Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Objective To investigate the predictive value of multimodal ultrasound parameters combined with systemic inflammation response index(SIRI)and neutrophil-to-lymphocyte ratio(NLR)for efficacy of neoadjuvant chemotherapy(NAC)in patients with breast cancer(BC).Methods A total of 132 BC patients in the Provincial Hospital Affiliated to Shandong First Medical University from March 2022 to March 2024 were selected as the study subjects,and they were divided into effective group(n=100)and ineffective group(n=32)according to the NAC results.Multimo-dal ultrasound parameters,SIRI,and NLR before NAC treatment were compared between the two groups.Multivariate Logistic regression analysis was used to explore the influencing factors of ineffective NAC in BC patients.Results After NAC treatment,among 132 BC patients,23 cases achieved complete remission,77 cases achieved partial remission,29 cases had stable disease,and 3 cases had disease progression.The elasticity score and resistance index(RI)in the effective group were significantly lower than those in the ineffective group,while the peak intensity(PI),area under the curve(AUC),and peak systolic velocity(PSV)were significantly higher than those in the ineffec-tive group(P＜0.05).The neutrophil count and monocyte count in the ineffective group were sig-nificantly higher than those in the effective group,while the lymphocyte count was significantly lower than that in the effectivegroup(P＜0.05).Before NAC treatment,the SIRI and NLR in the inef-fective group were significantly higher than those in the effective group(P＜0.05).The proportions of patients with non-triple-negative breast cancer and lymph node metastasis in the ineffective group were significantly higher than those in the effective group(P＜0.05).Multivariate Logistic regres-sion analysis showed that high RI,high SIRI,high NLR,high elasticity score,low PSV,low PI,low AUC,non-triple-negative breast cancer,and lymph node metastasis were risk factors for ineffec-tive NAC in BC patients(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the AUC for predicting the efficacy of NAC in BC by the combination of multimodalultra-sound parameters,SIRI,and NLR was 0.929,which was significantly higher than that of the three independent predictors alone(P＜0.05).Conclusion The combination of multimodal ultrasound parameters,SIRI,and NLR has a high predictive value for the efficacy of NAC in BC and may serve as effective predictors for the efficacy of NAC.

Objective:To evaluate the clinical efficacy of a novel surgical approach of debridement, antibiotics, and implant retention (DAIR) with flap transfer, for treating chronic implant infections in bone tumor patients.Methods:A retrospective review was conducted on nine consecutive patients [6 males, 3 females; median age 35(27, 51) years, range 9-71] who underwent a modified procedure of DAIR plus flap transfer between November 2022 and January 2024. The cohort included six cases of chronic periprosthetic joint infection and three cases of chronic plate and screw infection. Tumor diagnoses included seven primary malignant tumors (osteosarcoma=5, undifferentiated pleomorphic sarcoma of bone=1, synovial sarcoma=1) and two bone metastasis of renal cell carcinoma. The procedure involved wide, radical debridement, meticulous removal of biofilm from implants and surrounding soft tissue, followed by the transfer of a well vascularized musculocutaneous flap to fully envelope the contaminated interface. Pre-operative clinicopathological data, surgical details, postoperative complications and infection recurrence were analyzed.Results:The median interval between initial implantation and debridement was 10.0(3.3, 14.8) months. Median follow-up after debridement was 15.9(15.4, 18.2) months. All nine surgeries were completed as planned: six musculocutaneous flaps, two fasciocutaneous flaps and one muscle-only flap. Implants were preserved in six patients; two required subsequent removal for recurrent infection, and one patient later underwent amputation for tumor recurrence. Infection-free implant survival at 3, 6 and 12 months was 88.9%, 87.5% and 87.5%, respectively. Major complications included one donor-site hematoma, one donor-site sensory deficit and one wound healing delay. All the complications were well management. Both reinfections occurred in proximal tibial prostheses, likely due to limited flap coverage options and local anatomical constraints.Conclusion:Although reinfections happened in two cases DAIR with flap transfer provides promising short-term infection control in patients with chronic implant-associated infections following bone tumor surgery.

To address the limitations of the existing automatic electrocardiogram(ECG)diagnosis models in learning long-term dependencies,an automatic 12-lead long-term ECG signal diagnosis model which combines bidirectional selective state space model(bidirectional mamba,BiMamba)with residual multi-scale receptive field block(RMSF)is proposed:(1)designing a multi-scale receptive field module with residual connections to realize more extensive feature extraction and fusion;(2)introducing BiMamba block to enhance the model's temporal modeling capability by employing both forward and backward temporal processing;(3)using the classifier to process features from BiMamba for accomplishing multi-label ECG classification.Five major diagnostic categories from the PTB-XL dataset are extracted and subjected to 5-fold cross-validation experiments.The experimental results from the comparative study show that BiMamba-RMSF achieves an average accuracy of 89.42%,an average AUC of 0.9356,and an average F1 score of 72.85%,outperforming the other 4 automatic ECG diagnosis models.Additionally,ablation study further validates the effectiveness of BiMamba block.It is demonstrated that the proposed model has a high precision in the multi-label classification for 12-lead long-term ECG signals.

Objective:To evaluate the clinical efficacy of a novel surgical approach of debridement, antibiotics, and implant retention (DAIR) with flap transfer, for treating chronic implant infections in bone tumor patients.Methods:A retrospective review was conducted on nine consecutive patients [6 males, 3 females; median age 35(27, 51) years, range 9-71] who underwent a modified procedure of DAIR plus flap transfer between November 2022 and January 2024. The cohort included six cases of chronic periprosthetic joint infection and three cases of chronic plate and screw infection. Tumor diagnoses included seven primary malignant tumors (osteosarcoma=5, undifferentiated pleomorphic sarcoma of bone=1, synovial sarcoma=1) and two bone metastasis of renal cell carcinoma. The procedure involved wide, radical debridement, meticulous removal of biofilm from implants and surrounding soft tissue, followed by the transfer of a well vascularized musculocutaneous flap to fully envelope the contaminated interface. Pre-operative clinicopathological data, surgical details, postoperative complications and infection recurrence were analyzed.Results:The median interval between initial implantation and debridement was 10.0(3.3, 14.8) months. Median follow-up after debridement was 15.9(15.4, 18.2) months. All nine surgeries were completed as planned: six musculocutaneous flaps, two fasciocutaneous flaps and one muscle-only flap. Implants were preserved in six patients; two required subsequent removal for recurrent infection, and one patient later underwent amputation for tumor recurrence. Infection-free implant survival at 3, 6 and 12 months was 88.9%, 87.5% and 87.5%, respectively. Major complications included one donor-site hematoma, one donor-site sensory deficit and one wound healing delay. All the complications were well management. Both reinfections occurred in proximal tibial prostheses, likely due to limited flap coverage options and local anatomical constraints.Conclusion:Although reinfections happened in two cases DAIR with flap transfer provides promising short-term infection control in patients with chronic implant-associated infections following bone tumor surgery.

To address the limitations of the existing automatic electrocardiogram(ECG)diagnosis models in learning long-term dependencies,an automatic 12-lead long-term ECG signal diagnosis model which combines bidirectional selective state space model(bidirectional mamba,BiMamba)with residual multi-scale receptive field block(RMSF)is proposed:(1)designing a multi-scale receptive field module with residual connections to realize more extensive feature extraction and fusion;(2)introducing BiMamba block to enhance the model's temporal modeling capability by employing both forward and backward temporal processing;(3)using the classifier to process features from BiMamba for accomplishing multi-label ECG classification.Five major diagnostic categories from the PTB-XL dataset are extracted and subjected to 5-fold cross-validation experiments.The experimental results from the comparative study show that BiMamba-RMSF achieves an average accuracy of 89.42%,an average AUC of 0.9356,and an average F1 score of 72.85%,outperforming the other 4 automatic ECG diagnosis models.Additionally,ablation study further validates the effectiveness of BiMamba block.It is demonstrated that the proposed model has a high precision in the multi-label classification for 12-lead long-term ECG signals.

Objective·To investigate the effect of early postoperative administration of zoledronic acid on fracture healing and functional recovery in elderly patients with osteoporotic femoral intertrochanteric fracture treated with proximal femoral nail antirotation(PFNA)surgery,and explore other potential prognostic factors.Methods·A total of 174 patients with femoral intertrochanteric fractures of 80 years old or above who underwent PFNA treatment in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from January,2016 to February,2022,were divided into experimental group(n=26)and control group(n=148)according to whether they received zoledronic acid early after surgery.All patients were followed up twice at 6 weeks and 12 weeks after surgery.The patients in the experimental group were matched with the control group by propensity score matching(PSM)at a ratio of 1:3(the matching factors included age,gender,fracture type,and body mass index).General characteristics,as well as fracture healing and functional recovery at the two follow-up visits were compared between the two groups after matching.Subsequently,Logistic regression was used to explore the potential prognostic factors on fracture healing at 12 weeks after surgery.Results·PSM resulted in 25 patients in the experimental group and 65 patients in the control group,and there were no statistically significant differences in baseline characteristics between the two groups.The fracture healing rates at 6 weeks and 12 weeks after surgery in the experimental group(16.0%and 96.0%,respectively)were higher than those in the control group(1.5%and 73.8%),and the differences were statistically significant(P<0.05).Harris hip function score in the experimental group at 12 weeks was significantly higher than that of the control group(P=0.019).The results of Logistic regression analysis showed that good surgical reduction(OR=12.52,95%CI 2.67?58.74,P=0.001),early postoperative administration of zoledronic acid(OR=10.14,95%CI 1.01?102.09,P=0.049),and higher serum albumin level(OR=1.15,95%CI 1.02?1.29,P=0.025)were the favorable factors of early fracture healing,while unstable fracture(OR=0.10,95%CI 0.03?0.31,P=0.000)was the unfavorable factor.Conclusion·For elderly patients with osteoporotic intertrochanteric femoral fractures treated with PFNA surgery,early postoperative administration of zoledronic acid can promote fracture healing and lead to better functional recovery;in addition,good surgical reduction and higher serum albumin levels are favorable factors for fracture healing,whereas unstable fracture presents as a hindrance to the healing process.

Acute pancreatitis often progresses rapidly, and if it is not controlled in time, it may lead to multiple organ injury and even death due to organ failure. At present, there is still a high proportion of patients with acute pancreatitis who died due to liver failure. The liver and the pancreas are interrelated physiologically and affect each other pathologically. This article elaborates on the molecular mechanism of liver injury in acute pancreatitis from the six aspects of the physiological relationship between the pancreas and the liver, cytokines, inflammatory response, oxidative stress, microcirculation disturbance, and intestinal flora translocation.

Metabolic disorders are observed in women after menopause, and the postmenopausal women suffering from chronic liver diseases have an increased risk of progression to liver fibrosis, with a higher risk than male patients of the same age, which may be associated with the decline of ovarian function and the reduction of estrogen level after menopause. This article summarizes the research advances in the molecular mechanism of progression to liver fibrosis from the aspects of estrogen and oxidative stress, activation of hepatic stellate cells, accumulation of extracellular matrix, and immune regulation. It is pointed out supplementation with an appropriate amount of estrogen in the perimenopausal period and the early menopausal period can reduce the risk of liver fibrosis and delay or even reverse the process of liver fibrosis, thereby improving quality of life and prolonging survival time in elderly female patients.

Objective: To evaluate the effect of hydrogen on the mitochondrial function in brain tissues of mice with sepsis-associated encephalopathy (SAE). Methods: Two hundred and sixty-eight healthy male C57 mice, aged 6 weeks, weighing 20-25 g, were divided into 4 groups (n=67 each) using a random number table method: sham operation group (group SH), sham operation plus hydrogen gas group (group SH+ H₂), group SAE, and SAE plus hydrogen gas group (group SAE+ H₂). Sepsis was produced by cecal ligation and puncture in anesthetized mice.The mice in group SH+ H₂ and group SAE+ H₂ inhaled 2% hydrogen gas for 1 h starting from 1 and 6 h after operation, respectively.The postoperative 7-day survival rate was recorded.Brain tissues were obtained at 24 h after operation to count the normal neurons in hippocampal CA1 region.At 6, 12 and 24 h after operation, hippocampal mitochondria were isolated for determination of mitochondrial membrane potential (MMP) by fluorescence spectrophotometry and ATP content by a bioluminescence assay.Y-maze (spontaneous alternation) test was performed at days 3, 5 and 7 after operation. Results: Compared with group SH, the 7-day survival rate was significantly decreased, the number of normal neurons in hippocampal CA1 region, MMP, mitochondrial ATP content and spontaneous alternation percentage in Y-maze test were significantly decreased in group SAE and group SAE+ H₂ (P<0.05). Compared with group SAE, the 7-day survival rate, the number of normal neurons in hippocampal CA1 region, MMP, mitochondrial ATP content and spontaneous alternation percentage in Y-maze test were significantly increased in group SAE+ H₂ (P<0.05). Conclusion The mechanism by which hydrogen reduces SAE is probably associated with improving mitochondrial function in brain tissues of mice.