Blood cadmium level as a risk factor for chronic pain: NHANES database 1999-2004.

Objective: The escalating prevalence of chronic pain poses a substantial socio-economic burden. Chronic pain primarily stems from musculoskeletal and nervous system impairments. Given cadmium's known toxicity to these systems, our study sought to investigate the correlation between blood cadmium levels and chronic pain. Methods: The cross-sectional study was conducted from the National Health and Nutrition Examination Survey (NHANES, 1999-2004), and comprised US adults who participated in a chronic pain interview. We employed logistic regression models and smooth curve fitting to elucidate the relationship between blood cadmium levels and chronic pain. Results: Our findings revealed a linear association between blood cadmium levels and chronic pain. Compared to the lower blood cadmium tertile 1 (<0.3 ug/dL), the adjusted odds ratios (ORs) for tertile 2 (0.3-0.4 ug/dL), and tertile 3 (≥0.5 ug/dL), were 1.11 (0.96-1.29) and 1.2 (1.03-1.39), respectively. Sensitivity analyses corroborated these results. Conclusion: Elevated levels of blood cadmium are associated with a heightened risk of chronic pain among adults in the United States. Mitigating cadmium exposure could potentially decrease the risk of chronic pain, thereby enhancing strategies for chronic pain prevention and management.

Association between HDL-C and chronic pain: data from the NHANES database 2003-2004.

Objective: High-density lipoprotein cholesterol (HDL-C) has been reported to be associated with pain symptoms of various diseases, and its anti-inflammatory and antioxidant mediation is related to the pathogenesis of chronic pain. This study aims to evaluate the relationship between HDL-C levels and chronic pain in American adults. Methods: This cross-sectional study used data from American adults aged 20 and above during the 2003-2004 National Health and Nutrition Examination Survey (NHANES) cycle. Participants were divided into 4 groups based on HDL-C quartiles. We used chi-square tests and Student's t-tests or Mann-Whitney U tests to analyze categorical variables and continuous variables to compare differences between groups. Multivariate logistic regression analysis was used to study the association between HDL-C levels and the risk of chronic pain. Likelihood ratio tests were used to assess interactions between subgroups, and sensitivity analyses were conducted. Results: Our final analysis included 4,688 participants, of which 733 (16.4%) had chronic pain. In the multivariate logistic regression model adjusted for covariates, there was a negative correlation between HDL-C levels and chronic pain. Specifically, for every 20 unit increase in HDL-C, the risk of chronic pain decreased by 26%. Compared with the lowest HDL-C quartile (< 43 mg/dL), the highest HDL-C quartile (≥ 64 mg/dL) was associated with a 24% reduction in the risk of chronic pain. No interaction factors affecting the relationship between HDL-C and chronic pain were found in the subgroup analysis. Conclusion: This study demonstrates a negative association between HDL-C levels and chronic pain in US adults, providing insights into the pathogenesis of chronic pain and potential improvements in chronic pain management strategies.

Integrated machine learning survival framework develops a prognostic model based on inter-crosstalk definition of mitochondrial function and cell death patterns in a large multicenter cohort for lower-grade glioma.

BACKGROUND: Lower-grade glioma (LGG) is a highly heterogeneous disease that presents challenges in accurately predicting patient prognosis. Mitochondria play a central role in the energy metabolism of eukaryotic cells and can influence cell death mechanisms, which are critical in tumorigenesis and progression. However, the prognostic significance of the interplay between mitochondrial function and cell death in LGG requires further investigation. METHODS: We employed a robust computational framework to investigate the relationship between mitochondrial function and 18 cell death patterns in a cohort of 1467 LGG patients from six multicenter cohorts worldwide. A total of 10 commonly used machine learning algorithms were collected and subsequently combined into 101 unique combinations. Ultimately, we devised the mitochondria-associated programmed cell death index (mtPCDI) using machine learning models that exhibited optimal performance. RESULTS: The mtPCDI, generated by combining 18 highly influential genes, demonstrated strong predictive performance for prognosis in LGG patients. Biologically, mtPCDI exhibited a significant correlation with immune and metabolic signatures. The high mtPCDI group exhibited enriched metabolic pathways and a heightened immune activity profile. Of particular importance, our mtPCDI maintains its status as the most potent prognostic indicator even following adjustment for potential confounding factors, surpassing established clinical models in predictive strength. CONCLUSION: Our utilization of a robust machine learning framework highlights the significant potential of mtPCDI in providing personalized risk assessment and tailored recommendations for metabolic and immunotherapy interventions for individuals diagnosed with LGG. Of particular significance, the signature features highly influential genes that present further prospects for future investigations into the role of PCD within mitochondrial function.

An unusual case of acquired angioedema associated with monoclonal gammopathies of uncertain significance.

Acquired angioedema (AAE) is a rare disease due to the C1 esterase inhibitor (C1-INH) deficiency. Clinically, its symptoms are similar to hereditary angioedema (HAE) with hereditary C1-INH deficiency. Both conditions have the potential to cause upper airway obstruction, which can be fatal in clinical practice and thus require intense attention. Here, we'd like to discuss the clinical presentation, diagnosis and follow up of a special case of AAE associated with monoclonal gammopathies of unknown significance (MGUS) with recurrent upper airway obstruction. The patient was regularly followed up after being discharged from our ward. Measurements of C3-C4 levels were carried out by a hematological test. Due to the rarity of such a disease, especially in Chinese people, relevant diagnosis methods are missing in this patient, so the patient was only diagnosed with AAE-C1-INH associated with MGUS clinically. The latest follow up showed that he still underwent recurrent upper airway obstruction; thus, he remained in a tracheostomy state due to a lack of proper medication prophylaxis and died eventually. This unusual case reminds emergency physicians to pay attention to such disease during clinical practice, and relevant diagnosis method should be improved.

An unusual case of acquired angioedema associated with monoclonal gammopathies of uncertain significance

Acquired angioedema (AAE) is a rare disease due to the C1 esterase inhibitor (C1-INH) deficiency. Clinically, its symptoms are similar to hereditary angioedema (HAE) with hereditary C1-INH deficiency. Both conditions have the potential to cause upper airway obstruction, which can be fatal in clinical practice and thus require intense attention. Here, we’d like to discuss the clinical presentation, diagnosis and follow up of a special case of AAE associated with monoclonal gammopathies of unknown significance (MGUS) with recurrent upper airway obstruction. The patient was regularly followed up after being discharged from our ward. Measurements of C3–C4 levels were carried out by a hematological test. Due to the rarity of such a disease, especially in Chinese people, relevant diagnosis methods are missing in this patient, so the patient was only diagnosed with AAE-C1-INH associated with MGUS clinically. The latest follow up showed that he still underwent recurrent upper airway obstruction; thus, he remained in a tracheostomy state due to a lack of proper medication prophylaxis and died eventually. This unusual case reminds emergency physicians to pay attention to such disease during clinical practice, and relevant diagnosis method should be improved (AU)

Design and Optimization of Thermal Field for PVT Method 8-Inch SiC Crystal Growth.

As a wide bandgap semiconductor material, silicon carbide has promising prospects for application. However, its commercial production size is currently 6 inches, and the difficulty in preparing larger single crystals increases exponentially with size increasing. Large-size single crystal growth is faced with the enormous problem of radial growth conditions deteriorating. Based on simulation tools, the physical field of 8-inch crystal growth is modeled and studied. By introducing the design of the seed cavity, the radial temperature difference in the seed crystal surface is reduced by 88% from 93 K of a basic scheme to 11 K, and the thermal field conditions with uniform radial temperature and moderate temperature gradient are obtained. Meanwhile, the effects of different processing conditions and relative positions of key structures on the surface temperature and axial temperature gradients of the seed crystals are analyzed in terms of new thermal field design, including induction power, frequency, diameter and height of coils, the distance between raw materials and the seed crystal. Meanwhiles, better process conditions and relative positions under experimental conditions are obtained. Based on the optimized conditions, the thermal field verification under seedless conditions is carried out, discovering that the single crystal deposition rate is 90% of that of polycrystalline deposition under the experimental conditions. Meanwhile, an 8-inch polycrystalline with 9.6 mm uniform deposition was successfully obtained after 120 h crystal growth, whose convexity is reduced from 13 mm to 6.4 mm compared with the original scheme. The results indicate that the optimized conditions can be used for single-crystal growth.

Correlation between nutritional status screening by MNA-SF and acute stroke-associated infections in older adults.

PURPOSE: This study aimed to explore the correlation between nutritional status screening using the MNA-SF and stroke-associated infections (SAI) in older adults. METHODS: A retrospective study of patients aged over 70 years with acute stroke was conducted. The patients were divided into normal nutritional status, malnutrition risk, and malnutrition groups depending on their baseline MNA-SF scores. The correlation between nutritional status and SAI was identified using multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to demonstrate the predicted value of MNA-SF. RESULTS: 497 patients were included, 101 (20.32%) developed SAI. 32.29% of patients with malnutrition developed SAI, while 25.14% of those with malnutrition risk developed SAI. Malnutrition (aOR 4.58, 95% CI 2.34-8.96, p < 0.001) and risk of malnutrition (aOR 3.70, 95%CI 2.01-6.85, p < 0.001) were independent risk factors for SAI in older stroke patients. The area under the curve (AUC) value of MNA-SF was 0.713. CONCLUSION: MNA-SF is a simple and effective nutritional screening tool for predicting the occurrence of SAI in older patients with acute stroke.

Study on the relationship between genetic polymorphism of reductive folic acid carrier and the risk of neural tube defects.

BACKGROUND: To investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population. METHODS: The subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group). RESULTS: The levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father's exposure to organic solvents, folic acid deficiency, and mother's diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor. CONCLUSION: Folic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.

Epidemiology of pediatric central nervous system tumors in Uyghur: experience from a single center.

PURPOSE: Retrospective analysis of clinical and epidemiological characteristics of central nervous system (CNS)tumors in Uyghur children from a single center in Xinjiang. METHODS: Between January 2013 and December 2021, 243 children (0-17 years old) with a clear pathological type of CNS tumor are collected and analyzed for tumor size, grade, and category, as well as their relationship with the child's gender, age, and region of origin according to the 2021 edition of the new WHO CNS tumor classification. OUTCOME: The 243 cases of CNS tumors in Uyghur children are predominantly from rural areas, with 144 cases (59.26%) of supratentorial tumors and 129 cases (53.09%) of low-grade tumors. With an overall male-to-female ratio of 1.43:1, a peak age of incidence of 6 to 8 years. CONCLUDING: The present study is based on a 9-year analysis of pediatric CNS data from a single center, and the center is the largest tertiary hospital in Xinjiang with large numbers of admitted patients, which may reflect some extent the clinical characteristics and epidemiological features characteristics of pediatric CNS tumors in Uyghur in Xinjiang.

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brain metastases. This process can be plausibly explained by the "seed and soil" hypothesis, which essentially states that tumor cells can interact with various components of the central nervous system microenvironment to produce adaptive changes; it is this interaction that determines the development of brain metastases. As a novel form of intercellular communication, exosomes play a key role in the brain metastasis microenvironment and carry various bioactive molecules that regulate receptor cell activity. In this paper, we review the roles and prospects of brain metastatic tumor cells, the brain metastatic tumor microenvironment, and exosomes in the development and clinical management of brain metastases.

Study on Purification Technology of Silicon Carbide Crystal Growth Powder.

Silicon carbide (SiC) is a wide-bandgap (WBG) semiconductor material, and its preparation process has strict requirements on the purity of raw materials. A self-developed medium-frequency induction heating furnace was used to carry out powder heat treatment and purification experiments on SiC powder to improve the purity of the powder. Samples with 3.5N purity were analyzed using XRD and GDMS characterization methods. It was found that under conditions of high-temperature (2200 °C) and long-time (50 h) processing, the impurity removal effect was quite good, but the powder loss was as high as 53.42%. The powder loss during the low-temperature (less than 2050 °C) and short-time process was less than 1.5%, but the purification effect was not substantial. After a prolonged processing time, the purification effect of low-temperature heat treatment conditions was improved, but the powder loss was also increased to 30%. In contrast, segmented purification processing at a low temperature in the early stage and a high temperature in the later stage achieved a good purification effect. On the premise of maintaining the utilization rate of raw materials, a 5N-purity SiC source was successfully prepared. The test results show that the contents of free Si, free C and free oxygen impurities were reduced to less than 0.01%, and the contents of Al, B, Fe, Mg, Na, Ti and other impurities were less than 1.15 ppm, which is close to the ppb level.

Classification and Drug Resistance Analysis of Pathogenic Bacteria in Patients with Bacterial Pneumonia in Emergency Intensive Care Unit.

Objective: This study aimed to compare the identification efficiency of metagenome next generation sequencing (mNGS) and traditional methods in detecting pathogens in patients with severe bacterial pneumonia (BP) and further analyze the drug resistance of common pathogens. Methods: A total of 180 patients with severe BP who were admitted to our hospital from June 2017 to July 2020 were selected as the research objects. Alveolar lavage fluid from the patients were collected, and pathogens were detected by the mNGS technology and traditional etiological detection technology. Common pathogens detected by mNGS were tested for the drug sensitivity test. The difference between mNGS and traditional detection method in the identification of pathogenic bacteria in severe BP patients was compared, and the distribution characteristics and drug resistance of pathogenic bacteria were analyzed. Results: The positive rate of mNGS detection was 92.22%, which was significantly higher than that of the traditional culture method (58.33%, P < 0.05). 347 strains of pathogenic bacteria were detected by mNGS, including 256 strains of Gram-negative bacteria (G-), 89 strains of Gram-positive bacteria (G+), and 2 strains of fungi. Among G- bacteria, Acinetobacter baumannii had higher resistance to piperacillin/tazobactam, ceftazidime, imipenem, levofloxacin, amikacin, ciprofloxacin, gentamicin, and the lowest resistance to tigecycline. The resistance of Klebsiella pneumoniae to piperacillin/tazobactam and ceftazidime was higher. Pseudomonas aeruginosa had low resistance to all the drugs. Escherichia coli had high drug resistance to most drugs, and the drug resistant rates to cefoperazone/sulbactam, piperacillin/tazobactam, ceftazidime, imipenem, and gentamicin were all more than 50.00%. G+ bacteria had high resistance to penicillin, azithromycin, amoxicillin and levofloxacin, and amoxicillin and levofloxacin had high resistance, up to 100.00%. Conclusion: mNGS has high sensitivity for the identification of pathogenic bacteria in patients with BP. G- bacteria were the main pathogens of BP, but both G- and G+ bacteria had high resistance to a variety of antibacterial drugs.

The RPL4P4 Pseudogene Is a Prognostic Biomarker and Is Associated with Immune Infiltration in Glioma.

Objective: Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in gliomas. However, its biological function in gliomas remains unclear. Methods: In this study, we analyzed clinical data on patients with glioma obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx), and the GEPIA2 databases. We used the R language for the main analysis. Correlations among RPL4P4 expression, pathological characteristics, clinical outcome, and biological function were evaluated. In addition, the correlations of RPL4P4 expression with immune cell infiltration and glioma progression were analyzed. Finally, wound healing, Transwell, and CCK-8 assays were performed to analyze the function of RPL4P4 in glioma cells. Result: We found that RPL4P4 is highly expressed in glioma tissues and is associated with poor prognosis, IDH1 wild type, codeletion of 1p19q, and age. Multivariate analysis and the nomogram model showed that high RPL4P4 expression was an independent risk factor for glioma prognosis and had better prognostic prediction power. Moreover, high RPL4P4 expression correlated with immune cell infiltration, which showed a significant positive association with M2-type macrophages. Finally, RPL4P4 knockdown in glioma cell lines caused decreased glioma cell proliferation, invasion, and migration capacity. Conclusion: Our data suggest that RPL4P4 can function as an independent prognostic predictor of glioma. It also shows that RPL4P4 expression correlates with immune cell infiltration and that targeting RPL4P4 may be a new strategy for the treatment of glioma patients.

A bibliometrics analysis and visualization of osteoimmunology on osteoarthritis studies.

BACKGROUND: Osteoarthritis (OA), the most prevalent form of arthritis, which affects up to 15% of the adult population. The work presented in this paper focuses on the analysis of the publications on osteoimmunology of OA. The purpose of this paper is to provide inspiration for future research on osteoimmunology of OA. METHODS: We extracted all of the English publications relevant to osteoimmunology of OA published from 1991-2020 from the Web of Science. SPSS, GraphPad Prism, Citespace, and VOSviewer were utilized to collect and analyze the publication trends in osteoimmunology of OA. RESULTS: We identified a total number of 1,004 publications with a total number of citations of 35,675 by October 31, 2020. Most publications came from China (26.8%). The United States ranked second, but its average number of citations and H index ranked best (10,130 citations and 55 H-index). Shandong University is the main center of institutional cooperation. Most papers related to osteoimmunology of OA were published in the journal of Osteoarthritis and Cartilage. In this field, TAK PP published the most papers (15), while Kotake, S's article was cited the most frequently (1,195). As presented in Figure 6, the 70 keywords, defined as terms that appeared more than 50 times in all papers, were classified into four clusters molecular research, human research, animal research and cell research. Research on cytokines and pathways is the new trend in Molecular research. CONCLUSION: The current status and global trend of osteoimmunology of OA revealed by this study indicates that there is a strong possibility that the number of papers will increase in the coming year, and the research on cytokines as well as pathways would be the next hot topic.

Optimization of thermal field of 150 mm SiC crystal growth by PVT method.

The excellent physical properties of SiC as an electronic material determine its important application prospects, especially in the new-energy industry, but the preparation of large-sized materials with high quality is not easy. Therefore, the physical fields in the growth process were modeled and studied with the help of the numerical simulation software Virtual Reactor, and its accuracy was verified by the agreement between morphology of the experimental crystal and the simulation. Additionally, the effects of thermal insulation adjustment of crystal growth thermal fields, application of seed crystals with different diameters, and shelter structure on the crystal growth process were also studied. By optimizing the crystal growth conditions, a nearly flat and slightly convex crystal growth interface was obtained successfully in our lab. Crystal quality was significantly improved, and a 6-inch SiC crystal with single polytype, high quality and low defects was successfully prepared.

Study of Effect of Coil Movement on Growth Conditions of SiC Crystal.

SiC substrates have outstanding advantages over traditional materials in power device application, and are mainly prepared by a physical vapor transport method (PVT). Whether the PVT furnace works by resistance heating or induction heating, both face the problem of the deterioration of growth conditions during a long-term process. The relative position of the thermal field directly affects the crystal growth conditions, but the law of specific influence and the change in physical environment inside the thermal field have not been made sufficiently clear and lack systematic research. Therefore, SiC single crystal growth, with different directions and rates in the direction of movement of the heating module, was modeled using a simulation method, and the law of variation of the physical field, including heat flux, temperature, powder porosity and growth rate parameters under different schemes, was analyzed. The study indicates that the decay of raw materials is the primary reason why growth conditions cannot be maintained. The results verified that different coils' modes of movement have different effects on the improvement or adjustment of SiC crystals' growth conditions. Under the same temperature control conditions, the coils' movement rates of 200 µm/h, 0, -200 µm/h and -400 µm/h correspond to the average growth rates of 140, 152, 165 and 172 µm/h, respectively. The results show that downward displacement of the coils is beneficial in compensating for the deterioration of growth conditions, but it is easier to form convex surfaces and is not conducive to expanding diameter growth. This also verifies that the desired crystal growth state can be obtained by adjusting the position of the thermal field.

Repair of Cranial Defects in Rabbits with 3D-Printed Hydroxyapatite/Polylactic Acid Composites.

Objective: The safety and efficacy of three-dimensional- (3D-) printed hydroxyapatite/polylactic acid (HA-PLA) composites in repairing cranial defects were evaluated in a rabbit experimental model. Methods: Twelve New Zealand rabbits were selected as experimental subjects. Two holes (A and B), each with a diameter of approximately 1 cm, were made in the cranium of each rabbit. Hole A served as the experimental manipulation, and hole B served as the control manipulation. A 3D-printed HA-PLA composite was used for placement onto hole A, whereas autologous bone powder was used for placement onto hole B. Samples from the experimental holes and the control holes were collected at 30 and 90 days after surgery. The obtained materials were examined in terms of their morphologies and histopathologies and were also subjected to simultaneous hardness tests. Results: Both the 3D-printed HA-PLA composite and autologous bone powder were able to repair and fill the cranial defects at 30 days and 90 days after surgery. At 30 days after surgery, the microhardness of the area repaired by the HA-PLA composite was lower than that of the area repaired by autogenous bone powder (p < 0.01), but neither of these treatments reached the hardness of normal bone at this time (p < 0.01). At 90 days after surgery, there was no statistically significant difference in the microhardness of the repaired area from the 3D-printed HA-PLA composite compared with that of the repaired area from autologous bone powder (p > 0.05), and there was no statistically significant difference in the hardness of the two repaired areas compared with that of the normal bone (p > 0.05). Hematoxylin-eosin staining showed that bone cells in the HA-PLA material in the experimental group grew and were arranged in an orderly manner. Bone trabeculae and marrow cavities were formed on the pore surface and inside of the HA-PLA scaffold, and the arrangement of bone trabeculae was regular. Conclusion: 3D-printed HA-PLA composites can induce bone regeneration, are biocompatible, have the same strength as autologous bone powder, are able to degrade, and are ultimately safe and effective for repairing cranial defects in rabbits. However, further research is needed to determine the feasibility of 3D-printed HA-PLA composites in human cranioplasty.

Fault detection in switching process of a substation using the SARIMA-SPC model.

To detect substation faults for timely repair, this paper proposes a fault detection method that is based on the time series model and the statistical process control method to analyze the regulation and characteristics of the behavior in the switching process. As the first time, this paper proposes a fault detection model using SARIMA, statistical process control (SPC) methods, and 3σ criterion to analyze the characteristics in substation's switching process. The employed approaches are both very common tools in the statistics field, however, via effectively combining them with industrial process fault diagnosis, these common statistical tolls play excellent role to achieve rich technical contributions. Finally, for different fault samples, the proposed method improves the rate of detection by at least 9% (and up to 15%) than other methods.

C1q contributes to post-stroke angiogenesis via LAIR1-HIF1α-VEGF pathway.

Vascular remodeling is a critical event following a stroke. It is a well known fact that  C1q is the first molecule in the complement classical pathway. However, its role in the neovascularization that ocurs after a stroke, remains unclear. In this study, we investigated the effects of C1q on post-stroke angiogeneis in pMCAO rats. We found that increased C1q levels in IBZ enhanced angiogenesis in rats with pMCAO. C1q promoted viability and angiogenic function of RBMECs and HBMECs. Upregualtion of VEGF expression and secretion by C1q was also observed in RBMECs, HBMECs and in IBZ in pMCAO rats. Furthermore, we demonstrated that C1q enhanced angiogenic function of RBMECs through its receptor, LAIR1. The results show that administration of C1q enhanced neovascularization and reduced brain edema after pMCAO in rats. On the basis of these findings, we suggest that C1q plays an important role in post-stroke angiogenesis at least through LAIR- HIF1α-VEGF axis. C1q shows promise as a potential therapeutic candidate for stroke treatment.

Ultrasound-targeted microbubble enhances migration and therapeutic efficacy of marrow mesenchymal stem cell on rat middle cerebral artery occlusion stroke model.

To investigate the role of ultrasound-targeted microbubbles in the homing effect of bone marrow-derived mesenchymal stem cells (BMSCs) and in the therapeutic efficacy of BMSCs on the ischemic stroke. A middle cerebral artery occlusion (MCAO) model was induced by plug wire preparation. Seventy-two hours after MCAO, the treatment of BMSCs with ultrasound-targeted microbubble was assessed via modified neurological severity score (mNSS), infarct volumes, and cerebral edema. In addition, immunofluorescence was performed to analyze the homing effect of BMSCs with ultrasound-targeted microbubble. We find that BMSCs with ultrasound-targeted microbubble (BMMSCs with ultrasound-targeted microbubble [USMM] group) could significantly ameliorate mNSS, infarct volumes, and cerebral edema of MCAO compared with phosphate buffer saline group, BMSCs alone group (BMSC group), and BMSCs with Ultrasound group (Ultrasound group). Immunofluorescence analysis demonstrated that ultrasound-targeted microbubbles promoted the accumulation of BMSCs in rat MCAO brains. Our findings demonstrated that ultrasound-targeted microbubble could be an effective approach for the accumulation of BMSCs on ischemic stroke, and further improved the therapeutic efficacy of BMSCs on MCAO.