Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

BACKGROUND: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database. PATIENTS AND METHODS: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021. High-risk patients were defined by ≥4 positive axillary lymph nodes, or 1-3 positive lymph node(s) with at least one high-risk feature (histologic grade 3, tumor size ≥5 cm, or Ki-67 ≥20%). A low-risk cohort included patients not meeting the criteria. Survival analysis was conducted with a cutoff of September 2021. RESULTS: The study included 4088 eligible patients (1310 high-risk patients and 2778 low-risk patients). High-risk patients were more likely to receive adjuvant chemotherapy and radiotherapy compared to low-risk patients. From 2013 to 2021, an increasing proportion of patients received aromatase inhibitors and ovarian function suppression as part of their AET. The 2-, 5-, and 7-year invasive disease-free survival for high-risk cohort were 90.67%, 75.26%, and 57.10%, respectively, these rates were notably higher for low-risk cohort at 97.14%, 89.85%, and 84.83%. High-risk patients demonstrated a higher risk of recurrence or death compared with low-risk patients (hazard ratio, 2.38; 95% CI, 1.82-3.12). CONCLUSION: In the setting of standard or even intensive AET, patients with EBC with high-risk features still present high recurrence risk, highlighting the urgent need for innovative adjuvant treatment strategies.

Spotlight on ideal target antigens and resistance in antibody-drug conjugates: Strategies for competitive advancement.

Antibody-drug conjugates (ADCs) represent a novel and promising approach in targeted therapy, uniting the specificity of antibodies that recognize specific antigens with payloads, all connected by the stable linker. These conjugates combine the best targeted and cytotoxic therapies, offering the killing effect of precisely targeting specific antigens and the potent cell-killing power of small molecule drugs. The targeted approach minimizes the off-target toxicities associated with the payloads and broadens the therapeutic window, enhancing the efficacy and safety profile of cancer treatments. Within precision oncology, ADCs have garnered significant attention as a cutting-edge research area and have been approved to treat a range of malignant tumors. Correspondingly, the issue of resistance to ADCs has gradually come to the fore. Any dysfunction in the steps leading to the ADCs' action within tumor cells can lead to the development of resistance. A deeper understanding of resistance mechanisms may be crucial for developing novel ADCs and exploring combination therapy strategies, which could further enhance the clinical efficacy of ADCs in cancer treatment. This review outlines the brief historical development and mechanism of ADCs and discusses the impact of their key components on the activity of ADCs. Furthermore, it provides a detailed account of the application of ADCs with various target antigens in cancer therapy, the categorization of potential resistance mechanisms, and the current state of combination therapies. Looking forward, breakthroughs in overcoming technical barriers, selecting differentiated target antigens, and enhancing resistance management and combination therapy strategies will broaden the therapeutic indications for ADCs. These progresses are anticipated to advance cancer treatment and yield benefits for patients.

Efficient chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle as "in situ" vaccine integrated tumor ICD and immunoagonist.

INTRODUCTION: Immunotherapy has unprecedentedly opened up a series of neoteric tactics for cancer treatment. As a burgeoning approach, chemo-immunotherapy has innovatively expanded the accomplishments of conventional chemotherapeutic agents for cancer governing. OBJECTIVES: An efficacious chemo-immunotherapy leveraging minimalist electrostatic complex nanoparticle (NP) integrated tumor immunogenic cell death (ICD) and immunoagonist was developed as a watertight "in situ" vaccine for cancer therapy through convenient intratumoral administration with minimized systemic toxicity. METHODS: Chemical-modified pH-sensitive cis-aconityl-doxorubicin (CAD) and immunoadjuvant unmethylated cytosine-phosphate-guanine (CpG) were co-packaged by polycationic polyethylenimine (PEI) though electrostatic-interaction to construct PEI/CpG/CAD NP. By intratumoral injection, this positively charged NP could be detained at tumor site and endocytosed by tumor cells effortlessly. Then, doxorubicin was released through cis-aconityl cleavage induced by endosomal-acidity and further triggered tumor ICD, the moribund tumor cells could release damage-associated molecular patterns (DAMPs) to recruit dendritic cells (DCs). Meanwhile, the entire tumor debris derived into diversified antigens and cooperated with immunostimulatory CpG to excite DC maturation and activated comprehensive antitumor immunity. RESULTS: Prominent tumor suppression was achieved in aggressive mouse melanoma tumor model, which verified the feasibility and effectiveness of this minimalist CAD/CpG-codelivered NP. CONCLUSION: This study has provided a convenient and promising paradigm for potent cancer chemo-immunotherapy.

Eribulin combined with antiangiogenic agents in women with HER2-negative metastatic breast cancer: a retrospective multicenter study.

Background: The relative lack of specifically targeted agents for HER2-negative metastatic breast cancer (MBC) makes the need for new agents or combination therapies to maximize clinical benefit while reducing toxicity critical. Objectives: To retrospectively analyze the efficacy and safety of eribulin combined with antiangiogenic drugs in the treatment of Chinese women with HER2-negative MBC. Methods: A total of 85 consecutive MBC patients with HER2-negative who were treated with eribulin + antiangiogenic agents between October 2020 and April 2023 in four institutions were retrospectively included in this study. Patients received eribulin 1.4 mg/m2 (day 1 and 8) plus bevacizumab 7.5 mg/kg (day 1, 64 patients) or anlotinib 10 mg daily (day 1-14, 16 patients) or apatinib 250 mg daily (5 patients) on a 21-day cycle until progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS), according to Response Evaluation Criteria in Solid tumors (RECIST) 1.1. Secondary end-points included toxicities, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study included 85 HER2-negative MBC patients, with 41 patients (48.2%) in the first to second line group and 44 patients (51.8%) in the greater than or equal to third line group. The median age was 54.0 years. Thirty patients in the first to second line group and 14 patients in the greater than or equal to third line group had triple-negative breast cancer (TNBC). The ORR and DCR were 34.1% (29/85) and 75.3% (64/85). The median PFS (mPFS) of total population was 6.0 months (95% CI: 4.3-7.7), and median OS (mOS) was immature. The mPFS was 7.7 and 4.3 months in the first to second and greater than or equal to third line treatment (p = 0.003), respectively. TNBC patients in first to second line therapy showed a significantly longer PFS (6.5 months versus 2.0 months, p = 0.021) compared to greater than or equal to third line. The incidences of cardiovascular toxicity were 29.4% in grades 1-2 and no grades 3-4. Hematologic toxicity (leukopenia and neutropenia) was the most common grade ⩾3 AEs, and AEs were more common in patients in greater than or equal to third line. Conclusion: The results suggest that eribulin combined with antiangiogenic therapy has a meaningful clinical activity and an acceptable safety profile in HER2-negative MBC.

SERS combined with the difference in bacterial extracellular electron transfer ability to distinguish Shewanella.

Shewanella plays an important role in geochemical cycle, biological corrosion, bioremediation and bioenergy. The development of methods for identifying Shewanella can provide technical support for its rapid screening, in-depth research into its extracellular respiratory mechanism and its application in ecological environment remediation. As a tool for microbial classification, identification and detection, Surface-enhanced Raman scattering (SERS) has high feasibility and application potential. In this work, bio-synthesized silver nanoparticles (AgNPs) were used as SERS substrates to effectively distinguish different types of Shewanella bacteria based on the difference in bacterial extracellular electron transfer (EET) ability. AgNPs were combined with the analyzed bacteria to prepare "Bacteria-AgNPs" SERS samples, which can strongly enhance the Raman signal of the target bacteria and reliably obtain spatial information of different molecular functional groups of each bacteria. Our developed approach can effectively distinguish between non-metal reducing and metal-reducing bacteria, and can further distinguish the three subspecies of Shewanella (Shewanella oneidensis MR-1, Shewanella decolorationis S12, and Shewanella putrefaciens SP200) at the genus and species level. The Raman signal enhancement is presumably caused by the excitation of local surface plasma (LSP) and the enhancement of surrounding electric field. Therefore, our developed method can achieve interspecific and intraspecies discrimination of bacteria. The proposed method can be extended to distinguish other metal-reducing bacteria, and the novel SERS active substrates can be developed for practical applications.

Improved survival in patients with isolated liver metastasis at initial diagnosis with surgery at primary and metastatic sites: A population-based study in patients with breast cancer.

BACKGROUND: The aim of this study was to investigate epidemiological characteristics, risk factors, optimal treatment options, and survival outcomes of breast cancer patients with isolated liver metastasis (BCILM). METHODS: Patients with breast cancer (BC) were selected from Incidence-Surveillance, Epidemiology, and End Results (SEER) Research Plus Data, 17 registries between 2010 and 2019. The Kaplan-Meier method and log-rank test were used to compare survival rates between patients who received or did not receive surgery for the primary and liver metastatic sites. Univariate and multivariate analyses were conducted using Cox regression analysis. RESULTS: This study included 17 743 stage IV BC patients, with 3604 (20.3%) patients experiencing liver metastasis at initial diagnosis. Of 3604 liver metastasis patients, 951 were diagnosed with BCILM. The median survival time of patients with BCILM who underwent surgery at the primary site (52.0 months) or distant sites (85.0 months) was significantly longer than that of patients who did not undergo surgery at the primary site (23.0 months) or distant sites (32.0 months). Univariate analysis indicated that age, race, histological grade, molecular subtype, T stage, N stage, surgery of the primary site, surgery to other regional/distant sites, radiotherapy, and chemotherapy were prognostic factors affecting the overall survival (OS) and cancer-specific survival (CSS) of patients with BCILM (p < 0.05). Multivariate analysis suggested that age, race, molecular subtype, T stage, surgery of the primary site, radiotherapy, and chemotherapy were independent prognostic factors. In the BCILM cohort, HR+ /HER2+ patients exhibited the best OS and CSS, followed by HR- /HER2+ , HR+ /HER2- , and HR- /HER2- patients (p < 0.0001; p < 0.0001). CONCLUSION: Surgery at the primary and metastatic sites was associated with better survival in patients with BCILM. HER2+ patients with BCILM had a significantly better prognosis than HER2- patients.

A phase II study of a doublet metronomic chemotherapy regimen consisting of oral vinorelbine and capecitabine in Chinese women with HER2-negative metastatic breast cancer.

BACKGROUND: This single-arm prospective phase II trial was performed to assess the efficacy and safety of the dual oral metronomic vinorelbine and capecitabine (mNC) regimen in women with HER2-negative metastatic breast cancer (MBC) in China. METHODS: The mNC regimen was administered to the enrolled cases, including oral vinorelbine (VNR) 40 mg three times weekly (on days 1, 3 and 5 every week) and capecitabine (CAP) 500 mg three times a day, until disease progression or intolerable toxicity. The primary endpoint was the 1-year progression-free survival (PFS) rate. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR) and treatment-related adverse events (TRAEs). Stratified factors included treatment lines and hormone receptor (HR) status. RESULTS: Between June 2018 and March 2023, 29 patients were enrolled into the study. The median follow-up time was 25.4 months (range, 2.0-53.8). In the entire group, the 1-year PFS rate was 54.1%. ORR, DCR and CBR were 31.0%, 96.6% and 62.1%, respectively. The mPFS was 12.5 months (range, 1.1-28.1). Subgroup analysis revealed that ORRs were 29.4% and 33.3% in first- and ≥second-line chemotherapy, respectively. ORRs were 29.2% (7/24) and 40.0% (2/5) for HR-positive MBC and metastatic triple-negative breast cancer (mTNBC), respectively. Grade 3/4 TRAEs were neutropenia (10.3%) and nausea/vomiting (6.9%). CONCLUSIONS: The dual oral mNC regimen showed very good safety features and improved compliance without loss of efficacy in both first- and second-line treatments. The regimen also reached an excellent ORR in the mTNBC subgroup.

Botulinum toxin in the treatment of sialorrhea in severe neurological patients with tracheotomy.

OBJECTIVE: To observe the clinical effect of botulinum toxin type A (BTA) injection into the salivary glands of the severe neurological patients with tracheotomy METHODS: Seven patients with severe neurological disorders after tracheotomy and obvious drooling symptoms were enrolled. BTA was injected into bilateral parotid glands and submandibular glands under the guidance of ultrasound. Unstimulated salivary flow rate (uSFR) and Drooling Severity and Frequency Scale (DSFS) were used to evaluate drooling before injection, 1 week, and 4 weeks after injection. We compared the extubation time, time of changing from balloon cannula to metal cannula, hospitalization time and incidence of recurrent pulmonary infection between these patients and other patients accepted conventional curation. RESULTS: (1) The drooling severity scale (DSFS-S), the drooling frequency scale (DSFS-F), the drooling frequency and severity scale total score (DSFS-T) were significantly lower at 4 weeks after BTA injection compared to prior-treatment (p < .001). (2) uSFR of 1 week and 4 weeks were both statistically decreased than the untreated condition (p < .001). (3) Compared with the conventional group, the time of changing from balloon cannula to metal cannula was shortened obviously (p < .05) and incidence of recurrent pulmonary infection was clearly decreased (p < .05) after BTA treatment CONCLUSION: Ultrasound-guided BTA injection into salivary glands can effectively reduce saliva secretion. We also found that the time of changing cannula was shortened obviously and the incidence of recurrent pneumonia infection was reduced. BTA injection of salivary glands to cure drooling could advance to the clinical therapy in severe neurological patients after tracheotomy.

Synergistically enhanced cancer immunotherapy by combining protamine-based nanovaccine with PD-L1 gene silence nanoparticle.

Tumor vaccine has brought a new dawn for cancer immunotherapy, but disillusionary therapeutic outcomes have been achieved due to the inefficient in vivo vaccine delivery. Moreover, tumor cells customarily resort to various wily tricks to circumvent the recognition and sweeping of the immune system, the immune escape effect has badly aggravated the difficulty of cancer management. With respect to the foregoing, in this study, a promising combinational strategy which cooperated nanovaccine with immune escape inhibition was developed for synergistically enhancing the oncotherapy efficiency. On the one hand, natural polycationic macromolecule protamine (PRT) was utilized as the carrier to construct an antigen and adjuvant co-packaged nanovaccine for facilitating the ingestion in antigen-presenting cells, amplifying antigen cross-presentation and optimizing in vivo delivery. On the other hand, PD-L1 silence gene was selected and hitchhiked in a pH-responsive nanoparticle developed in our previous study. The therapeutic gene could be successfully delivered into the tumors to down-regulate PD-L1 expression and cripple tumor immune escape. The combination of nanovaccine with PD-L1 gene silence nanoparticle could synchronously stimulate antitumor immune responses and reduce immune escape, synergistically enhance the therapeutic efficiency. This study will furnish the prospective tactics for the research of cancer immunotherapy.

The trichotomy of HER2 expression confers new insights into the understanding and managing for breast cancer stratified by HER2 status.

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that plays a carcinogenic role in breast cancer (BC) through gene amplification, mutation, or overexpression. Traditional methods of HER2 detection were divided into positive (immunohistochemistry (IHC) 3+/fluorescence in situ hybridization (FISH) amplification) and negative (IHC 2+/FISH-, IHC 1+, IHC 0) according to the dichotomy method. Anti-HER2-targeted therapies, such as trastuzumab and pertuzumab, have significantly improved the prognosis of HER2-positive patients. However, up to 75% to 85% of patients remain HER2-negative. In recent years, with the rapid development of molecular biology, gene detection technology, targeted therapy, and immunotherapy, researchers have actively explored the clinicopathological characteristics, molecular biological characteristics, treatment methods, and HER2 detection methods of HER2-low/zero breast cancer. With the clinical efficacy of new anti-HER2 targeted drugs, accurate classification of breast cancer is very important for the treatment choice. Therefore, the following review summarizes the necessity of developing HER2 detection methods, and the clinicopathological and drug treatment characteristics of patients with HER2-low/zero, to light the dawn of the treatment of breast cancer patients with HER2-low/zero expression.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke.

BACKGROUND AND PURPOSE: The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). METHODS: We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. RESULTS: IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237-0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity. However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. CONCLUSIONS: Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

New era of medical education: asynchronous and synchronous online teaching during and after COVID-19.

COVID-19 struck the world suddenly and unexpectedly. Since traditional education requires face-to-face communication, to avoid further spreading of the virus a majority part of that education has moved online. Our study attempts to compare the differences between online medical education with a unique course design and traditional face-to-face education. We conducted a retrospective analysis of a total of 4,098 medical students between 2019 and 2020, including two groups of students who received online education and classroom education for the same subjects, respectively. Freshmen enrolled in September 2018 received traditional classroom physiology and pharmacology education in the spring semester of 2019. Because of the impact of the COVID-19 pandemic, freshmen who were enrolled in September 2019 received online physiology and pharmacology education in the spring semester of 2020. The final marks of the two groups of students were recorded and compared. Data on students participating in online discussions, learning, homework, and watching instructional videos were also recorded. There was no significant difference in the final academic performance between the two groups [average mark: 55.93 (online education) vs. 56.27 (classroom education), P = 0.488]. Further analysis showed that student participation rates in online discussions, online learning, and online viewing of instructional videos were closely correlated with final grades in online courses (P < 0.01). In conclusion, our results suggest that the pedagogical effects of online education during COVID-19 were promising, and we provide a well-designed medical online course to inspire further improvements in online education.NEW & NOTEWORTHY The COVID-19 pandemic has led to a massive temporary conversion of offline education to online education worldwide. Previous studies have noted that more students believed they had better learning experience in face-to-face learning. However, with our method of online teaching, we still showed a relatively similar performance result compared with offline education.

Caspase-6 is a key regulator of cross-talk signal way in PANoptosis in cancer.

Cysteinyl aspartate specific proteinase (caspase)-6 belongs to the caspase family and plays a vital role in mediating cell death. Under certain conditions, three pathways of programmed cell death (PCD), including apoptosis, necroptosis and pyroptosis (PANoptosis), transform one way into another, with enormous therapeutic potential. Initially, scholars reported that caspase-6 is a caspase executor that mediates apoptosis. With the ceaseless exploration of the PCD types, studies have demonstrated that caspase-6 mediates pyroptosis by regulating gasdermin D and mediates necroptosis by regulating mixed lineage kinase domain-like. By regulating PANoptosis, caspase-6 plays a crucial role in tumorigenesis in humans and mediates anti-tumour immunity. Therefore, a comprehensive understanding of caspase-6 function in cancer via PANoptosis is important for the prevention and therapy of tumours. This article summarized the function of caspase-6 in PANoptosis and its impact on cancer development, providing targets and strategies for tumour treatment.

Leveraging Nanodrug Delivery System for Simultaneously Targeting Tumor Cells and M2 Tumor-Associated Macrophages for Efficient Colon Cancer Therapy.

Tumor-associated macrophages (TAMs) widely exist in the solid tumors, which participate in the entire course of tumor development and execute momentous impacts. Therefore, manipulating TAMs has been identified as an expecting strategy with immense potential for cancer therapy. Herein, a nanodrug delivery system was leveraged for simultaneously targeting tumor cells and M2-type TAMs for efficient colon cancer therapy. The broad-spectrum anticancer chemotherapeutic drug doxorubicin (DOX) was hitchhiked in a mannose-modified bovine serum albumin (MAN-BSA) carrier. The DOX@MAN-BSA nanodrug delivery system was verified to possess feasible physical performances for unhindered systemic circulation and active targeting on colon tumors. DOX@MAN-BSA nanoparticles could be preferentially swallowed by colon tumor cells and M2 TAMs through mannose receptor-mediated endocytosis. Further in vivo antitumor therapy in CT26 colon tumor-bearing mice has achieved remarkable suppression efficacy with satisfactory biosafety. Leveraging the nanodrug delivery system for simultaneously targeting tumor cells and M2 TAMs has contributed a feasible strategy to collaboratively repress the malignant tumor cells and the collusive M2 TAMs for efficient cancer therapy.

Co-loaded lapatinib/PAB by ferritin nanoparticles eliminated ECM-detached cluster cells via modulating EGFR in triple-negative breast cancer.

Cancer stem cell (CSC) cluster of triple-negative breast cancer (TNBC) is suggested to be responsible for therapy resistance, metastatic process and cancer recurrence, yet the sensitivity of CSC clusters of TNBC to ferroptosis remains elusive in a great measure. Current research revealed that epidermal growth factor receptor (EGFR) reinforced CD44-mediated TNBC cell clustering, whether blockade of EGFR has synergistic effects on erastin-induced tumor inhibition of CSC clusters is still poorly understood. Here, we found that fraction of CD24lowCD44high cells and size of tumor spheres clearly decreased following EGFR inhibition in TNBC cells. Inhibition of EGFR promoted expression of LC3B-II via YAP/mTOR signaling pathway, indicating that EGFR-mediated autophagy which contributed to ferroptosis. In order to further verify the protective effects of EGFR on ferroptosis induced by small molecules in TNBC cells, pseudolaric acid B (PAB) which led to ferroptosis of malignant cells was selected. In our experiment, lapatinib and PAB cotreatment inhibited TNBC cells viability and restrained formation of tumor spheres, accompanied with a high level of intracellular ROS. To target delivery lapatinib and PAB to TNBC cells, lapatinib/PAB@Ferritin (L/P@Ferritin) nanoparticles were prepared; results of in vitro and in vivo showed a higher tumor suppression efficiency of L/P@Ferritin, highlighting that it might provide a new perspective for treatment of CSC clusters of TNBC.

Buffet-style Cu(II) for enhance disulfiram-based cancer therapy.

Studies have shown that disulfiram (DSF) can combine with Cu2+ to form bis(N, N-diethyldithiocarbamate) copper(II) complex (CuET) as antitumor drugs. However, there is insufficient endogenous Cu2+ dose to eradicate cancer cells selectively. Inspired by the buffet, we use Cu2+ doped hollow zeolitic imidazolate framework nanoparticles (HZIFCu) as the carrier and equipped with DSF and indocyanine green (ICG) and targeted by folic acid (FA) (D&I@HZIFCu-FA) to enhance DSF-based cancer therapy. D&I@HZIFCu-FA could effectively supply Cu2+ by a buffet-style, assisting the "DSF-to-CuET" transformation in the tumor. Additionally, self-supply Cu2+ could convert H2O2 into ·OH by triggering a Fenton-like reaction for chemo-dynamic therapy, and ICG achieves photothermal therapy for tumors under laser irradiation. This work provides a buffet-style for Cu2+ to make DSF a strong candidate for cancer treatment by combining chemotherapy, chemo-dynamic therapy, and photothermal therapy and inspires more research about its applications in tumor therapy.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a major life-threatening consequence of cardiac myxoma (CM) and leads to a poor prognosis. Although intravenous thrombolysis (IVT) is the first-line treatment for AIS, its efficacy and safety in CM-AIS have not been established. Currently, there are only limited data from case reports. Our study aimed to investigate the clinical characteristics of CM-AIS and evaluate the safety and efficacy of IVT for CM-AIS patients. Methods: Fourteen CM-AIS patients who received IVT between January 2016 and December 2021 were identified from our multicenter stroke registry databases. Clinical, neuroimaging and outcome data were analyzed. We then performed a pooled analysis of the published literature from inception to December 2021. Results: Of the 14 CM-AIS patients, nine were treated with IVT alone, and five were treated with bridging therapy (BT). The median age was 51.5 years, and 57.1% were female. The median onset-to-needle time was 160 min. The median National Institute of Health Stroke Score (NIHSS) decreased from 15.5 at presentation to 13 24 h after IVT. Very early neurological improvement (VENI) was observed in one patient. Hemorrhagic transformation (HT) was observed in five (35.7%) patients, and only one patient was symptomatic (7.1%). Three-month favorable outcomes were achieved in six patients (66.7%) who underwent IVT alone and three patients (60%) who received BT, which resulted in a total proportion of favorable outcomes of 64.3%. None of the patients died at 3 months follow-up. Forty-seven cases (15 BT patients) were included for the pooled analysis. The median NIHSS score was 16.5, and VENI was observed in 10 (21.3%) patients. HT was detected in 11 patients (23.4%), and four (8.5%) patients were symptomatic. Favorable outcomes at 3 months were achieved in 61.7% of patients, 56.3% of patients who underwent IVT alone, and 73.3% of patients who received BT. The 3-month mortality rate was 4.3%. Conclusions: IVT is a potentially safe and efficient treatment for CM-AIS patients. Further studies with larger sample sizes are required to provide more evidence on the safety and efficacy of IVT and BT in CM-AIS patients.

Mechanical Thrombectomy for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a common and life-threatening complication of patients with cardiac myxoma (CM). The role of the mechanical thrombectomy (MT) technique in CM-AIS patients remains unclear, and no guidelines exist for this population. Therefore, we conducted a case series study of MT in CM-AIS patients to investigate its safety and efficacy via a pooled analysis of published literature. Methods: Eleven CM-AIS patients who underwent MT between 2016 and 2021 were screened from multicenter stroke databases. Clinical, procedural, and outcome data were obtained from medical records. A systematic review was conducted to identify additional cases from published studies by searching PubMed and China National Knowledge Infrastructure databases. We then performed a pooled analysis of the published cases. Results: In the case series study, most patients were male (81.8%), with a median age of 51 years. All patients had CM located in the left atrium. The rate of successful reperfusion using the first-line thrombectomy technique was 100% with stent retriever (SR) and 66.7% with direct aspiration (DA), which resulted in overall successful reperfusion in 94.1% of all occlusions. The retrieved emboli of the five patients who underwent histopathology examination were identified as myxoma components. Hemorrhagic transformation was observed in five (45.5%) patients, of whom one was symptomatic (9.1%). Three-month favorable functional outcomes were achieved in five (45.5%) patients with a 3-month mortality rate of 18.2%. For the literature review, 35 cases with 51 target vessel occlusions were identified and included in the pooled analysis. The rate of successful reperfusion following first-line thrombectomy did not differ between SR (30 patients, 90.9%) and DA (10 patients, 83.3%). The overall successful reperfusion rate was 91.8% of all occlusions. Three-month favorable functional outcomes were achieved in 21 (60.0%) patients, and the mortality rate was 8.6%. Conclusions: Our findings suggest that MT is not only an effective technique but also a safe option for CM-AIS patients with large vessel occlusion. MT has several advantages for this population, which include a high recanalization rate, low bleeding risk, and the ability to evaluate the source of emboli and the etiology of stroke.

Cooperating minimalist nanovaccine with PD-1 blockade for effective and feasible cancer immunotherapy.

Introduction: Tumor vaccine has been a research boom for cancer immunotherapy, while its therapeutic outcome is severely depressed by the vulnerable in vivo delivery efficiency. Moreover, tumor immune escape is also another intractable issue, which has badly whittled down the therapeutic efficiency. Objectives: Our study aims to solve the above dilemmas by cooperating minimalist nanovaccine with PD-1 blockade for effective and feasible cancer immunotherapy. Methods: The minimalist antigen and adjuvant co-delivery nanovaccine was developed by employing natural polycationic protamine (PRT) to carry the electronegative ovalbumin (OVA) antigen and unmethylated Cytosine-phosphorothioate-Guanine (CpG) adjuvant via convenient chemical bench-free "green" preparation without chemical-synthesis and no organic solvent was required, which could preserve the immunological activities of the antigens and adjuvants. On that basis, PD-1 antibody (aPD-1) was utilized to block the tumor immune escape and cooperate with the nanovaccine by maintaining the tumoricidal-activity of the vaccine-induced T cells. Results: Benefited from the polycationic PRT, the facile PRT/CpG/OVA nanovaccine displayed satisfactory delivery performance, involving enhanced cellular uptake in dendritic cells (DCs), realizable endosomal escape and promoted stimulation for DCs' maturation. These features would be helpful for the antitumor immunotherapeutic efficiency of the nanovaccine. Furthermore, the cooperation of the nanovaccine with aPD-1 synergistically improved the immunotherapy outcome, profiting by the cooperation of the "T cell induction" competency of the nanovaccine and the "T cell maintenance" function of the aPD-1. Conclusion: This study will provide new concepts for the design and construction of facile nanovaccines, and contribute valuable scientific basis for cancer immunotherapy.

Selective thermotherapy of tumor by self-regulating photothermal conversion system.

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.