Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective:To explore the efficacy and safety of sivelestat sodium in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU).Methods:Sixty patients with ARDS admitted to the ICU of the Fuyang Hospital Affiliated to Anhui Medical University from August 1, 2023 to November 1, 2024 were selected and divided into the control group (conventional treatment, 30 cases) and the sivelestat sodium group (treated with sivelestat sodium in addition to conventional treatment, 30 cases) by the random number table method. The clinical data such as inflammatory factors, blood gas analysis indicators, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score of the two groups of patients before treatment and 3 days after treatment were compared. The prognostic indicators such as mechanical ventilation time, ICU stay time, total hospital stay time, 28-day mortality rate and clinical efficacy of the two groups of patients were compared.Results:Before treatment, there were no statistically significant differences in inflammatory factors, blood gas analysis indicators, APACHE Ⅱ score and SOFA score between the two groups of patients (all P>0.05). After 3 days of treatment, the improvement degrees of APACHE Ⅱ score, SOFA score, arterial partial pressure of oxygen (PaO 2), oxygenation index (PaO 2/FiO 2), procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) in the sivelestat sodium group were all greater than those in the control group. The differences were all statistically significant (all P<0.05); The mechanical ventilation time [(5.31±4.12) d vs (7.17±2.32)d] and ICU stay [(6.31±3.42)d vs (8.93±5.26)d] of patients in the sivelestat sodium group were significantly shorter than those in the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference in the 28-day mortality rate between the sivelestat sodium group [20.00%(6/30)] and the control group [43.33%(13/30)] ( P>0.05). The total effective rate of treatment in the sivelestat sodium group was significantly higher than that in the control group [80.00%(24/30) vs 56.67%(17/30)], and the difference was statistically significant (χ 2=4.167, P=0.041). Conclusions:Sivelestat sodium is helpful in improving the physiological parameters of patients with ARDS, effectively reducing the levels of inflammatory factors in the body, shortening the duration of mechanical ventilation and ICU stay, but has no significant effect on the 28-day mortality rate.

Objective:To explore the efficacy and safety of sivelestat sodium in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU).Methods:Sixty patients with ARDS admitted to the ICU of the Fuyang Hospital Affiliated to Anhui Medical University from August 1, 2023 to November 1, 2024 were selected and divided into the control group (conventional treatment, 30 cases) and the sivelestat sodium group (treated with sivelestat sodium in addition to conventional treatment, 30 cases) by the random number table method. The clinical data such as inflammatory factors, blood gas analysis indicators, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score of the two groups of patients before treatment and 3 days after treatment were compared. The prognostic indicators such as mechanical ventilation time, ICU stay time, total hospital stay time, 28-day mortality rate and clinical efficacy of the two groups of patients were compared.Results:Before treatment, there were no statistically significant differences in inflammatory factors, blood gas analysis indicators, APACHE Ⅱ score and SOFA score between the two groups of patients (all P>0.05). After 3 days of treatment, the improvement degrees of APACHE Ⅱ score, SOFA score, arterial partial pressure of oxygen (PaO 2), oxygenation index (PaO 2/FiO 2), procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) in the sivelestat sodium group were all greater than those in the control group. The differences were all statistically significant (all P<0.05); The mechanical ventilation time [(5.31±4.12) d vs (7.17±2.32)d] and ICU stay [(6.31±3.42)d vs (8.93±5.26)d] of patients in the sivelestat sodium group were significantly shorter than those in the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference in the 28-day mortality rate between the sivelestat sodium group [20.00%(6/30)] and the control group [43.33%(13/30)] ( P>0.05). The total effective rate of treatment in the sivelestat sodium group was significantly higher than that in the control group [80.00%(24/30) vs 56.67%(17/30)], and the difference was statistically significant (χ 2=4.167, P=0.041). Conclusions:Sivelestat sodium is helpful in improving the physiological parameters of patients with ARDS, effectively reducing the levels of inflammatory factors in the body, shortening the duration of mechanical ventilation and ICU stay, but has no significant effect on the 28-day mortality rate.

To study the technical principles and case analysis of typical fault of fully automatic enzyme-linked immunosorbent assay(ELISA)analyzer,in order to improve the usage effect of the analyzer.The microparticle enzyme immunoassay(MEIA)analysis technique was used to complete the ELISA test.The main calibration,standard calibration,qualitative calibration and calibration solution correction were used as the calibration methods of the ELISA analyzer to improve the analytic precision of ELISA.By analyzing the cases of typical faults encountered during the use of the fully automatic ELISA analyzer,such as washing machine,startup initialization alarm,boot disk,sampling arm and filter,the corresponding solutions of fault were proposed to provide reference for the maintenance and management of the fully automatic ELISA analyzer at later stage.

Objective To explore the relationship between preoperative coronary angiography and postoperative acute kidney injury (AKI) in cardiac surgery. Methods The clinical data of patients who underwent coronary angiography within 30 days before cardiac surgery in the First Affiliated Hospital of Xi’an Jiaotong University from January 2015 to April 2019 were retrospectively analyzed. Univariate analysis and multivariate logistic regression analyses were used to explore the relationship between the interval from preoperative coronary angiography to cardiac surgery and postoperative AKI. Results Finally 1 112 patients were collected, including 700 males and 412 females, with a median age of 61 (55, 66) years. The incidence of postoperative AKI was 40.8% (454/1 112), of which grade 2-3 AKI accounted for 11.9%. Multivariate analysis showed that age (OR=1.049, 95%CI 1.022-1.077, P<0.001), body mass index (OR=1.065, 95%CI 1.010-1.123, P=0.020) and time interval between preoperative coronary angiography and cardiac surgery within 24 hours (OR=1.625, 95%CI 1.116-2.364, P=0.011) were independent predictors of postoperative AKI. Patients who underwent coronary angiography within 24 hours before surgery had a 10.6% higher incidence of postoperative AKI compared to those who underwent angiography ≥24 hours before surgery (P=0.004). Patients who underwent valve surgery with or without coronary artery bypass grafting (CABG) had a higher risk of AKI than those who only underwent CABG. The in-hospital stay of patients who developed AKI was 2 days longer than those without AKI. However, undergoing coronary angiography within 24 hours before cardiac surgery did not prolong the length of ICU stay or hospital stay, nor did it increase the risk of death or renal failure after the operation. Conclusion Undergoing coronary angiography within 24 hours before cardiac surgery increases the risk of postoperative AKI.

Objective:To preliminarily investigate the correlation between right atrial and right ventricular myocardial strain, assessed by two-dimensional speckle-tracking echocardiography (2D-STE), and early death in patients after left ventricular assist device (LVAD) implantation.Methods:A total of 39 patients with end-stage heart failure who underwent LVAD implantation were prospectively included in the First Affiliated Hospital of Xi′an Jiaotong University from April 2022 to March 2024. Routine transthoracic echocardiography (TTE) images were obtained within 3 days before LVAD implantation for all patients to comprehensively assess left ventricular and right ventricular function. The right ventricular free wall longitudinal strain (RVFWSL), right ventricular four-chamber longitudinal strain (RV4CSL), right atrial reservoir strain (RASr), conduit strain (RAScd), and contraction strain (RASct) were measured by using 2D-STE. The primary endpoint was early postoperative mortality. The patients were divided into survival group and death group based on whether died within 3 months after LVAD implantation.Results:Of all the patients, five cases died in hospital after LVAD implantation, with 4 deaths attributed to right heart failure and 1 death to malignant arrhythmia. The RVFWSL and RV4CSL (absolute values) in the death group were significantly lower than those in the survival group (both P<0.05). Cox multivariate regression analysis showed that RVFWSL and RV4CSL were risk factors for death within 3 months [ HR: 0.521(95% CI=0.275-0.986), P=0.045; HR: 0.491(95% CI=0.252-0.958), P=0.037]. Further ROC curve analysis revealed that the diagnostic cutoff value for RVFWSL in predicting death within 3 months was ≤|-12.1|%, with the area under the curve (AUC) of 0.938(0.812-0.990), and the diagnostic cutoff value for RV4CSL was ≤|-14.2|%, with an AUC of 0.926(0.796-0.985). Conclusions:In patients with end-stage heart failure, RVFWSL ≤ |-12.1|% and RV4CSL ≤ |-14.2|% are associated with an increased risk of death within 3 months after LVAD implantation.

Objective:To preliminarily investigate the correlation between right atrial and right ventricular myocardial strain, assessed by two-dimensional speckle-tracking echocardiography (2D-STE), and early death in patients after left ventricular assist device (LVAD) implantation.Methods:A total of 39 patients with end-stage heart failure who underwent LVAD implantation were prospectively included in the First Affiliated Hospital of Xi′an Jiaotong University from April 2022 to March 2024. Routine transthoracic echocardiography (TTE) images were obtained within 3 days before LVAD implantation for all patients to comprehensively assess left ventricular and right ventricular function. The right ventricular free wall longitudinal strain (RVFWSL), right ventricular four-chamber longitudinal strain (RV4CSL), right atrial reservoir strain (RASr), conduit strain (RAScd), and contraction strain (RASct) were measured by using 2D-STE. The primary endpoint was early postoperative mortality. The patients were divided into survival group and death group based on whether died within 3 months after LVAD implantation.Results:Of all the patients, five cases died in hospital after LVAD implantation, with 4 deaths attributed to right heart failure and 1 death to malignant arrhythmia. The RVFWSL and RV4CSL (absolute values) in the death group were significantly lower than those in the survival group (both P<0.05). Cox multivariate regression analysis showed that RVFWSL and RV4CSL were risk factors for death within 3 months [ HR: 0.521(95% CI=0.275-0.986), P=0.045; HR: 0.491(95% CI=0.252-0.958), P=0.037]. Further ROC curve analysis revealed that the diagnostic cutoff value for RVFWSL in predicting death within 3 months was ≤|-12.1|%, with the area under the curve (AUC) of 0.938(0.812-0.990), and the diagnostic cutoff value for RV4CSL was ≤|-14.2|%, with an AUC of 0.926(0.796-0.985). Conclusions:In patients with end-stage heart failure, RVFWSL ≤ |-12.1|% and RV4CSL ≤ |-14.2|% are associated with an increased risk of death within 3 months after LVAD implantation.

Objective Analysis of misdiagnosis and causes of neck pain related diseases,and to explore the different diagnostic ideas of Chinese and Western medicine and the countermeasures to reduce misdiagnosis,so as to help acupuncturists improve their understanding of this disease.Method The relevant literature on conditions with neck pain as the chief complaint was systematically searched,using data mining for retrospective analysis,sorting out the different diagnostic ideas of Chinese and Western medicine,proposing individualized countermeasures for reducing misdiagnosis.Results ①After retrieval,126 case reports were included,totaling 445 cases of diagnostic error,involving 9 systems and 38 conditions,of which cervical spondylosis was the most commonly misdiagnosed.The confirmed cases involved 7 systems and 46 conditions,of which tumors,subacute thyroiditis,eagle syndrome,acute myocardial infarction and thoracic outlet syndrome were the most commonly misdiagnosed.②The are various causes for the misdiagnosis of this condition,including atypical symptoms,insufficient understanding of the condition,lack of understanding of rare conditions,incomplete physical and auxiliary examina-tions,or wrong guidance.③There are many erroneous diagnosis of neck pain,which can delay the condition and even endanger lives.A clear diagnosis is the premise and basis for effective Traditional Chinese and Western medical intervention.Conclusion There exists a number of possibilities for the misdiagnosis of this disease.Therefore,we must meticulously collect medical history,improve specialist physical and auxiliary examination,emphasizing holistic thinking and differential diagnosis.Acupuncture department as the main department of patients with neck pain,in order to improve the level of diagnosis and treatment of neck pain,requires acupuncturists to consolidate the Western medicine diagnosis of neck pain,closely linked to the Traditional Chinese Medicine"three principles"of"treatment based on disease differentiation",in order to reduce misdiagnosis,cure the disease,improve long-term efficacy.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.