Overexpression of MTFR1 promotes cancer progression and drug-resistance on cisplatin and is related to the immune microenvironment in lung adenocarcinoma.

OBJECTIVE: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis. METHODS: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting. RESULTS: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC. CONCLUSIONS: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

HLA-DPA1 overexpression inhibits cancer progression, reduces resistance to cisplatin, and correlates with increased immune infiltration in lung adenocarcinoma.

PURPOSE: Human Leukocyte Antigen-DP alpha 1 (HLA-DPA1) is a critical gene in antigen-presenting cells and plays a significant role in immune regulation. The objective of this study was to comprehensively analyze the roles of HLA-DPA1 and its association with lung adenocarcinoma (LUAD). METHODS: We utilized bioinformatics and conducted a meta-analysis to examine the roles of HLA-DPA1 expression on the progression and immunity of LUAD. We also performed CCK-8, wound healing, and Transwell assays to validate the functions of HLA-DPA1 in LUAD. RESULTS: HLA-DPA1 expression is downregulated in LUAD tissues and is associated with gender, race, age, smoking history, clinical stage, histological type, lymph node metastasis, and prognosis of patients with LUAD. HLA-DPA1 is involved in immune responses, leukocyte cell-cell adhesion, and antigen processing and presentation. Overexpression of HLA-DPA1 inhibits cancer cell proliferation, migration, and invasion while promoting cell sensitivity to cisplatin in A549 and A549/DDP cells. Additionally, overexpression of HLA-DPA1 correlates with tumor purity, stromal, immune, and ESTIMATE scores, the abundance of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils), and immune cell markers (programmed cell death 1, cytotoxic T-lymphocyte-associated protein 4, and cluster of differentiation 8A). CONCLUSIONS: Decreased HLA-DPA1 expression is associated with poor prognosis and immune infiltration in LUAD while HLA-DPA1 overexpression inhibits cancer cell proliferation and progression. Therefore, HLA-DPA1 shows potential as a prognostic biomarker and a therapeutic target for LUAD.

CENPH overexpression promotes the progression, cisplatin resistance, and poor prognosis of lung adenocarcinoma via the AKT and ERK/P38 pathways.

Overexpression of centromere protein H (CENPH) promotes cancer growth and progression. However, the roles and underlying mechanisms have not been elucidated. Therefore, we aim to explore the roles and mechanisms of CENPH in lung adenocarcinoma (LUAD) progression by using comprehensive data analysis and cell experiments. In this study, the relationship between CENPH expression, which was obtained from the TCGA, and GTEx databases, and the prognosis and clinical characteristics of LUAD patients was analyzed, and the diagnostic values of CENPH was evaluated. CENPH-related risk models and nomograms were constructed to evaluate the prognosis of LUAD via Cox and LASSO regression analysis. The roles and mechanisms of CENPH in LUAD cells were studied using CCK-8 assay, wound healing and migration tests, and western blotting. The relationship between CENPH expression and immune microenvironment and RNA modifications was explored through correlation analysis. We found that CENPH was overexpressed in LUAD tissues, and tumors with diameter >3 cm, lymph node metastasis, distant metastasis, late stage, men, and dead cancer patients. Increased expression of CENPH was related to the diagnosis, poor survival rate, disease specific survival rate, and progression of LUAD. CENPH-related nomograms and risk models could predict the survival rate of LUAD patients. Inhibiting the expression of CENPH in LUAD cells decreased their migration, proliferation, and invasion, and promoted their sensitivity to cisplatin, which was related to the downregulation of p-AKT, p-ERK, and p-P38. However, there was no effect on AKT, ERK, and P38. Enhanced expression of CENPH was significantly correlated with immune score, immune cells, cell markers, and RNA modifications. In conclusion, CENPH was strongly expressed in LUAD tissues and was associated with poor prognosis, immune microenvironment, and RNA modifications. CENPH overexpression could enhance cell growth and metastasis and promote resistance to cisplatin via the AKT and ERK/P38 pathways, indicating its potential as a biomarker for the prognosis of LUAD.

A new prognostic model for RHOV, ABCC2, and CYP4B1 to predict the prognosis and association with immune infiltration of lung adenocarcinoma.

Background: Lymph node metastasis is one of the important factors affecting the prognosis of lung adenocarcinoma (LUAD) patients. The key molecules in lymph node metastasis have not yet been fully revealed. Therefore, we aimed to construct a prognostic model based on lymph node metastasis-related genes to evaluate the prognosis of LUAD patients. Methods: The differentially expressed genes (DEGs) in the process of LUAD metastasis were identified in The Cancer Genome Atlas (TCGA) database, and the biological roles of the DEGs were depicted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a protein-protein interaction (PPI) network. Survival analysis and Cox regression analysis were used to identify the genes related to the prognosis of patients with LUAD, and a nomogram and a prognostic model were constructed. The potential prognostic value, immune escape, and regulatory mechanisms of the prognostic model in LUAD progression were explored through survival analysis and gene set enrichment analysis (GSEA). Results: A total of 75 genes were upregulated, and 138 genes were downregulated in tissues of lymph node metastasis. The expression levels of STC1, CYP17A1, RHOV, GUCA2B, TM4SF20, DEFB1, CRHR2, ABCC2, CYP4B1, KRT16, and NTS were revealed as risk factors for a poor prognosis in LUAD patients. High-risk LUAD patients had a poor prognosis in the prognostic model based on RHOV, ABCC2, and CYP4B1. The clinical stage and the risk score were found to be independent risk factors for a poor prognosis in LUAD patients, and the risk score was associated with the tumor purity, T cell, natural killer (NK) cell, and other immune cells. The prognostic model might affect the progression of LUAD using DNA replication, the cell cycle, P53, and other signaling pathways. Conclusions: Lymph node metastasis-related genes RHOV, ABCC2, and CYP4B1 are associated with a poor prognosis in LUAD. A prognostic model based on RHOV, ABCC2, and CYP4B1 might predict the prognosis of LUAD patients and be associated with immune infiltration.

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam.

OBJECTIVE: We used the lateral fluid percussion injury (LFPI) model of moderate-to-severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post-traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI. METHODS: Adult male Sprague-Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post-LFPI, and were continuously video-EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post-LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d-to-7d neuroscore recovery, using machine learning. RESULTS: Low 2d plasma levels of Thr231 -phosphorylated tau protein (pTAU-Thr231 ) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam-treated LFPI rats were differentiated from vehicle treated by the 2d-HMGB1, 2d-pTAU-Thr231 , and 2d-UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle-treated LFPI rats: pTAU-Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle-treated LFPI rats). Levetiracetam-resistant early seizures were predicted by high 2d-IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d-to-7d neuroscore recovery was best predicted by higher 2d-S100B, lower 2d-HMGB1, and 2d-to-7d increase in HMGB1 or decrease in TNF (P < 0.05) (prognostic biomarkers). SIGNIFICANCE: Antiseizure medications and early seizures need to be considered in the interpretation of early post-traumatic biomarkers.

A new risk model for CSTA, FAM83A, and MYCT1 predicts poor prognosis and is related to immune infiltration in lung squamous cell carcinoma.

OBJECTIVES: To create a prognostic model based on differentially expressed genes (DEGs) in early lung squamous cell carcinoma (LUSC) and characterize the relationship between risk scores and tumor immune infiltration. METHODS: We identified DEGs in normal and tumor tissues that overlapped between LUSC-related data sets from the Gene Expression Omnibus and the Cancer Genome Atlas and evaluated their roles in the diagnosis and prognosis of LUSC by Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, meta-analysis and nomogram analysis. We then constructed a risk model based on Cox regression analysis and the Akaike information criterion and identified the relationship between LUSC risk scores and immune infiltration. RESULTS: Sixty-two overlapping DEGs were involved with keratinocyte differentiation, epidermal cell differentiation, neutrophil migration, granulocyte chemotaxis, granulocyte migration, leukocyte aggregation, and positive regulation of nuclear factor-κB (NF-κB) activity. Overexpression of family with sequence similarity 83 member A (FAM83A) and MYC target 1 (MYCT1), kallikrein related peptidase 8 (KLK8), and downregulation of ADP ribosylation factor like GTPase 14 (ARL14), caspase recruitment domain family member 14 (CARD14), cystatin A (CSTA), dickkopf WNT signaling pathway inhibitor 4 (DKK4), desmoglein 3 (DSG3), and keratin 6B (KRT6B) were associated with a poor prognosis in LUSC and had significant value for LUSC diagnosis. The expression of CSTA, FAM83A, and MYCT1 and high-risk scores were independent risk factors for a poor prognosis in LUSC. A risk nomogram revealed that risk scores could predict the prognosis of LUSC. The risk score was associated with neutrophils, naive B cells, helper follicular T cells, and activated dendritic cells. CONCLUSIONS: The expression levels of CSTA, FAM83A, and MYCT1 are related to the diagnosis and prognosis of LUSC and may have potential as therapeutic targets in LUSC. A risk model and nomogram based on CSTA, FAM83A, and MYCT1 can predict the prognosis of LUSC.

Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis.

Oxidative damage is a critical cause of diabetic wounds. Exosomes from various stem cells could promote wound repair. Here, we investigated the potential mechanism by which exosomes from adipose-derived stem cells (ADSC-EXOs) promote diabetic wound healing through the modulation of oxidative stress. We found that ADSC-EXOs could promote proliferation, migration, and angiogenesis in keratinocytes, fibroblasts, and endothelial cells. Furthermore, ADSC-EXOs reduced the reactive oxygen species (ROS) levels in these cells and protected them against hypoxic and oxidative stress damage. Finally, the local injection of ADSC-EXOs at wound sites significantly increased collagen deposition and neovascularization while reducing ROS levels and cell death; thus, it led to accelerated diabetic wound closure. The mechanism underlying ADSC-EXO functions involved heat-shock protein 90 (HSP90) expressed on the cell surface; these functions could be inhibited by an anti-HSP90 antibody. Exosomal HSP90 could bind to the low-density lipoprotein receptor-related protein 1 (LRP1) receptor on the recipient cell membrane, leading to activation of the downstream AKT signaling pathway. Knockdown of LRP1 and inhibition of the AKT signaling pathway by LY294002 in fibroblasts was sufficient to impair the beneficial effect of ADSC-EXOs. In summary, ADSC-EXOs significantly accelerated diabetic wound closure through an exosomal HSP90/LRP1/AKT signaling pathway.

Paired Box Gene 6 Regulates Heme Oxygenase-1 Expression and Mitigates Hydrogen Peroxide-Induced Oxidative Stress in Lens Epithelial Cells.

PURPOSE: This study aimed to investigate the regulation of heme oxygenase-1 (HO-1) by paired box gene 6 (Pax6) and their roles in hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in lens epithelial cells (LECs) (SRA01/04, HLE-B3). METHODS: Lens anterior capsule membranes of mice of different ages were obtained to compare differences in the expression of Pax6 and HO-1 using Western blotting. Pax6-overexpressing plasmid and small interfering RNA were designed to overexpress and silence Pax6, respectively. Cobalt protoporphyrin (CoPP) was used to promote the expression of HO-1. Oxidative damage in LECs was induced by treatment with H2O2 (400 µM) for 24 h. Cell viability was measured using the Cell Counting Kit-8 assay. Intracellular reactive oxygen species (ROS) were detected using flow cytometry and immunofluorescence. Superoxide dismutase (SOD) level was measured using SOD Assay Kit and apoptotic cells were quantified using annexin V-fluorescein isothiocyanate/propidium iodide staining. RESULTS: Pax6 and HO-1 expression levels showed an age-dependent decrease in LECs of mouse. Overexpressing Pax6 upregulated HO-1 expression level. Silencing Pax6 downregulated the HO-1 expression level, resulting in increased generation of ROS, reduced SOD activity, decreased cell viability, and increased apoptotic cells of LECs under H2O2-induced oxidative stress. Overexpressing Pax6 and CoPP both mitigates H2O2-induced oxidative stress by increasing the expression of HO-1 of LECs. CONCLUSION: Pax6 and HO-1 expression levels showed an age-dependent decrease in LECs in mouse anterior capsules. Pax6 could regulate the expression of HO-1 in LECs. The decrease of Pax6 weakened the antioxidant ability of LECs under H2O2-induced oxidative stress by downregulating HO-1, which may be a potential mechanism for the formation of age-related cataract.

An enhanced method for nucleic acid detection with CRISPR-Cas12a using phosphorothioate modified primers and optimized gold-nanopaticle strip.

CRISPR-Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid, portable and accurate features. However, cleavage of the amplicons and primers by the cis- and trans-activity of Cas12a hinders the attempts to integrate the amplification and detection into a single reaction. Through phosphorothioate modification of primers, we realized onepot detection with high sensitivity using plasmids of SARS-CoV-2, HPV16 and HPV18. We also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than others. By applying such reporters, the reaction time required for a lateral-flow readout was significantly reduced. Furthermore, to improve the specificity of the strip-based assay, we created a novel reporter and, when combined with a customized gold-nanopaticle strip, the readout was greatly enhanced owing to the elimination of the nonspecific signal. This established system, termed Targeting DNA by Cas12a-based Eye Sight Testing in an Onepot Reaction (TESTOR), was validated using clinical cervical scrape samples for human papillomaviruses (HPVs) detection. Our system represents a general approach to integrating the nucleic acid amplification and detection into a single reaction in CRISPR-Cas systems, highlighting its potential as a rapid, portable and accurate detection platform of nucleic acids.

A simple and rapid diagnostic method for 13 types of high-risk human papillomavirus (HR-HPV) detection using CRISPR-Cas12a technology.

Cervical carcinoma is the second most common cancer in women worldwide with greater than 99% of the cases caused by human papillomaviruses (HPVs). Early detection of HPVs especially the high risk types (HR-HPVs) are essential to prevent the disease progression. The existing methods for HPV detection, such as qPCR are of high sensitivity and specificity, but the need for expensive machinery and well-trained personnel slow down the disease detection. The emerging Cas12a-based method presents a new technique for nucleic acid detection. However, it is time-consuming and labor-intensive when used for HPV detection, as several reactions are required in order to identify multiple HPV infections. We herein present a non-genotyping method for 13 types of HR-HPV detection in a single reaction by combining the isothermal recombinase polymerase amplification (RPA) method with CRISPR-Cas12a technology. The result could be achieved in 35 min with high sensitivity (500 copies per reaction). This assay represents great advances for the application of RPA-Cas12a system and holds a great potential to address the key challenges facing the HPV diagnostics.

Can peritumoral regions increase the efficiency of machine-learning prediction of pathological invasiveness in lung adenocarcinoma manifesting as ground-glass nodules?

BACKGROUND: The peri-tumor microenvironment plays an important role in the occurrence, growth and metastasis of cancer. The aim of this study is to explore the value and application of a CT image-based deep learning model of tumors and peri-tumors in predicting the invasiveness of ground-glass nodules (GGNs). METHODS: Preoperative thin-section chest CT images were reviewed retrospectively in 622 patients with a total of 687 pulmonary GGNs. GGNs are classified according to clinical management strategies as invasive lesions (IAC) and non-invasive lesions (AAH, AIS and MIA). The two volumes of interest (VOIs) identified on CT were the gross tumor volume (GTV) and the gross volume of tumor incorporating peritumoral region (GPTV). Three dimensional (3D) DenseNet was used to model and predict GGN invasiveness, and five-fold cross validation was performed. We used GTV and GPTV as inputs for the comparison model. Prediction performance was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: The GTV-based model was able to successfully predict GGN invasiveness, with an AUC of 0.921 (95% CI, 0.896-0.937). Using GPTV, the AUC of the model increased to 0.955 (95% CI, 0.939-0.971). CONCLUSIONS: The deep learning method performed well in predicting GGN invasiveness. The predictive ability of the GPTV-based model was more effective than that of the GTV-based model.

Two miRNA prognostic signatures of head and neck squamous cell carcinoma: A bioinformatic analysis based on the TCGA dataset.

MicroRNAs(miRNAs) are maladjusted in multifarious malignant tumor and can be considered as both carcinogens and tumor-inhibiting factor. In the present study, we analyzed the miRNAs expression profiles and clinical information of 481 patients with head and neck squamous cell carcinoma (HNSCC) through the TCGA dataset to identify the prognostic miRNAs signature. A total of 114 significantly differentially expressed miRNAs (SDEMs) were identified, consisting of 60 up-adjusted and 54 down-adjusted miRNAs. The Kaplan-Meier survival method identified the prognostic function of 2 miRNAs (miR-4652-5p and miR-99a-3P). Univariate and multivariate Cox regression analyses indicated that the 2 miRNAs were significant prognostic elements of HNSCC. Furthermore, bioinformatic analysis was conducted by means of 4 online gene predicted toolkits to recognize the target genes, and enrichment analysis was performed on the target genes by DAVID. The outcomes depicted that target genes were correlated with calcium, as well as cell proliferation, circadian entrainment, EGFR, PI3K-Akt-mTOR, and P53 signaling pathways. Finally, the PPI network was conducted in view of STRING database and Cytoscape. Eight hub genes were identified by CytoHubba and MCODE app, respectively, CBL, SKP1, H2AFX, HGF, POLR2F, UBE2I, VAMP2, and GNAI2 genes. As a result, we identified 2 miRNAs signatures, 8 hub genes, and significant signaling pathways for estimating the prognosis of HNSCC. In order to further explore the molecular mechanism of HNSCC occurrence and development, more comprehensive basic and clinical studies are needed.

Lung Cancer Pathological Image Analysis Using a Hidden Potts Model.

Nowadays, many biological data are acquired via images. In this article, we study the pathological images scanned from 205 patients with lung cancer with the goal to find out the relationship between the survival time and the spatial distribution of different types of cells, including lymphocyte, stroma, and tumor cells. Toward this goal, we model the spatial distribution of different types of cells using a modified Potts model for which the parameters represent interactions between different types of cells and estimate the parameters of the Potts model using the double Metropolis-Hastings algorithm. The double Metropolis-Hastings algorithm allows us to simulate samples approximately from a distribution with an intractable normalizing constant. Our numerical results indicate that the spatial interaction between the lymphocyte and tumor cells is significantly associated with the patient's survival time, and it can be used together with the cell count information to predict the survival of the patients.

Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update.

Infantile spasms are the typical seizures of West syndrome, an infantile epileptic encephalopathy with poor outcomes. There is an increasing need to identify more effective and better tolerated treatments for infantile spasms. We have optimized the rat model of infantile spasms due to structural etiology, the multiple-hit rat model, for therapy discovery. Here, we test three compounds administered after spasms induction in the multiple hit model for efficacy and tolerability. Specifically, postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebral injections of doxorubicin and lipopolysaccharide. On PN5 p-chlorophenylalanine was given intraperitoneally (i.p.). Daily monitoring of weights and developmental milestones was done and rats were intermittently video monitored. A blinded, randomized, vehicle-controlled study design was followed. The caspase 1 inhibitor VX-765 (50-200 mg/kg i.p.) and the GABAB receptor inhibitor CGP35348 (12.5-100 mg/kg i.p.) each was administered in different cohorts as single intraperitoneal injections on PN4, using a dose- and time-response design with intermittent monitoring till PN5. 17ß-estradiol (40 ng/g/day subcutaneously) was given daily between PN3-10 and intermittent monitoring was done till PN12. None of the treatments demonstrated acute or delayed effects on spasms, yet all were well tolerated. We discuss the implications for therapy discovery and challenges of replication trials.

Therapeutic benefit of bone marrow-derived endothelial progenitor cell transplantation after experimental aneurysm embolization with coil in rats.

Aneurysm embolization with coil is now widely used clinically. However, the recurrence of aneurysms after embolization has always plagued neurosurgeons because the endothelial layer of the aneurysm neck loses its integrity after being embolized by coil. Bone marrow-derived endothelial progenitor cells (BM-EPCs) could be incorporated into injured endothelium and differentiate into mature endothelial cells during vascular repairing processes. The aim of our study is to explore the effects of BM-EPCs on aneurysm repairing and remodeling in a rat embolization model of abdominal aortic aneurysm. BM-EPC proliferation, migration and tube formation were not affected by super-paramagnetic iron oxide nanoparticle (SPIO) labeling compared to the controls (p>0.05). The number of SPIO-labeled cells greatly increased in EPC transplanted rats compared to that of phosphate buffered saline treated rats. SPIO-labeled EPC (SPIO-EPC) are mainly located in the aneurysm neck and surrounded by fibrous tissue. A histology study showed that the aneurysm orifice was closed with neointima and the aneurysm was filled with newly formed fibrous tissue. The SPIO-EPC accumulated in the aneurysm neck, which accelerated focal fibrous tissue remodeling, suggesting that BM-EPCs play a crucial role in repairing and remodeling the aneurysm neck orifice.

Silica-coated superparamagnetic iron oxide nanoparticles targeting of EPCs in ischemic brain injury.

Intravenous transplantation of endothelial progenitor cells (EPCs) reduced ischemic brain injury. However, less cell homing to damaged sites limited its functions. In present study, we labeled EPCs with silica-coated superparamagnetic iron oxide nanoparticles (SiO4@SPIONs) and applied exterior magnetic field to guide SiO4@SPIONs-labeled EPCs (SiO4@SPIONs-EPCs) to the ischemic hemisphere of the brain. We optimized SiO4@SPIONs labeling dose, which did not affect proliferation, migration and tube formation of EPCs in vitro. SiO4@SPIONs-EPCs homing was greatly increased in ischemic hemisphere with magnetic field treatment in mice underwent transient middle cerebral artery occlusion (tMCAO). Injection of SiO4@SPIONs-EPCs and followed by magnetic field treatment showed improved neurobehavioral outcomes, reduced brain atrophic volume, increased microvessel density and VEGF expression in the ischemic perifocal region compared to groups without magnetic field treatment (p < 0.05). Our results demonstrated that exterior magnetic field could guide SiO4@SPIONs-EPCs to ischemic region and enhance therapeutic effect, suggesting that magnetic-guided SiO4@SPIONs-EPCs delivery is a promising approach in cerebral ischemic therapy.

The invention of an iliosacral screw fixation guide and its preliminary clinical application.

OBJECTIVE: To introduce an iliosacral screw fixation guide and evaluate its efficacy in fixation of sacroiliac joint fracture-dislocations. METHODS: Between January 2011 and May 2011, eight patients (five men, three women) with sacroiliac joint fracture-dislocation underwent percutaneous iliosacral screw fixation with the assistance of this minimally invasive guide and under CT guidance. The patients, aged from 26 to 56 years (mean 32 years), had vertically unstable pelvic fractures. Before surgery, six patients who had displacement of >2 cm in their sacroiliac joints underwent skeletal traction on the femoral condyle. The inserted sites were marked out on the affected side of their buttocks after the best screw trajectory had been determined under CT control. The gear that controls the direction of the minimally invasive guide was adjusted according to the inserting angle determined by CT scans. A K-wire was inserted into the sacroiliac joint along the pilot sleeve of the guide, and a hollow screw (diameter 7.3 mm) was implanted into the sacroiliac joint along the K-wire. RESULTS: All eight operations were successful on the first attempt. The operations lasted from 10 to 20 minutes (mean 14 minutes). Immediate CT scans confirmed that all the screws had been placed in the desired positions, none had penetrated the bones and the configuration of the sacroiliac joints had been satisfactorily restored and firmly fixed. No patient experienced numbness or radiating pain in the lower limbs during surgery. There were no postoperative vascular or neurological complications. CONCLUSION: The minimally invasive guide can eliminate discrepancies resulting from the surgeon's own sensory input when inserting screws under the guidance of CT, making percutaneous iliosacral screw fixation more accurate, safe and simple.