Myocardial ischemia is not significantly associated with the type of coronary artery involvement. The surgical plan depends on the type of coronary artery involvement. The classification method in this study is conducive to selecting appropriate surgical methods and improving surgical prognosis.

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.

Purpose To explore the expression of autoph-agy-related 7(ATG7)in breast cancer and its effect on the breast cancer development.Methods Immunohistochemistry(IHC)was used to detect ATG7 protein expression in breast cancer tissues and the relationship between ATG7 and clinico-pathological features was analyzed.ShRNA was used to interfere with the expression of ATG7 in breast cancer cell line MCF-7.Puromycin was used to screen for stably transfected cells and Western blot was used to detect transfection efficiency.The effect of ATG7 knockdown cells on proliferation ability was de-tected by CCK8 and clone formation experiments.The effect of ATG7 knockdown cells on tumorigenicity in vivo was detected by subcutaneous tumor formation experiment in nude mice.Results IHC showed that ATG7 expression in breast cancer tissues was mainly localized in cytoplasm,and its expression was significant-ly correlated with tumor size and Ki67 expression(P＜0.05).ATG7-shRNA significantly interfered with ATG7 expression in breast cancer cells MCF-7.CCK8 and clone formation experi-ments showed that ATG7 knockdown promoted the cell prolifera-tion compared with the control group.The experiment of subcu-taneous tumor formation in nude mice showed that the tumor for-mation ability of mice was significantly increased after ATG7 knockdown compared with the control group.Conclusion ATG7 may inhibit the proliferation capacity of breast cancer and could be a potential target for breast cancer therapy.

Objective To investigate the clinical characteristics of Charcot-Marie-Tooth disease(CMT),and conduct genetic analysis.Methods The clinical data of 2 families were retrospectively analyzed.Results The proband of family 1 had atrophy of bilateral thigh and calf muscles,serum creatine kinase(CK)was 292 U/L,and EMG examination showed peripheral nerve damage of upper and lower limbs(mainly axonal).Genetic testing revealed that the proband carried a heterozygous mutation of NEFH:NM＿02107:c.3057dupG:p.K1020Efs*43.According to American College of Medical Genetics and Genomics(ACMG),the variant of NEFH gene was interpreted as likely pathogenic(PS3＿moderate+PM2+PM4+PP1).The proband of family 2 had scoliosis,calf muscle atrophy,flat foot,blood creatine kinase 80 U/L,and EMG examination showed peripheral nerve damage in the upper and lower limbs(mainly axonal).Genetic testing revealed that the proband carried a heterozygous mutation of the MFN2:NM＿014874:c.746C＞G:p.S249C.This mutation had not been reported and included in the relevant literature,and was likely to be pathogenic according to the ACMG regulation rating(Likely Pathogenic:PM1+PM2+PM5+PP3).Conclusions The clinical manifestations of the two families are muscle weakness with muscle atrophy,normal or mild elevation of creatine kinase,disappearance of tendon reflex,arched foot,and electromyography indicating neurogenic damage.Gene testing reveals that the probands carried heterozygous mutations in the NEFH and MFN2 genes,respectively.