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 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.

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.

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.

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.

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.

Objective: To observe the effects of electroacupuncture (EA) pretreatment on motor function, cerebral blood flow, cerebral infarction volume, and vascular endothelial growth factor (VEGF) level in middle cerebral artery occlusion (MCAO) model rats. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into a normal group, a model group, and an EA group, with eight rats in each group. The middle cerebral artery ischemia-reperfusion model was established by the suture-occluded method in the model group and the EA group, while not in the normal group. The EA group was pretreated with EA at bilateral Fengchi (GB20) before model preparation, once a day for 30 min each time for a total of 7 d. The changes in the CatWalk gait parameters, modified Bederson neurological deficit score, cerebral blood flow, cerebral infarction volume after ischemia, and VEGF level in the brain tissue of rats in each group were observed. Results: Compared with the normal group, the modified Bederson neurological deficit score in the model group and the EA group increased after modeling (P<0.05), and the CatWalk gait parameters (one-leg stance duration, gait cadence, and gait cycle) were all changed (P<0.05). Compared with the model group, the modified Bederson neurological deficit score in the EA group decreased (P<0.05), and the CatWalk gait parameters improved (P<0.05). Immediately after ischemia, the cerebral blood flow in the normal group was greater than that in the model group and the EA group (P<0.05); after reperfusion, the cerebral blood flow in the EA group was greater than that in the model group (P<0.05). Compared with the normal group, the cerebral infarction volume in the model group and the EA group increased (P<0.05). Compared with the model group, the cerebral infarction volume in the EA group decreased (P<0.05). The expression level of VEGF-positive cells in the rat brain tissue in the model group was higher than that in the normal group (P<0.05), and was higher in the EA group than in the model group (P<0.05). Conclusion: EA pretreatment improves the limb motor function in MCAO model rats, alleviates the symptoms of neurological deficits, promotes the recovery of cerebral blood flow, reduces the cerebral infarction area after MCAO modeling, and increases the VEGF expression in the brain tissue.

OBJECTIVE：To study the protective effects of butein on oxidative stress injury of PC12 cell and its effects on mitochondrial function. METHODS：Rats PC12 cells were divided into normal control group，model group，solvent control group（1 ‰ dimethyl sulfoxide），butein high，medium and low concentration groups（2，1，0.5 μmol/L）. The latter 4 groups were given relevant reagent/medicine for intervention；24 h later，other groups were given 100 mU/mL glucose oxidase to induce oxidant stress model except for normal control group. After 4 h culture，cell survival rate，apoptosis rate，the levels or activities of ROS，MDA，SOD，CAT，GSH-Px，ATP，IL-1β and TNF-α as well as the change of MMP were detected. RESULTS：Compared with normal control group，cell survival rate，the levels or activities of SOD，CAT，GSH-Px and ATP were all decreased significantly，and apoptotic rate，the content of ROS，the levels of MDA，IL-1β and TNF-α were all increased significantly（P＜0.05 or P＜0.01），while the MMP was decreased significantly. Compared with model group，above indexes of solvent control group had no significant change （P＞0.05），cell survival rates，the levels or activities of SOD （except for medium and low concentration groups），CAT，GSH-Px（except for medium and low concentration groups），ATP（except for low concentration group）were increased significantly in butein high，medium and low concentration groups，while apoptotic rates，the content of ROS，the levels of MDA，IL-1 β and TNF-α were decreased significantly（P＜0.05 or P＜0.01），while the MMP were increased significantly. CONCLUSIONS：Butein can increase the antioxidant enzyme activity， stabilize mitochondrial function， inhibit oxidative stress and inflammationthus， increase energy generation inhibiting neuronal cell apoptosis ultimately exerting a neuroprotective effect.

Objective To summarize the computed tomographic (CT) manifestations of pulmonary aspergillosis after organ transplantation and compare different signs between pulmonary aspergillosis and bacterial pneumonia.Methods CT images of pulmonary aspergillosis (n =62) and bacterial pneumonia (n =68) in post-transplantation patients were reviewed.The signs were categorized with consolidation,mass,large nodule (≥1crn),small nodule and bud-in-tree pattern.Some detailed useful differentiating signs such as halo sign,air bronchogram sign,reversed halo sign,hypodensity sign and cavitation were also analyzed.Results CT patterns of pulmonary aspergillosis included consolidation,mass,large nodule,small nodule and bud-in-tree pattern.The most common was large nodule (75.8％),followed by consolidation (48.4％)and mass (29.0％).And small nodule (16.1 ％) and bud-in-tree (12.9％) patterns were concurrent.For consolidation pattern,the proportion of bacterial pneumonia (69.1％) was the larger;For mass pattern,the proportion of pulmonary aspergillosis (29.0％) was the larger.For large nodule pattern,there was no difference.The detail sign of large nodule in two groups had no difference In detailed signs of consolidation pattern,air bronchogram sign was more often seen in bacterial pneumonia while cavitation was more frequently found in pulmonary aspergillosis.In detailed signs of mass pattern,pulmonary aspergillosis often has single lesion (66.7％),cavitation (83.3％)and air crescent sign (77.8％) is more common.The proportion of halo sign was 30.7％.Conclusions CT manifestations of pulmonary aspergillosis are diverse after organ transplantation.There is some difference and yet overlap with bacterial pneumonia.

The study aims to use CRISPR/Cas9 introducing foreign gene targeted knock-in into chicken EAV-HP genome. First, specific primers were designed for amplification of EAV-HP left, right homologous arms and enhanced green fluorescent protein (eGFP) expression cassette. PCR products of homologous arms were ligated to both sides of eGFP by overlap extension PCR, resulting in full-length donor DNA fragment designated as LER. Then LER fragments were cloned into pMD19-T to obtain donor vector pMDT-LER. Subsequently, the donor vector pMDT-LER was transfected into HEK293T cells to verify the expression of eGFP gene. Furthermore, co-transfection of CRISPR/Cas9 expression vector and pMDT-LER into chicken DF-1 cells was performed to achieve eGFP transgenic cells. Meanwhile, eGFP expression was observed in cells, and the event of eGFP integration into EAV-HP genome was detectable by amplification of target DNA. Finally, the transgenic DF-1 cells were passaged seven times, and the stable integration and expression of eGFP was checked by PCR and Western blotting. These results demonstrated that eGFP gene was knocked into the EAV-HP genome successfully, which provides a new integration site for research of transgenic chicken.
Animals ; CRISPR-Cas Systems ; Chickens ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Knock-In Techniques ; Genome ; HEK293 Cells ; Humans