An Integrated Clinical and Computerized Tomography-Based Radiomic Feature Model to Separate Benign from Malignant Pleural Effusion.

INTRODUCTION: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. METHODS: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. CONCLUSION: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.

Impact of Serum Cystatin C Level on Long-Term Cognitive Impairment After Acute Ischemic Stroke and Transient Ischemic Attack.

Objective: Cognitive impairment after stroke/transient ischemic attack (TIA) has a high prevalence. Cystatin C (CysC) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer's disease. We aimed to explore the possible correlations of serum CysC level with cognitive impairment in patients who had mild ischemic stroke and TIA after 1 year. Methods: We measured serum CysC level in 1025 participants with a minor ischemic stroke/TIA from enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were divided into four groups according to quartiles of baseline CysC levels. Patients' cognitive functions were assessed by Montreal Cognitive Assessment (MoCA)-Beijing at day 14 and at 1 year. Multiple logistic regression models were performed to evaluate the relationship between CysC and post-stroke cognitive impairment (PSCI) at 1-year follow-up. Results: Cognitive impairment was defined as MoCA-Beijing ≤22. Most patients were in 60s (61.52±10.97 years old) with a median (interquartile range) National Institute of Health Stroke Scale(NIHSS) score of 3.00 (4.00) and greater than primary school level of education, and 743 participants (72.49%) were male. Among the 1025 participants, 331 participants (32.29%) patients suffered PSCI at 1-year follow-up. A U-shaped association was observed between CysC and 1-year PSCI [quartile (Q)1 vs Q3: adjusted odds ratio (aOR) 2.69, 95% CI 1.67-4.34, p < 0.0001; Q2 vs Q3: aOR 1.63, 95% CI 1.03-2.57, p = 0.0354; Q4 vs Q3: aOR 1.83, 95% CI 1.16-2.87, p = 0.009]. Moreover, the U-shaped trends were also found between CysC level and the subscores of attention, recall, abstraction and language in MoCA. Conclusion: CysC showed a U-shaped correlation with 1-year overall cognitive function. It is probable that measurement of the serum CysC level would aid in the early diagnosis of PSCI.

Matrix stiffness, endothelial dysfunction and atherosclerosis.

Atherosclerosis (AS) is the leading cause of the human cardiovascular diseases (CVDs). Endothelial dysfunction promotes the monocytes infiltration and inflammation that participate fundamentally in atherogenesis. Endothelial cells (EC) have been recognized as mechanosensitive cells and have different responses to distinct mechanical stimuli. Emerging evidence shows matrix stiffness-mediated EC dysfunction plays a vital role in vascular disease, but the underlying mechanisms are not yet completely understood. This article aims to summarize the effect of matrix stiffness on the pro-atherosclerotic characteristics of EC including morphology, rigidity, biological behavior and function as well as the related mechanical signal. The review also discusses and compares the contribution of matrix stiffness-mediated phagocytosis of macrophages and EC to AS progression. These advances in our understanding of the relationship between matrix stiffness and EC dysfunction open the avenues to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.

Development of magnetic poly(L-lactic Acid) nanofibrous microspheres for transporting and delivering targeted cells.

To avoid infection and other risks caused by large open-surgery incisions using scaffold transplants, it is very important to study injectable microcarrier-loaded cells for targeted therapy and tissue regeneration. In this study, on the one hand, to simulate the hierarchical structure of the extracellular matrix and carry cells, poly(L-lactic acid) (PLLA) nanofibrous microspheres (large microspheres) were initially fabricated as cell carriers. On the other hand, to precisely deliver cells through a magnetic field and promote stem cell differentiation, drug-loaded mesoporous Fe3O4@SiO2 microspheres (small microspheres) were prepared and coated on the surface PLLA nanofibrous microspheres. The coating conditions were systematically studied and optimized. The results showed that planetary-satellite-like cell carriers were successfully prepared and the carriers were capable of freely translocating under the influence of a magnetic field. It has been demonstrated in vitro experiments that the carriers are biocompatible and are capable of acting as drug carriers. Specifically, they were able to load and release cells in response to magnetic fields. In vivo experiments indicated that the carriers could successfully load and release GFP-labelled cells in nude mice. The study presented in this paper provides a versatile and promising platform for the cell-based therapy in tissue engineering and regenerative medicine.

Stainless Steel Screen Modified with Renatured Xerogel for Efficient and Highly Stable Oil/Water Separation via Gravity.

The application of hydrogel coatings to surface-modified metallic materials has gained considerable attention in engineering practice such as water-oil separation. However, the low coating adhesion and poor coating stability restrict its application. In this study, to obtain special wettability and durable filter materials, polyacrylamide (PAM)/sodium alginate (SA) xerogel particles were first prepared and adhered to a stainless steel screen by using an epoxy resin as a linker. Subsequently, the xerogel particles of the screen rehydrates in water to form a PAM-SA double-network hydrogel. The results show that the screen modified by PAM-SA xerogel of 20-30 µm particle size and a linker concentration of 0.1 g/mL resulted in a chimeric structure and subsequently transformed a uniform double-network hydrogel coating in water. According to the experimental results, the rough hydrogel coating exhibits superhydrophilicity and superoleophobicity under water; in particular, it has excellent wear resistance as well as physical and chemical stability. Under gravity-driven action, the PAM-SA-modified screen demonstrates high separation efficiency values of up to 99% in separating a wide range of oil/water mixtures and maintaining a water flux of (2-6) × 104 L·m-2·h-1. There was no significant reduction in efficiency of separation and water flux after 10 cycles, indicating that the PAM-SA-modified screen is capable of offering outstanding separation performance and durability. Moreover, the hydrogel-modified screen demonstrated corrosion and swelling resistance in some extreme environments, paving a way for practical applications in water treatment. The novel hydrogel-coating-modified screen with ease of preparation holds great promise for oil/water separation and other engineering applications.

Targeting Microglial Metabolic Rewiring Synergizes with Immune-Checkpoint Blockade Therapy for Glioblastoma.

Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single-cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2+/-) or CX3CR1+ myeloid cell-specific Nr4a2 (Nr4a2fl/flCx3cr1Cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacologic NR4A2 inhibition attenuated the protumorigenic TIME, and targeting the NR4A2 or SQLE enhanced the therapeutic efficacy of immune-checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer. SIGNIFICANCE: Metabolic reprogramming of microglia in GBM informs synergistic vulnerabilities for immune-checkpoint blockade therapy in this immunologically cold brain tumor. This article is highlighted in the In This Issue feature, p. 799.

Bio-inspired Oxidative Stress Amplifier for Suppressing Cancer Metastasis and Imaging-Guided Combination Therapy.

Antioxidant-defense systems of tumor cells protect them from oxidative damage and is strongly associated with tumor metastasis. In this work, a mussel-inspired multifunctional nanomedicine (ZS-MB@P) has been designed for inhibiting tumor growth and metastasis through amplified oxidative stress and photothermal/magnetothermal/photodynamic triple-combination therapy. This nanomedicine was fabricated via loading a silica shell on the magnetic nano-octahedrons [zinc-doped magnetic Fe3O4 nano-octahedrons] by encapsulating photosensitizer methylene blue (MB) and subsequently coating polydopamine (PDA) shells as "gatekeeper." The nanomedicine could realize photothermal therapy, photodynamic therapy, and magnetic hyperthermia after treatment with near-infrared (NIR) irradiation and applied magnetic field. Under pH and NIR stimulation, controlled amount of MB was released to produced exogenous reactive oxygen species. Noteworthy, PDA can amplify intracellular oxidative stress by depleting glutathione, thus inhibiting breast cancer metastasis effectively since oxidative stress is an important barrier to tumor metastasis. The outstanding ability to suppress tumor growth and metastasis was comprehensively assessed and validated both in vitro and in vivo. Moreover, the nanomedicine showed outstanding T2 magnetic resonance imaging for tracking the treatment process. Taken together, this work offers an innovative approach in the synergistic treatment of recalcitrant breast cancer.

Mesoporous Silica Nanoparticles-Based Nanoplatforms: Basic Construction, Current State, and Emerging Applications in Anticancer Therapeutics.

In recent years, researchers are developing novel nanoparticles for diagnostic applications using imaging techniques and for therapeutic purposes through drug delivery techniques. The unique physical and chemical properties of mesoporous silica nanoparticles (MSNs) make it possible to integrate a variety of commonly used therapeutic and imaging agents to construct a multimodal synergistic anticancer drug delivery system. Herein, recent advances in MSNs synthesis for drug delivery and smart response applications are reviewed. First, synthetic strategies for the fabrication of ordered MSNs, hollow MSNs, core-shell structured MSNs, dendritic MSNs, and biodegradable MSNs are outlined. Then, the recent research progress in designing functional MSN materials with various controlled release mechanisms in anticancer therapy is discussed, and new properties are introduced to suggest the latest design requirements as drug delivery materials. The review also highlights significant achievements in bioimaging using MSNs and their multifunctional counterparts as delivery vehicles. Finally, personal views on key directions for future work in this area are presented.

Efficacy and safety of different Janus kinase inhibitors combined with methotrexate for the treatment of rheumatoid arthritis: a single-center randomized trial

Abstract Objective To compare the efficacy and safety between baricitinib (BARI) and tofacitinib (TOFA) for the treatment of the rheumatoid arthritis (RA) patients receiving methotrexate (MTX) in clinical practice. Methods This retrospective study recruited 179 RA patients treated with BARI (2-4 mg/d) or TOFA (10 mg/d) at The First Affiliated Hospital of Guangxi Medical University from September 2019 to January 2022. The rate of low disease activity (LDA) was used as the primary end point. Secondary end points included the Disease Activity Scale-28 (DAS-28)-C-reactive protein (CRP); the rate of DAS28-CRP remission; visual analogue scale (VAS) for pain, swollen joint, and tender joint counts; and adverse events at the 6-month follow-up. Several factors affecting LDA achievement were also analyzed. Results Seventy-four patients were treated with BARI and 105 were treated with TOFA, including 83.24% females, with a median (IQR) age of 56.0 (53.0-56.0) years old and disease duration of 12.0 (6.0-12.0) months. There was no difference of the rate of LDA between the BARI and TOFA treatment groups. All disease indices in the two groups were significantly improved, including a significantly lower VAS in the BARI group (P < 0.05), reflecting the drug efficacy after 1 and 6 months of treatment. The incidence of adverse reactions was similar in these two groups. Conclusion The treatment efficacy and safety of BARI and TOFA in the RA patients were similar, but BARI was more effective in pain relief than TOFA. An older baseline age was more likely to achieve LDA in the BARI group, while a low baseline erythrocyte sedimentation rate (ESR) was more likely to achieve LDA in the TOFA group.

[Clinical Features and Surgical Outcomes of 15 Cases of Intracranial Alveolar Echinococcosis]. / 15ä¾‹é¢ å† æ³¡åž‹æ£˜çƒèš´ç— çš„ä¸´åºŠç‰¹ç‚¹åŠæ‰‹æœ¯ç–—æ•ˆåˆ†æž.

Objective: To investigate the surgical treatment strategy of intracranial alveolar echinococcosis (AE) and the clinical outcomes. Methods: The clinical and follow-up data of 15 intracranial AE patients who underwent surgical treatment in the Departments of Neurosurgery of Sichuan Provincial People's Hospital (SPPH) and People's Hospital of Aba Tibetan and Qiang Autonomous Prefecture (a branch hospital of SPPH) between March 2017 and January 2021 were retrospectively analyzed. Full follow-up data were available for each of the 15 cases. The clinical and imaging characteristics, general surgical information, and surgical outcomes were analyzed. Results: In the 15 patients, there were a total of 50 intracranial lesions, with an average of (3.3±3.1)/case. Four cases had solitary intracranial lesions, while 11 cases had multiple lesions, with the number of intracranial lesions per case ranging from 2 to 13. All patients with solitary intracranial lesions received total resection. In 6 patients with multiple intracranial lesions, only the largest lesion was surgically removed, and in 5 patients, 2 to 3 adjacent lesions were surgically removed. All but one patient had extracranial lesions in their liver, lungs, kidneys, adrenal glands, and thoracic vertebrae. The patients were followed up for 12 to 58 months after surgery, with the mean follow-up time being (28.1±13.4) months. Among the 15 cases, 13 showed stable intracranial condition during postoperative follow-up. Intracranial lesions recurred in 2 patients who had deep lesions accompanied by dissemination to the subarachnoid space. Two patients died during follow-up. Conclusion: Microsurgical treatment of intracranial AE is effective, but total surgical resection is difficult to accomplish when patients have echinococcosis lesions located at a depth, especially when the lesions are spreading to the subarachnoid space. The prognosis of patients is closely associated with the extent of lesion invasion and the control of systemic hydatid lesions, especially those in the liver.

Shear stress enhances anoikis resistance of cancer cells through ROS and NO suppressed degeneration of Caveolin-1.

Circulating tumor cells (CTCs) acquire enhanced anti-anoikis abilities after experiencing flow shear stress in the circulatory system. Our previous study demonstrated that low shear stress (LSS) promotes anoikis resistance of human breast carcinoma cells via caveolin-1 (Cav-1)-dependent extrinsic and intrinsic apoptotic pathways. However, the underlying mechanism how LSS enhanced Cav-1 expression in suspended cancer cells remains unclear. Herein, we found that LSS induced redox signaling was involved in the regulation of Cav-1 level and anoikis resistance in suspension cultured cancer cells. Exposure of human breast carcinoma MDA-MB-231 cells to LSS (2 dyn/cm2) markedly induced ROS and •NO generation, which promoted the cell viability and reduced the cancer cell apoptosis. Furthermore, ROS and •NO scavenging inhibited the upregulation of Cav-1 by interfering ubiquitination, and suppressed the anoikis resistance of suspended tumor cells. These findings provide new insight into the mechanism by which LSS-stimulated ROS and •NO generation increases Cav-1 stabilization in suspended cancer cells through inhibition of ubiquitination and proteasomal degradation, which could be a potential target for therapy of metastatic tumors.

Caveolin-1 signaling-driven mitochondrial fission and cytoskeleton remodeling promotes breast cancer migration.

Mitochondria are highly dynamic organelles that constantly divide and fuse to maintain their proper structure and function. Cancer cells are often accompanied by an imbalance of mitochondrial fusion and fission, cancer progression is greatly affected by this imbalance. Here, we found that high-metastatic breast cancer MDA-MB-231 cells possess higher caveolin-1 (Cav-1) expression compared with low-metastatic breast cancer MCF-7 cells or normal breast epithelial MCF-10A cells. Downregulation of Cav-1 decreases the migratory and invasive abilities of MDA-MB-231 cells. Our results further demonstrated that downregulation of Cav-1 facilitated DRP1 and MFN2 to translocate to mitochondria, increasing the inhibitory phosphorylation level of DRP1 at Ser637 by protein kinase A (PKA), resulting in mitochondria elongation. We also showed that downregulation of Cav-1 significantly reduced the Rac1 activity by affecting intracellular reactive oxygen species (ROS) generation, which then inhibited F-actin formation. Based on these findings, we proposed that Cav-1 mediated mitochondrial fission-affected intracellular ROS generation and activated Rho GTPases, leading to F-actin-dependent formation of lamellipodia and promotion of breast cancer motility.

Vascular Risk Factors, Imaging, and Outcomes in Transient Ischemic Attack/Ischemic Stroke Patients with Neuroimaging Evidence of Probable/Possible Cerebral Amyloid Angiopathy.

BACKGROUND: In TIA/ischemic stroke patients, the clinical significance of lobar microbleeds potentially indicating cerebral amyloid angiopathy (CAA) is unknown. We assessed vascular risk factors and outcomes, including cognition, in TIA/ischemic stroke patients with neuroimaging evidence of probable/possible CAA. METHODS: This prospective cohort was conducted from August 2015 and January 2018 at 40 centers. 2625 participants were collected. Eligible participants were aged at least 55 years. Montreal Cognitive Assessment (MoCA) score is less than or equal to 26. A total of 1620 patients were included. 1604 (99.0%) and 1582 (97.7%) participants are followed up at 3 and 12 months. The primary outcomes were death or disability (mRS score, 3-6) and Montreal Cognitive Assessment (MoCA) at 3 months and 12 months. Demographic and vascular risk factors were measured at baseline (smoking, alcohol, diabetes, atrial fibrillation, hypertension, hypercholesterolemia, coronary artery disease, ischemic stroke, and transient ischemic attack). Blood samples were collected within 24 hours of admission. MRI was recommended for all patients. MoCA score was evaluated at baseline and follow-up. RESULTS: In total, 291/1620 patients with ischemic stroke/TIA (32.7% female and mean age, 67.8 years) had neuroimaging evidence of probable/possible CAA. Higher age, history of hypertension, atrial fibrillation, ischemic stroke, alcohol, and high glucose at the admission were more common in the patients. Mean MoCA changed from 21.4 at 3 months (SD 5.2) to 22.3 at 12 months (SD 4.7), difference 0.3 (SD 3.8). At the 3-month and 12-month follow-up, there were significant differences in age, education level, and sex among different cognitive groups. Higher age, lower education (less than high school), and female sex were the predictors of changing in MoCA score from 3 months to 12 months. Moreover, age (more than 66 years) and education (less than high school) are strongly associated with MoCA at 3- and 12-month follow-up. 30 of 286 (10.5%) and 37 of 281 (13.2%) patients had poor outcome of death or disability (modified Rankin Scale score, 3-6) at follow-up 3 and 12 months. Cortical superficial siderosis (cSS) was associated with higher mRS at follow-up. cSS status, cSS count 1-2, cSS strictly lobar, and strictly deep might be the risks of outcomes in adjusted analyses. CONCLUSION: This study suggested that an increasing number of vascular risk factors and imaging markers were significantly associated with outcomes of TIA/ischemic stroke patients with CAA pattern. Male, young patients with high education should get better cognitive recovery.

Impact of Sleep Duration on Depression and Anxiety After Acute Ischemic Stroke.

Background: Abnormal sleep duration predicts depression and anxiety. We seek to evaluate the impact of sleep duration before stroke on the occurrence of depression and anxiety at 3 months after acute ischemic stroke (AIS). Methods: Nationally representative samples from the Third China National Stroke Registry were used to examine cognition and sleep impairment after AIS (CNSR-III-ICONS). Based on baseline sleep duration before onset of stroke as measured by using the Pittsburgh Sleep Quality Index (PSQI), 1,446 patients were divided into four groups: >7, 6-7, 5-6, and <5 h of sleep. Patients were followed up with the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) for 3 months. Poststroke anxiety (PSA) was defined as GAD-7 of ≥5 and poststroke depression (PSD) as PHQ-9 of ≥5. The association of sleep duration with PSA and PSD was evaluated using multivariable logistic regression. Results: The incidences of PSA and PSD were 11.2 and 17.6% at 3 months, respectively. Compared to a sleep duration of >7 h, 5-6 h, and <5 h of sleep were identified as risk factors of PSA [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.24-3.07; P < 0.01 and OR, 3.41; 95% CI, 1.94-6.04; P < 0.01) and PSD (OR, 1.47; 95% CI, 1.00-2.17; P = 0.04 and OR, 3.05; 95% CI, 1.85-5.02; P < 0.01), while 6-7 h of sleep was associated with neither PSA (OR, 1.09; 95% CI, 0.71-1.67; P = 0.68) nor PSD (OR, 0.92; 95% CI, 0.64-1.30; P = 0.64). In interaction analysis, the impact of sleep duration on PSA and PSD was not affected by gender (P = 0.68 and P = 0.29, respectively). Conclusions: Sleep duration of shorter than 6 h was predictive of anxiety and depression after ischemic stroke.

Injectable open-porous PLGA microspheres as cell carriers for cartilage regeneration.

Minimally invasive treatment via injectable delivery of cells has drawn extensive attention for tissue regeneration because it reduces the need for substantial open surgery and fits tissue defects with complex shapes, making it a suitable option for repairing articular cartilage defects. This work presents an alkaline treatment method to fabricate open-porous poly (lactic-co-glycolic acid) microspheres (OPMs) as bone marrow stromal cells (BMSCs) carriers for cartilage regeneration. OPMs have better biodegradation property and the extended pores can provide easier access for cells to the internal space. The BMSCs cultured with OPMs can display enhanced cell proliferation, up-regulated expression of cartilage-related mRNAs and proteins, and improved cartilage regeneration in vitro and in vivo. These results highlight the advantage and potential of using OPMs fabricated via simple alkaline treatment as injectable stem cell carriers for cartilage regeneration through minimally invasive procedures.

Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish.

Increasing evidence has demonstrated that cadmium accumulation in the blood increases the risk of neurological diseases. However, how cadmium breaks through the blood-brain barrier (BBB) and is transferred from the blood circulation into the central nervous system is still unclear. In this study, we examined the toxic effect of cadmium chloride (CdCl2) on the development and function of BBB in zebrafish. CdCl2 exposure induced cerebral hemorrhage, increased BBB permeability and promoted abnormal vascular formation by promoting VEGF production in zebrafish brain. Furthermore, in vivo and in vitro experiments showed that CdCl2 altered cell-cell junctional morphology by disrupting the proper localization of VE-cadherin and ZO-1. The potential mechanism involved in the inhibition of protein tyrosine phosphatase (PTPase) mediated by cadmium-induced ROS was confirmed with diphenylene iodonium (DPI), a ROS production inhibitor. Together, these data indicate that BBB is a critical target of cadmium toxicity and provide in vivo etiological evidence of cadmium-induced neurovascular disease in a zebrafish BBB model.

Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications.

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy. Methods: Based on macrophage "homing" into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined in vitro. Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined. Results: The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells in vitro. In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions in vivo. After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration. Conclusion: These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.

Relationship between homocysteine levels and post-stroke cognitive impairment in female and male population: from a prospective multicenter study.

BACKGROUND AND OBJECTIVES: To investigate the relationship between homocysteine levels and post-stroke cognitive impairment (PSCI) in Chinese female and male populations with minor acute ischemic stroke or transient ischemic attack. MATERIALS AND METHODS: A total of 1070 participants with clinically confirmed acute minor ischemic stroke or transient ischemic attack and baseline homocysteine information from a nationwide multicenter prospective registry study in China were included in this study. Of these, 919 patients had cognitive assessments at 3-month follow-ups and 584 participants had cognitive assessments at 12-month follow-ups. The incidence of PSCI was defined as a Montreal Cognitive Assessment score ≤22. The differences in homocysteine levels and the incidence of PSCI were compared between female and male populations. Relationships between homocysteine levels and the incidence of PSCI in female and male populations were analyzed using multiple logistic regression, respectively. RESULTS: Females had lower baseline homocysteine levels than males. Compared to males, females had lower education levels, lower rates of smoking and alcohol intake, and higher rates of diabetes and hypertension. No relationship was observed between elevated homocysteine level and 3-month PSCI incidence in either females or males. After adjusting the confounders, elevated baseline homocysteine significantly increased the 12-month PSCI risk (odds ratio 3.28, 95% confidence interval 1.47-7.34, P = 0.004) in females, but not in males (odds ratio 0.86, 95% confidence interval 0.49-1.49, P = 0.586). CONCLUSION: Elevated homocysteine levels increased the 12-month PSCI risk in females, but not in males with minor acute ischemic stroke or transient ischemic attack.

Screening for cognitive impairment with the montreal cognitive assessment at six months after stroke and transient ischemic attack.

OBJECTIVE: Cognitive impairment usually occurs in the acute phase after stroke, but most stroke survivors experience some form of long-term cognitive deficit. The aim of this study was to establish the cutoff point of the Montreal Cognitive Assessment (MoCA-Beijing) in screening for cognitive impairment (CI) at 6 months of ischemic stroke or transient ischemic attack (TIA). METHODS: A total of 301 stroke patients and 15 TIA patients were recruited. Patients were assessed at six months by the MoCA-Beijing and a formal neuropsychological battery. The 1.5 SD below the level of the norm on several tests indicated cognitive impairment (CI). RESULTS: Most stroke and TIA patients were in their 60s (61.23 ± 10.60 years old). The optimal cutoff point for MoCA-Beijing in discriminating patients with CI from those with no cognitive impairment (NCI) was 24/25 (sensitivity 63.28%, specificity 71.22%, PPV = 73.68%, NPV = 60.37%, classification accuracy = 66.72%). The predominant cognitive deficits were visuospatial ability (84.85%), and then attention/executive function (79.27%). CONCLUSION: The MoCA-Beijing cutoff score for differentiating CI from NCI after stroke and TIA at six months was at 24/25, and it is important for routine clinical practice.

Fabrication of protease XIV-loaded microspheres for cell spreading in silk fibroin hydrogels.

Due to their excellent mechanical strength and biocompatibility, silk fibroin(SF) hydrogels can serve as ideal scaffolds. However, their slow rate of natural degradation limits the space available for cell proliferation, which hinders their application. In this study, litchi-like calcium carbonate@hydroxyapatite (CaCO3@HA) porous microspheres loaded with proteases from Streptomyces griseus (XIV) were used as drug carriers to regulate the biodegradation rate of SF hydrogels. The results showed that litchi-like CaCO3@HA microspheres with different phase compositions could be prepared by changing the hydrothermal reaction time. The CaCO3@HA microspheres controlled the release of Ca ions, which was beneficial for the osteogenic differentiation of mesenchymal stem cells (MSCs). The adsorption and release of protease XIV from the CaCO3@HA microcarriers indicated that the loading and release amount can be controlled with the initial drug concentration. The weight loss test and SEM observation showed that the degradation of the fibroin hydrogel could be controlled by altering the amount of protease XIV-loaded CaCO3@HA microspheres. A three-dimensional (3D) cell encapsulation experiment proved that incorporation of the SF hydrogel with protease XIV-loaded microspheres promoted cell dispersal and spreading, suggesting that the controlled release of protease XIV can regulate hydrogel degradation. SF hydrogels incorporated with protease XIV-loaded microspheres are suitable for cell growth and proliferation and are expected to serve as excellent bone tissue engineering scaffolds.