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.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

Objective In order to address the issues of inconvenience,high medical costs,and lack of universality associated with traditional knee rehabilitation equipment,a portable intelligent wheelchair for knee rehabilitation was designed in this study.Methods Based on the analysis of the knee joint's structure and rehabilitation mechanisms,an electric pushrod-driven rehabilitation institution was developed.A multi-functional module was designed with a modular approach,and the control of the wheelchair body and each functional module was implemented using an STM32 single-chip microcomputer.A three-dimensional model was established using SolidWorks software.In conjunction with Adams and Ansys simulation software,kinematic and static analyses were conducted on the knee joint rehabilitation institution and its core components.A prototype was constructed to verify the equipment's actual performance.Results According to the prototype testing,the actual range of motion for the knee joint swing rod is 15.1°～88.9°,the angular speed of the swing rod ranges from-7.9 to 8.1°/s,the angular acceleration of the swing rod varies from-4.2 to 1.6°/s2,the thrust range of the electric pushrod is-82.6 to 153.1 N,and the maximum displacement of the load pedal is approximately 1.7 mm,with the leg support exhibiting a maximum deformation of about 1.5 mm.Conclusion The intelligent knee joint rehabilitation wheelchair meets the designed functions and its actual performance aligns with the design criteria,thus validating the rationality and feasibility of the structural design.

Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery, which has merits of biocompatibility, biodegradability and mild gelation conditions. However, its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity. Moreover, for the intracellularly acted proteins, cell membrane as a primary barrier hinders the transmembrane delivery of proteins. The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes. We herein develop a protease-manipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins. The embedded polymeric nanogels (CytoC/aNGs) preserve activity of cytochrome

Objective To develop a questionnaire on the professional needs of care for family caregivers of stroke survivors and test the reliability and validity. Methods Based on the family system theory and family support model, the first draft of questionnaire was formed through literature review and in-depth qualitative interview, and the test draft was formed through expert consultation and pre-experiment. The qualified caregivers in 5 community health service centers of Nanyang Road, linshanzhai, hanghai East Road, high tech Zone and Qinling Road in Zhengzhou from May to August 2018 were selected as the research objects for questionnaire survey. 240 valid questionnaires were selected and tested to form a formal questionnaire. Results The cumulative variance contribution rate of four common factors extracted by exploratory factor analysis was 67.343%, the overall Cronbach's α coefficient of the questionnaire was 0.919, the overall retest reliability was 0.914, the total content validity index (S-CVI) was 0.98, the content validity index (I-CVI) of each item was above 0.80, the correlation coefficient between each item and the total score of the questionnaire was 0.424-0.652, and the correlation coefficient between each dimension was 0.127-0. 566, the correlation coefficient between each dimension and total score was 0.592-0.785, the formal questionnaire included 4 dimensions and 29 items. Conclusions The questionnaire has good reliability and validity,which can be used to evaluate the professional care needs of home-based stroke caregivers.

Objective To evaluate the safety and efficacy of transplantation of purified CD34 + cells (PCCs) in treatment of critical limb ischemia (CLI) caused by thromboangiitis obliterans (TAO).Methods From May 2009 to June 2015,34 TAO-induced-CLI cases underwent PCCs transplantation.None of these patients were eligible for surgical or endovascular revascularization.G-CSF was subcutaneously injected for 5 days before peripheral CD34 + cells were isolated,purified and intramuscularly injected in the limbs.Patients were regularly follow-up.Results Technical success was achieved in all cases.The mean number of transplanted cells was (7.5 ± 2.4) × 105/kg.The follow-up was accomplished in 32 cases,ranging from 6 to 79 months (mean 45 ±24 months),and two patients were lost.Wong-Baker FACES pain rating scale score significantly decreased from 8.0 ±2.0(4-10)to 2.2 ±3.1 (P ＜0.05) at 1 month.The Peak pain-free walking time improved from (4.0 ± 2.0) min to (13.5 ± 5.3) min (P ＜ 0.05) at 3 months and (19.0 ± 3.1) min (P ＜ 0.05) at 6 months.The ankle-brachial index increased from 0.42 ± 0.20 to 0.50 ± 0.10 (P ＜ 0.05) at 3 months and 0.52 ± 0.11 (P ＜ 0.05) at 6 months,respectively.Transcutaneous partial oxygen pressure rose from (25 ± 11) mmHg to (48 ± 11) mmHg(P ＜ 0.05) at 3 months and (58 ± 10) mmHg (P ＜ 0.001) at 6 months,respectively.Ulcers healed in 21 out of 22 patients at (5 ± 4) months.The overall amputation-free survival rate was 94.1％ at 6 months and 91.2％ at 48 months.No major adverse events were observed perioperatively or postoperatively.Conclusions Transplantation of PCCs could yield safe,satisfactory and durable treatment outcomes in patients with TAO-induced-CLI.

Objective To evaluate the application of SOLIS in the surgery on anterior intervertebral fusion for the treatment of traumatic cervical disc protrnsion. Methods 53 traumatic single segment cervical disc protrusion were divided into three groups randomly. The A group (SOLIS) :n=18, SOLIS filled with autocancellous bone were implanted between the cervical vertebrae. The B group(Syncage) :n =16, as the first group Syncage filled with auto-cancellous bone were implanted. The C group:n=19,anterior cervical decompression and fusion with bone autograft and internal fixation with ACPS. The operations of the surgery on anterior cervical decompression in three groups were the same. Recovery of nerve function was observed by JOA score and the fusion state, stability and changes of interver-tebra height of fusion segment were evaluated by X ray. Results The average duration of the follow-up was 16.5 months in 53 cases. Bony fusion could be found 3～9months after operation in all cases. In all A (SOLIS) group cases,the movement of the implanted $OLIS Cage were not found. The heights of the cervical intervertebral spaces and the physiological curvature were restored without loss in the duration of follow-up. The average JOA was(10.4±2.4) be-fore operation and(14.9±2.0)after operation. There was highly significant variation between the former and the latter (P<0.01). In the B (Syncage)group,5 cases had cage subsidence, therefore the height of intervertebra and the phys-iological curvature were lost. The average JOA was (10.6±2.5) before operation and (13.2±2.3) after operation.There was significant variation between the former and the latter(P<0.05). In the C group the third group, the move-ment of the fixed titanium plate were not found in the duration of follow-up in 18 cases. The titanium plate fixation was loose in 1 case. The average JOA was(10.5±2.4) bofore operation and(15.1±1.9) after operation. There was high-ly significant variation between the former and the latter(P<0.01). After operation,there was significant difference in the JOA score between the A group and the B group,between the C group and the B group(P<0.05) ,and there was no difference between the A group and the C group(P>0.05). Conclusion Treatment of single segment prolapse of the cervical intervertebral disc with SOLIS cage has some advantages such as higher fusion rate, higher recovery rate of nerve function and low rate of loss of intervertebra] height.