Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Objective To investigate the role of Kelch-like-epichlorohydrin-associated protein 1/nuclear factor erythroid-derived factor-2-related factor 2(Keap1-Nrf2)and nuclear factor-κB(NF-κB)signaling pathways in sepsis-associated encephalopathy(SAE).Methods Male C57BL/6J mice of SPF were randomly divided into four groups(n=10):the control group and LPS 6 h,24 h and 48 h groups.The behavioral changes of the mice were assessed based on their general conditions and open field test(OFT).ELISA was used to measure the levels of pro-inflammatory cytokines in mouse serum,and the antioxidant capacity assay kit to examine antioxidant activity in brain tissues of mice.Real-time quantitative PCR(qPCR)was adopted to detect the mRNA levels of toll-like receptor4(Tlr4),NF-κB,Keap1 and Nrf2 in the hippocampus,and to determine protein expressions of NF-κB a Nrf2、Keap1 and Tlr4 with Western blotting.Results Compared to the control group,the serum concentrations of interleukin 6(IL-6)in lipopolysaccharide(LPS)groups increased at 6 h,and reached the peak at 24 h and 48 h(P＜0.01).The levels of serum interleukin 18(IL-18)in the LPS groups increased significantly at 6 h and 24 h(P＜0.01)but there was no statistically significant difference compared with the 48h group.The results indicated the activity of superoxide dismutase(SOD)and glutathione(GSH)in brain tissues in LPS groups increased(P＜0.01).OFT results showed the time spent in the center of the open field,the distance covered around the center,and total distance covered by mice in LPS groups were significantly reduced(P＜0.01),except for the time spent in the center of the open field in the LPS 24 h group.The mRNA expressions of Tlr4 and(LPS 6 h,48 h)NF-κB in the hippocampus tissue of mice in LPS groups were elevated(P＜0.05),so were the mRNA expressions of Keap1 and Nrf2 in LPS 6 h group.Additionally,the protein expressions of NF-κB,Keap1 and Tlr4 increased in LPS groups,so did the protein expression of Nrf2 in LPS 24 h and 48 h groups(P＜0.05).Conclusion Keap1-Nrf2 and NF-κB signaling pathways may play a certain role in SAE.

Objective To analyze the characteristics and epidemic trends of Mycoplasma pneumoniae(MP)infection among the pa-tients in our hospital,and explore the diagnostic values of interleukin-6(IL-6)and procalcitonin(PCT)detection for MP infection.Methods A retrospective analysis was conducted on the test results of MP nucleic acid and clinical data,including age,gender,sam-pling date,and treatment category of the 1 122 pneumonia patients in our hospital from September 1,2022,to August 31,2023.The positive detection rate of MP nucleic acid was analyzed in different genders,ages,visit categories,and seasons.Receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic value of IL-6 and PCT levels,and their ratio values in Mycoplasma pneumoniae pneumonia(MPP).Results Among the 1 122 pneumonia patients,the overall positive detection rate of MP was 24.96％.The positive detection rates of MP nucleic acid in male and female patients were 23.28％and 27.29％,respectively,with no statistical-ly significant difference(P＞0.05).The median age of MP nucleic acid-negative patients was 37 years,while that of MP nucleic acid-positive patients was 7 years,showing a statistically significant difference(P＜0.01).MP nucleic acid-positive patients were mainly concentrated in the age groups of 1 to 2 years(20.37％),3 to 5 years(25.60％),and 6 to 8 years(67.40％).The positive detection rates of MP nucleic acid among 913 inpatients and 209 outpatients were 22.45％and 35.89％,respectively,with statistically significant difference(P＜0.01).The highest MP nucleic acid positive detection rate was observed in autumn(42.47％).MP could be co-infected with five other respiratory pathogens in which human rhinovirus(HRV)was the most common(17 cases).ROC curve analysis showed that the IL-6/PCT ratio had the best diagnostic performance for MP infection in the patients with all ages,with an area under the curve(AUCROC)of 0.746,superior to IL-6 and PCT alone.For MP-susceptible patients aged 6 to 8 years,IL-6 had the highest predictive value for MP infection,with an AUCROC of 0.767.Conclusions MPP tends to be epidemic in autumn,with children aged 6 to 8 years being the main susceptible population.The IL-6/PCT ratio is expected to become an auxiliary diagnostic and prognostic evaluation indi-cator for MPP.IL-6 levels have the highest predictive value for MP infection in the susceptible population.

Objective To investigate the clinical significance of serum S100 calcium binding protein(S100 A4)and S100A12 in patients with severe traumatic brain injury(sTBI).Methods A total of 147 sTBI pa-tients admitted to Handan Central Hospital from March 2021 to March 2023 were selected as the sTBI group,and 50 healthy subjects who underwent physical examination in Handan Central Hospital during the same pe-riod were selected as the control group.The correlation between S100A4,S100A12 levels and brain injury markers and the influencing factors of early death in sTBI patients were analyzed,and the predictive value of serum S100A4 and S100A12 for early death in sTBI patients was studied.Results The serum levels of S100A4,S100A12,myelin basic protein(MBP),S100B and neuron specific enolase(NSE)in sTBI group were significantly higher than those in control group(P＜0.05).The serum levels of S100A4 and S100A12 were positively correlated with MBP,NSE and S100B in sTBI patients(P＜0.05).Multivariate Logistic regression analysis showed that decreased Glasgow coma scale(GCS)score on admission and increased serum levels of S100A4,S100A12,MBP,NSE and S100B were risk factors for early death in sTBI patients(P＜0.05).Receiv-er operating characteristic curve showed that the combination of serum S100A4 and S100A12 with GCS score,MBP,NSE and S100B was superior to any single detection in predicting early death in sTBI patients.Conclu-sion The serum levels of S100A4 and S100A12 are increased in sTBI patients,which are related to the aggra-vations of brain injury and early death.The combined detection of S100A4 and S100A12 has a good predictive value for early death in sTBI patients.

Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.

Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

Objective:To explore the surgical strategies and clinical efficacy for aortic dissection combined with refractory superior mesenteric artery (SMA) ischemia.Methods:This is a retrospective case series study. Clinical data of 24 patients with aortic dissection and refractory SMA ischemia admitted to the Department of Vascular Surgery, Zhongshan Hospital, Fudan University from August 2010 to August 2020 were retrospectively collected. Of the 24 patients, 21 were males and 3 were females, with an age of (50.3±9.9) years (range: 44 to 72 years).Among them, 9 cases were Stanford type A aortic dissection, and 15 cases were type B. All patients underwent CT angiography upon admission, and based on imaging characteristics, they were classified into three types. Type Ⅰ: severe stenosis/occlusion of the SMA true lumen only; Type Ⅱ: stenosis of the true lumens in the descending aorta and SMA (isolated type); Type Ⅲ: stenosis of the true lumens in the thoracoabdominal aorta and SMA (continuation type). Surgical procedures, complications, mortality, and reintervention rates were recorded.Results:Among the 24 patients, 17 (70.8%) were classified as Type Ⅰ, 4 (16.7%) as Type Ⅱ, and 3 (12.5%) as Type Ⅲ. Fourteen cases of Type Ⅰ underwent thoracic endovascular aortic repair combined with SMA stent implantation. Additionally, 3 Type Ⅰ and 1 Type Ⅱ patients underwent only SMA reconstruction (with one case of chronic TAAD treated with iliac artery-SMA bypass surgery). Moreover, 3 Type Ⅱ and 3 Type Ⅲ patients underwent descending aorta combined with SMA stent implantation. There were 5 patients (20.8%) who underwent small bowel resection, either in the same sitting or in a staged procedure. During hospitalization, 4 patients died, resulting in a mortality rate of 16.7%. Among these cases, two patients succumbed to severe intestinal ischemia resulting in multiple organ dysfunction syndrome. The follow-up duration was (46±9) months (range: 13 to 72 months). During the follow-up, 2 patients died, unrelated to intestinal ischemia. The 5-year freedom from reintervention survival rate was 86.1%, and the 5-year cumulative survival rate was 82.6%.Conclusions:Patients with aortic dissection and refractory SMA ischemia have a high perioperative mortality. However, implementing appropriate surgical strategies according to different clinical scenarios can reduce mortality and alleviate intestinal ischemia.

Objective:To evaluate the clinical outcomes of thoracic endovascular aortic repair (TEVAR) in the treatment of Stanford type B aortic dissection (TBAD) in Marfan syndrome patients who had no history of aortic arch replacement.Methods:This is a retrospective case-series study. From January 2009 to December 2019,the clinical data of Marfan syndrome patients who underwent TEVAR for TBAD at the Department of Vascular Surgery were collected. A total of 23 patients were enrolled,including 15 males and 8 females. The age was (38.0±11.0) years (range:24 to 56 years). Among them,12 patients had history of ascending aortic surgery. Details of TEVAR,perioperative complications and reintervention were recorded and survival rate was analyzed by Kaplan-Meier curve.Results:Technical success was 91.3% (21/23). Two patients with technical failure were as follows:one patient had type Ⅰa endoleak at the completion angiography,which healed spontaneously during the follow-up,and the other patient suffered aortic intimal intussusception after the deployment of the first stent-graft, and the second stent-graft was deployed. However, type Ⅲ endoleak was detected,which disappeared during the follow-up. One patient died during hospitalization. The median follow-up time ( M(IQR)) was 60 (48) months (range:12 to 132 months). Reintervention was performed on 7 patients,including 3 distal stent-graft-induced new entry,2 distal aortic dilation,1 Ⅰa endoleak and 1 retrograde type A aortic dissection,respectively. Five-year cumulative survival rate was 86.7% (95% CI:86.6% to 86.8%) and the 5-year freedom from reintervention rate was 81.8% (95% CI:61.8% to 92.8%). Conclusions:TEVAR is feasible in the treatment of TBAD in Marfan syndrome patients who has no history of aortic arch replacement. It has high technical success rate and low perioperative complication.

Objective:To investigate the efficacy of 99Tc m-pyrophosphate (PYP) SPECT imaging for the differential diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA) and hypertrophic cardiomyopathy (HCM). Methods:Data of patients who were definitively diagnosed with ATTR-CA (35 patients (28 males, 7 females); age 62.5(58.6, 64.3) years) or HCM (14 patients (13 males, 1 female); age 60.5(57.3, 68.7) years) by extracardiac biopsy and echocardiography in the Second Xiangya Hospital of Central South University between June 2020 and March 2023 were retrospectively analyzed. All patients underwent planar and SPECT imaging 1 h after injection of 370-720 MBq 99Tc m-PYP. Visual scoring was performed (0-1 was negative, 2-3 was positive), and heart-to-contralateral lung uptake ratio (H/CL) was calculated based on planar images. The χ2 test was used to compare the difference in visual scores between ATTR-CA and HCM groups, and the diagnostic efficacy of the visual score was calculated. The H/CL differences between ATTR and HCM groups were compared with Mann-Whitney U test, and the ROC curve was used to analyze the efficacy of H/CL for the differential diagnosis of ATTR-CA and HCM. Results:There were 34 patients with visual scores≥2 and 1 patient with visual score<2 in the ATTR-CA group, 6 patients with visual scores =2 and 8 patients with visual scores <2 in HCM group, and there were significant differences between the 2 groups ( χ2=16.20, P<0.001). The diagnostic sensitivity of the visual score was 97.1%(34/35), and the specificity was 8/14. The H/CL in the ATTR-CA group was significantly higher than that in the HCM group (2.08(1.97, 2.20) vs 1.26 (1.17, 1.35), z=-5.09, P<0.001). The ROC curve analysis suggested that the optimal cut-off value was 1.45 (AUC: 0.980, 95% CI: 0.946-1.000; P<0.001); the sensitivity of H/CL differential diagnosis between HCM and ATTR-CA was 97.1%(34/35), and the specificity was 14/14. Conclusion:99Tc m-PYP SPECT imaging is useful in differentiation of ATTR-CA and HCM, and the optimal cut-off value of H/CL for differential diagnosis of these 2 diseases is 1.45.