Assessment of the sacroiliac joint in patients with axial spondyloarthritis via three-dimensional ultrashort echo time magnetic resonance imaging.

Background: Bone erosion in the sacroiliac joint (SIJ) is highly specific for the diagnosis of axial spondyloarthritis (axSpA) and may indicate early disease progression. The 3D ultrashort echo time (3D-UTE) technique excels in providing clear contrast between the articular cartilage and the bone cortex interface. Additionally, it is emerging as a promising quantitative tool for detecting early cartilage changes. Therefore, this study aimed to evaluate the diagnostic performance of 3D-UTE sequences in identifying bone erosion in the SIJ of patients with axSpA and to clarify the potential of cartilage T2* values as a quantitative biomarker for axSpA. Methods: This prospective study employed convenience and consecutive sampling methods to recruit patients diagnosed with axSpA in Peking University Third Hospital who met the Assessment of Spondyloarthritis International Society (ASAS) criteria and also an equal number of healthy volunteers. After providing informed consent, all participants underwent 3D-UTE sequences and conventional T2* mapping of the SIJs. Two radiologists separately interpreted the bone erosion of each SIJ on 3D-UTE sequences. Erosion detection of SIJs via computed tomography (CT) served as the standard of reference. The T2* values of the cartilage were measured and compared, and the diagnostic efficacy of the T2* value for axSpA diagnosis was evaluated. Results: A total of 32 patients and 32 healthy volunteers were included. The 3D-UTE sequence, as separately assessed by two reviewers in terms of its ability to detect erosions, exhibited a notable level of accuracy. For the two reviewers, the respective diagnostic sensitivities were 94.7% and 92.9%, the specificities were 97.4% and 96.5%, positive predictive values were 96.7% and 95.4%, the negative predictive values were 95.9% and 94.5%, the accuracies were 96.2% and 94.9%, and the areas under the curve (AUCs) were 96.1% and 94.7%. For the detection of erosions, the interreader κ value was 0.949. The T2* values of the SIJ cartilage were significantly higher in patients with axSpA than in healthy volunteers. The intraobserver intraclass correlation coefficients (ICCs) for T2* measurements ranged between 80.5% and 82.2%. Meanwhile, the interobserver ICCs for UTE-T2* and gradient echo T2* measurements were 81.5% and 80.8%, respectively. The AUCs of the UTE-T2* values for discriminating patients with axSpA from the healthy volunteers of the two readers were 73.3% and 71.6%, respectively. Conclusions: 3D-UTE sequences can be used as a reliable morphological imaging technique for detecting bone erosion in the SIJ. Additionally, UTE-T2* values of the cartilage may offer a quantitative method for identifying patients with axSpA.

ELL associated factor 2 is a potential diagnostic and prognostic indicator: evidence from the in silico and in vitro experiments.

Due to the lack of sensitive biomarkers, cancer disease kill 9.6 million individuals each year around the globe. The present study aimed to explore the association between ELL Associated Factor 2 (EAF2) expression and its diagnostic and prognostic landscape across different human cancers using an in silico and in vitro approach. To achieve the defined goals of this study, we used the following online sources: UALCAN, KM plotter, TNMplot, cBioPortal, STRING, DAVID, MuTarget, Cytoscape, and CTD. In addition to this, we also used additional The Cancer Genome Atlas (TCGA) datasets via TIMER2, GENT2, and GEPIA to confirm the expression of EAF2 on additional cohorts. Finally, we performed RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques-based analysis using A549, ABC-1, EBC-1, LK-2 lung cancer cell lines, and MRC-9 normal control lung cell line for further validation of the results. On balance, EAF2 was elevated in 19 types of human cancers and its up-regulation was significantly correlated with shorter overall survival (OS), relapse-free survival (RFS), and metastasis in Liver Hepatocellular Carcinoma (LIHC) and Lung Squamous Cell Carcinoma (LUSC) patients. We further evaluated that EAF2 expression was also elevated across LIHC and LUSC patients belonging to different clinicopathological features. Through pathway analysis, EAF2 associations were observed with four important pathways. Moreover, some worth noticing correlations were also documented between EAF2 expression and its promoter methylation level, genetic alterations, other mutant genes, tumor purity, and different immune cells infiltration. The higher EAF2 expression contributes significantly to the tumorigenesis and metastasis of LIHC and LUSC. Therefore, it can be used as a common biomarker in these cancers.

Imaging features of spinal fractures in ankylosing spondylitis and the diagnostic value of different imaging methods.

BACKGROUND: Our study aimed to characterize the imaging appearance of spinal fractures in ankylosing spondylitis (AS) and identify situations in which the use of magnetic resonance imaging (MRI) is necessary. METHODS: A total of 70 cases of spinal fractures associated with AS were retrospectively enrolled. Two radiologists independently reviewed the preoperative images. The location, type, ligament injury, neurological injury, and epidural hematoma following spinal fractures were assessed. RESULTS: Only one patient had a vertebral compression fracture, and 69 patients had 77 transverse fractures involving three columns. The most frequent injuries in AS patients were type B3 (N=32, 43.8%) spine fractures, followed by type C (N= 20, 27.4%) spine fractures. There were significant differences in fracture types of the different spine regions (H=14.1, P<0.0001). Most type C spine fractures were located in the lower cervical spine, while most of the type B2 spine fractures were located in the thoracic spine. Transverse fractures were classified as shear or stress type fractures. In total, there were 62 shear fractures and 15 stress fractures. All of the transverse fractures were detected by computed tomography (CT). The accuracy of CT in the diagnosis of the exact anatomic involvement of transverse fractures was significantly higher than that of MRI (χ2=8.36, P=0.014). The anterior longitudinal ligament (ALL) was the most frequently torn ligament. Tears of ossified ligaments were best visualized by sagittal reformatted CT. Lower cervical fractures were more likely to be associated with neurological injury compared with fractures to other regions of the spine (χ2=7.24, P=0.025). There were six epidural hematoma cases, which were only detected by MRI, were found to have fractures of the lower cervical spine. CONCLUSIONS: We recommend a whole-spine CT examination with three-dimensional reconstruction for detecting a suspected fracture in AS patients. In cases with neurological injury, MRI examinations are always mandatory. AS patients with lower cervical spine fractures require further investigation by MRI. Patients with non-lower cervical spine fractures without any neurological deficits do not need to undergo an immediate MRI.

Traceable metallic antigen release for enhanced cancer immunotherapy.

Tumor vaccine has shown outstanding advantages and good therapeutic effects in tumor immunotherapy. However, antigens in tumor vaccines can be easily cleared by the reticuloendothelium system in advance, which leads to poor therapeutic effect of tumor vaccines. Moreover, it was still hard to monitor the fate and distribution of antigens. To address these limitations, we synthesized a traceable nanovaccine based on gold nanocluster-labeled antigens and upconversion nanoparticles (UCNPs) for the treatment of melanoma in this study. PH-sensitive Schiff base bond is introduced between UCNPs and gold nanocluster-labeled ovalbumin antigens for monitoring antigens release. Our studies demonstrated that UCNPs conjugated metallic antigen showed excellent biocompatibility, pH-sensitive and therapeutic effect.

Synthesis, Characterization and Biological Evaluation of Magnolol and Honokiol Derivatives with 1,3,5-Triazine of Metformin Cyclization.

Herein, we sought to evaluate the contribution of the 1,3,5-triazine ring through the metformin cyclization unit to the biological activity of magnolol and honokiol-conjugates. One of the phenolic OH groups of magnolol or honokiol was replaced by a 1,3,5-triazine ring to further explore their synthesis and medicinal versatility. In this study, a robust procedure of three steps was adopted for the synthesis of magnolol and honokiol derivatives by alkylation of potassium carbonate with a 1,3,5-triazine ring. To our knowledge, this is the first report to connect one of the phenolic OH positions of magnolol or honokiol to a 1,3,5-triazine ring cyclized by metformin. The structural characterization of three new compounds was carried out via spectroscopic techniques, i.e., 13C NMR, 1H NMR, and HRMS. Surprisingly, these compounds showed no cytotoxicity against RAW 264.7 macrophages but significantly inhibited the proliferation of MCF-7 (human breast cancer cells), HepG2 (human hepatoma cells), A549 (human lung carcinoma cells), and BxPC-3 (human pancreatic carcinoma cells) tumor cell lines. Furthermore, the compounds also significantly inhibited the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the lipopolysaccharide (LPS)-activated mouse cells (RAW 264.7). Among them, compound 2 demonstrated promising broad-spectrum antiproliferative potential with half inhibitory concentration (IC50) values ranging from 5.57 to 8.74 µM and it significantly decreased caspase-3 and Bcl-2 expression in HepG2 cells. These interesting findings show that derivatization of magnolol and honokiol with 1,3,5-triazine affects and modulates their biological properties.

Prodrug-Based Nanoreactors with Tumor-Specific In Situ Activation for Multisynergistic Cancer Therapy.

Efficient drug delivery into tumor cells while bypassing many biological barriers is still a challenge for cancer therapy. By taking advantage of the palladium (Pd)-mediated in situ activation of a prodrug and the glucose oxidase (GOD)-based ß-d-glucose oxidation reaction, we developed a multisynergistic cancer therapeutic platform that combined doxorubicin (DOX)-induced chemotherapy with GOD-mediated cancer-orchestrated oxidation therapy and cancer starvation therapy. In the present work, we first synthesized DOX prodrugs (pDOXs) and temporarily assembled them with ß-cyclodextrins to reduce their toxic side effects. Then, a nanoreactor was constructed by synthesizing Pd0 nanoparticles in situ within the pores of mesoporous silica nanoparticles for the conversion of pDOX into the active anticancer drug. Furthermore, GOD was introduced to decrease the pH of the tumor microenvironment and induce cancer-orchestrated oxidation/starvation therapy by catalyzing ß-d-glucose oxidation to form hydrogen peroxide (H2O2) and gluconic acid. Our study provides a new strategy that employs a cascade chemical reaction to achieve combined orchestrated oxidation/starvation/chemotherapy for the synergistic killing of cancer cells and the suppression of tumor growth.

The binding mechanism of nitroreductase fluorescent probe: Active pocket deformation and intramolecular hydrogen bonds.

Nitroreductase (NTR), a member of the flavoenzyme family, could react with nicotinamide adenine dinucleotide by reducing nitro to amino at hypoxic tumor, which can be monitored by some fluorescent probes in vivo. Here, molecular docking and molecular dynamics simulation techniques were used to explore the molecular mechanisms between NTR and probes. The results showed that formation of hydrogen bond in 1F5V-13 between A@His215 and B@Ser41 with 74.53% occupancy might be the main reason for the decrease of probe fluorescence emission in experiment. Moreover, Probe 16 was rotated by nearly 60 degrees with respect to the position of other probes in protein binding pocket, deforming the protein active pocket, changing the hydrogen bond formation, which leads to the fluorescence performance of 16 with electron donor and electron acceptor groups was superior to other probes in experiment. The deformation of protein active pocket and the formation of intramolecular hydrogen bonds revealed the difference in performance of NTR fluorescent probe at molecular level, which provide theoretical guidance for latter design of fluorescent probes with better performance.

Lipidomics Analysis of Timosaponin BII in INS-1 Cells Induced by Glycolipid Toxicity and Its Relationship with Inflammation.

Anemarrhena asphodeloides Bunge is a traditional Chinese medicine. The timosaponin BII is one of the most abundant and widely studied active ingredients in Anemarrhena asphodeloides Bunge. Related studies have shown that timosaponin BII has potential value for development and further utilization. The protective effect of timosaponin BII on islet ß cells under type 2 diabetes was investigated in the glycolipid toxic INS-1 cell model and possible biomarkers were explored by lipidomics analysis. Timosaponin BII was isolated from Anemarrhena asphodeloides Bunge by polyamide resin and Sephadex LH-20. Then, the glycolipid toxicity INS-1 cell model was established to investigate the protective effect of timosaponin BII. The results showed that timosaponin BII could significantly influence the levels of malondialdehyde (MDA) and glutathione (GSH), thereby restoring the insulin secretion ability and cell viability of model cells. Lipidomics analysis was combined with multivariate statistical analysis for marker selection. The four most common pathological and pharmacological lipid markers were phosphatidylserine (PS), suggesting that timosaponin BII had protective effects on model cells related to the reduction oxidative stress and macrophage inflammation. RAW264.7 macrophages were stimulated by LPS to establish a model of inflammation and study the effect of timosaponin BII on the nodes of NOD-like receptor P3 (NLRP3) inflammasome pathway in the model cells. In conclusion, timosaponin BII may have the effect of protecting INS-1 pancreatic ß cells through reducing IL-1ß (interleukin-1ß) production by inhibiting the NLRP3 inflammasome in macrophage and restoring the insulin secretion ability and cell viability by reducing oxidative stress.

Value of Apparent Diffusion Coefficient (ADC) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) in Differentially Diagnosing Angiomatous Meningiomas and Solitary Fibrous Tumors/Hemangiopericytomas.

BACKGROUND To determine if ADC and DCE-MRI can be used to differentiate angiomatous meningiomas (AMs) from solitary fibrous tumors/hemangiopericytomas (SFT/HPCs). MATERIAL AND METHODS We retrospectively reviewed records of 103 patients from 1 January 1 2014 to 1 November 2018. We enrolled 41 patients who had undergone a 3T MRI, with histologically confirmed AMs in 20 (48.80%) patients, and SFT/HPCs in 21 (51.20%) patients. The ADC and DCE-MRI features were derived and then compared by 2 independent-samples t tests and Wilcoxon rank sum test to obtain the ROC. RESULTS AMs had significantly lower ADC values than did SFT/HPCs, but AMs had significantly higher MCER values than did SFT/HPCs. A threshold value of 1.03×10⁻³ mm²/s for ADC to predict AMs from SFT/HPCs was estimated (AUC=0.902, sensitivity=88.20%, specificity=83.30%). Optimal diagnostic performance (AUC=0.825, sensitivity=84.60%, specificity=81.80%) was obtained when setting MCER=226.7% as the threshold value. CONCLUSIONS The ADC values of AMs were lower than those of SFT/HPCs; the MCER of AMs were greater than those of SFT/HPCs, and ADC was more useful than MCER, and these parameters could help diagnosis.

Histogram Analysis Parameters ADC for Distinguishing Ventricular Neoplasms of Ependymoma, Choroid Plexus Papilloma, and Central Neurocytoma.

BACKGROUND To determine if histograms of ADC can be used to differentiate ventricular ependymomas, choroid plexus papillomas (CPPs), and central neurocytomas (CNCs). MATERIAL AND METHODS We retrospectively reviewed records from 185 patients from 1 January 2014 to 1 November 2018. We finally included a total of 60 patients: 36 (60.00%) had histologically confirmed ependymomas, 10 (16.67%) had CPPs, and 14 (23.33%) had CNCs, as determined by routine MRI scanning at 3.0T. The ADC histogram features were derived and then compared by Kruskal-Wallis test (they were not normally distributed). Bonferroni test was used to compare the 2 groups and then we determined the ROC. RESULTS Ependymomas had significantly higher mean, perc.01%, perc.10%, perc.50%, perc.90%, and perc.99% than CNCs. Ependymomas had significantly lower skewness than CNCs. Histogram metrics derived from mean, perc.01%, perc.10%, perc.50%, and perc.90% were significantly lower in the CNCs group than in the CPPs group. CPPs showed significantly lower skewness than CNCs. A threshold value of 86.50 for perc.50% to predict ependymomas from CNCs was estimated (AUC=0.97, sensitivity=97.20%, specificity=85.70%). Optimal diagnostic performance to predict CPPs from CNCs (AUC=0.96, sensitivity=100.00%, specificity=85.70%) was obtained when setting Perc.50%=84.00 as the threshold value. CONCLUSIONS The ADC histogram analysis may help to discriminate ependymomas, CPPs, and CNCs.

Mesoporous Platinum Nanotherapeutics for Combined Chemo-photothermal Cancer Treatment.

Recently, nanoparticles that possess combined use in synergistic therapy, real-time imaging, and spatiotemporally controlled therapies have attracted enormous attention. Herein, we fabricated Doxorubicin (DOX)-loaded and ß-cyclodextrin (ß-CD)-capped mesoporous platinum nanoparticles (MPNPs) (DOX/MPNPs-AD-CD) for combined chemo-photothermal cancer therapy. DOX/MPNPs-AD-CD with high photothermal effect and loading rate could release the anticancer drugs stimulated by acidic tumor microenvironment or near-infrared light. Moreover, acid-degradable MPNPs would release cytotoxic Pt2+, which would enhance the efficiency of chemotherapy. In addition, the inherent photoacoustic and photothermal imaging can effectively guide chemo-photothermal therapy to achieve the desired treatment. Taken together, DOX/MPNPs-AD-CD possess the abilities of combined chemo-photothermal therapy and dual-imaging properties. The studies demonstrated that DOX/MPNPs-AD-CD could effectively inhibit tumor cell growth in vivo and in vitro. Thus, this treatment platform is expected to be one of interest for the clinical treatment of cancers.

Development of monoclonal antibodies against Sj29 and its possible application for schistosomiasis diagnosis.

OBJECTIVE: Timely Schistosoma japonicum detection improves outcomes in schistosomiasis. Here, we established a double antibody sandwich ELISA to detect Schistosoma japonicum. METHODS: Sj29 polyclonal and monoclonal antibodies were developed and identified. A Sj29 double antibody sandwich ELISA was evaluated. RESULTS: Assay sensitivity for detecting Schistosoma japonicum circulating antigen Sj29 was 76.7% (23/30), 54.5% (18/33) and 50.0% (18/36) in patients with acute, chronic and advanced schistosomiasis. No false positives or cross-reactivity was observed in healthy controls or patients with clonorchiasis, paragonimiasis, or ancylostomiasis, respectively. By contrast, false positives (5.7%) and cross-reactivity (6.5%-10%) were detected using an AWA-ELISA. The circulating antigen positive rates decreased significantly faster than that of the antibody detection after 6 months treatment (22.2%, 4/18 and 88.9%, 16/18). Chi-Square Tests revealed that Sj29 sandwich ELISA had lower sensitivity than AWA indirect ELISA in the detection of S. japonicum infected patients (p<0.05). Although our assay detection specificity in patients infected with other parasites or healthy controls appeared higher, the difference between the assays was insignificant. However, our assay showed significantly better results in monitoring praziquantel therapeutic effects (p=0.001), with antigen-positive rates decreasing significantly faster than antibody detection rates after 6 months of treatment (22.2%, 4/18 versus 88.9%, 16/18). CONCLUSIONS: Sj29 double antibody sandwich ELISA was established. The specificity of this method for detecting healthy sera was 100%. Meanwhile, Sj29 sandwich ELISA may have a potential diagnostic capability to distinguish current from past infections and assess drug treatment responses.

Preoperative Evaluation of the Grade and Stability of Osteochondritis Dissecans of the Knee by Magnetic Resonance Imaging.

Objective To assess the diagnostic performance of magnetic resonance imaging (MRI) in the grading of osteochondritis dissecans (OCD) of the knee.Methods Totally 47 patients with OCD of the knee confirmed by arthroscopy were retrospectively enrolled in this study.The OCD lesions were classified into four stages according to classification system of the International Cartilage Repair Society.Two radiologists analyzed all MRI findings independently,and the results were compared with those of arthroscopy.Sensitivity,specificity,and accuracy were calculated.Kappa value were calculated to quantify inter-observer agreement of the diagnostic OCD grade between two doctors by MRI.Specificity,sensitivity,and accuracy of MRI criteria indicating instability for detection of OCD instability were calculated.Results Of these 47 patients with 48 OCD lesions,stages Ⅰ,Ⅱ,Ⅲ,and Ⅲ lesions were detected in 4,8,16,and 20 patients,respectively.The specificity,sensitivity,and accuracy for the diagnosis of OCD stability were 75.0% (83.3%),88.9% (86.1%),and 85.4% (85.4%) for observer l (2),and the agreement of OCD grade between these two readers was substantial with a Kappa value of 0.82.The specificity,sensitivity,and accuracy of MRI criteria for the detection of OCD instability including high T2 signal intensity at the interface between the OCD and the underlying bone,multiple cysts or a single cyst of>5 mm in diameter surrounding OCD lesions,high T2 signal intensity cartilage fracture line traversing the articular cartilage,and osteochondral defect were 83.3%,80.6%,and 81.3%;75.0%,72.2%,and 72.9%;66.7%,69.4%,and 68.8%;100%,86.1%,and 89.6%,respectively. Conclusions Osteochondral defect is the most specific MRI sign for diagnosing instable OCD of the knee,whereas osteochondral fracture line has the lowest accuracy.MRI is a useful method to evaluate the grade and stability of OCD of the knee.

[Effect of BD Regimen Combined with Cyclophosphamide and Pirarubicin in Treatment of Relapse/Refractory Multiple Myeloma].

OBJECTIVE: To compare the efficacy and safety of BD regimen combined with cyclophosphamide(CTX) and pirarubicin chemotherapy(P-CAD) for patients with relapse/refractory multiple myeloma(MM). METHODS: Twenty-eight cases of relapse/refractory MM were enrolled in a group of P-CAD regimen, 36 cases of relapse/retractory MM treated with BD were used as controls. The therapeutic efficacy and adverse reactions of 2 regimens for patients with relapse/retractory MM were compared and analyzed. RESULTS: The overall response rate (CR+NCR+PR+MR) of the 28 cases treated with P-CAD regimen was 85.7%, and the response rate (CR+PR) was 75.0%. The median progression-free survival time were 16.1 months, and the average survival time were 30.6 months, while the overall response rate of the 36 patients treated with BD regimen was 63.9%, and the response rate was 55.6%. The median progression-free survival time were 13.7 months, and the average survival time were 26.7 months. The adverse reactions of 2 groups included gastrointestinal reactions, peripheral neuropathy, fatigue, skin rashes, leucopenia and thrombocytopenia, and they were all well tolerated. CONCLUSION: BD regimen combined with cyclophosphamide and pirarubicin chemotherapy can improve the response rate of patients with relapse/refractory multiple myeloma, and shows the trend of prolonging PFS and survival times. Patients were well tolerated, and this regimen is a new choice in treatment of relapse/refractory MM.

[Ligustrazine Promoted the Migration of Bone Marrow Mesenchymal Stem Cells by Up-regulating MMP-2 and MMP-9 Expressions].

OBJECTIVE: To explore the effect of ligustrazine on the migration of bone marrow mesenchymal stem cells (BMSCs) and protein expressions of matrix metalloproteinase-2 and-9 (MMP-2 and MMP-9) in vitro. METHODS: BMSCs were in vitro isolated and cultured using whole bone marrow adherent method, and phenotypes [surface positive antigens (CD29 and CD90) and negative antigens (CD34 and CD45)] identified using flow cytometry. BMSCs were divided into the blank control group, 25, 50, 100 µmol/L ligustrazine group, and the GM6001 group (100 µmol/L ligustrazine +MMPs inhibitor GM6001 ). The migration of BMSCs was tested by Transwell chamber test and wound healing assay after treated with ligustrazine for 24 h. The protein expressions of MMP-2 and MMP-9 were detected by Western blot. RESULTS: The third passage BMSCs grew well in uniform morphology. The expression rate of CD29, CD90, CD34, and CD45 was 96.9%, 97.3%, 0.2%, and 3.0%, respectively. Compared with the blank control group, the number of migrated cells and relative distance of cell invasion increased, and the protein expressions of MMP-2 and MMP-9 were elevated in each ligustrazine group (P < 0.05, P < 0.01). Compared with 100 µmol/L ligustrazine group, the number of migrated cells and relative distance of cell invasion decreased in 25 and 50 µmol/L ligustrazine groups and the GM6001 group (P < 0.01). Protein expression of MMP-2 decreased in 25 and 50 µmol/L ligustrazine groups (P < 0.01). CONCLUSION: Ligustrazine could promote the migration of BMSCs in vitro, and its mechanism might be related to up-regulating expression levels of MMP-2 and MMP-9 protein.

Therapeutic efficacy of umbilical cord-derived mesenchymal stem cells in patients with type 2 diabetes.

Type 2 diabetes (T2D) is characterized by progressive and inexorable ß-cell dysfunction, leading to insulin deficiency. Novel strategies to preserve the remaining ß-cells and restore ß-cell function for the treatment of diabetes are urgently required. Mesenchymal stem cells (MSCs) have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. The aim of the present clinical trial was to assess the safety and efficacy of umbilical cord-derived MSC (UCMSC) transplantation for patients with T2D. The safety and efficacy of UCMSC application were evaluated in six patients with T2D during a minimum of a 24-month follow-up period. Following transplantation, the levels of fasting C-peptide, the peak value and the area under the C-peptide release curve increased significantly within one month and remained high during the follow-up period (P<0.05). Three of the six patients became insulin free for varying lengths of time between 25 and 43 months, while the additional three patients continued to require insulin injections, although with a reduced insulin requirement. Fasting plasma glucose and 2-h postprandial blood glucose levels were relatively stable in all the patients following transplantation. There was no immediate or delayed toxicity associated with the cell administration within the follow-up period. Therefore, the results indicated that transplantation of allogeneic UCMSCs may be an approach to improve islet function in patients with T2D. There were no safety issues observed during infusion and the long-term monitoring period.

[Buyang Huanwu decoction promotes neuroblast migration from subventricular zone via inducing angiogenesis after ischemia].

OBJECTIVE: To study the effect of Buyang Huanwu decoction (BYHWD) inducing angiogenesis on the neuroblast migration from the subventricular zone and its mechanisms after focal cerebral ischemia. METHOD: The middle cerebral artery occlusion (MCAO) was performed to mice for 30 minutes to establish the model. The rats were divided into sham group, model group, BYHWD group and endostatin group. BYHWD (20 g x kg(-1), ig) and endostatin (10 µg, sc) were administered 24 h after ischemia once a day for consecutively 14 days. At 14 d after ischemia, the density of micro-vessel and the number of neuroblasts in the ischemia border zone were determined by immunofluorescence staining. The mRNA and protein expression of cell-derived factor-1 (SDF-1) and brain-derived neurotrophic (BDNF) were examined by real-time PCR and Western blot. RESULT: Compared with the model group, BYHWD significantly increased the density of micro-vessel and the number of DCX positive cells in the ischemia border zone (P < 0.01), and significantly increased the SDF-1 and BDNF mRNA and protein expression (P < 0.01). Compared with BYHWD group, endostatin significantly reduced the density of micro-vessel and the number of DCX positive cells in the ischemia border zone (P < 0.01), as well as the SDF-1, BDNF mRNA and protein expression (P < 0.01). CONCLUSION: BYHWD could promote the neuroblast migration from the subventricular zone via inducing angiogenesis after cerebral ischemia, the mechanism may be correlated with up-regulating the expression of SDF-1 and BDNF.

Expression and clinical significance of miRNA-34a in colorectal cancer.

BACKGROUND: The aim of this study was to investigate differences of miRNA-34a expression in benign and malignant colorectal lesions. MATERIALS AND METHODS: Samples of cancer, paraneoplastic tissues and polyps were selected and total RNA was extracted by conventional methods for real-time PCR to detect the miRNA- 34a expression. In addition, the LOVO colorectal cancer cell line was cultured, treated with the demethylating agent 5-azacytidine and screened for differentially expressed miRNA-34a. RESULTS: After the drug treatment, the miRNA-34a expression of colorectal cancer cell line LOVO was increased and real-time PCR showed that levels of expression in both cell line and colorectal cancer tissues were low, as compared to paraneoplastic tissue (p<0.05). Polyps tissues had significantly higher expression than paraneoplastic and colorectal cancer samples (p<0.05). CONCLUSIONS: miRNA-34a-5p may play a role as a tumor suppressor gene in colorectal cancer, with involvement of DNA methylation.

Histogram analysis of apparent diffusion coefficient for the assessment of local aggressiveness of cervical cancer.

PURPOSE: To retrospectively explore the value of apparent diffusion coefficient (ADC) histogram in assessing local aggressiveness of cervical cancer. METHODS: 53 patients with cervical cancer, including 7 cases at stage IB1, 17 cases at stage IB2 and 29 cases at stage IIA, were subjected to preoperative MRI including diffusion-weighted imaging with b values of 0 and 800 s/mm(2). The average of mean ADC values (ADCmean), minimum ADC values (ADCmin) and the 5th to 85th percentile ADC values every 10 % (ADC5 %, ADC15 %, ADC85 %) were measured. ADC values were compared between subgroups according to pathologic subtype, histological differentiation, depth of cervical infiltration, and lymph node metastases. RESULTS: ADCmean and ADCmin for adenocarcinoma were 1,170.3 ± 97.8 × 10(-6) and 748.7 ± 157.5 × 10(-6) mm(2) s(-1), respectively, significantly higher than that of squamous cell carcinoma (SCC) (1,053.8 ± 134.3 × 10(-6) and 615.6 ± 170.2 × 10(-6) mm(2) s(-1), respectively). ADCmean and ADC5 %-ADC85 % of well or moderately tumor were significantly higher than poorly differentiated tumor, but ADCmin was not significantly different among different differentiated cervical cancer. Only ADC5 %-ADC45 % could discriminate well or moderately differentiated SCC from poorly differentiated SCC. ADC5 % for distinguishing well/moderately from poorly differentiated cervical cancer had a largest AUC (0.83). There was no statistical difference in ADC value for different depth of cervical infiltration or lymph node metastases. CONCLUSIONS: ADC values are helpful in assessing pathologic subtype and the differentiation of cervical cancer.

[Value of diffusion-weighted imaging in diagnosis of lymph node metastasis in patients with cervical cancer].

OBJECTIVE: To investigate the value of diffusion-weighted imaging (DWI) in the differentiation of metastatic lymph nodes from non-metastatic lymph nodes in cervical cancer. METHODS: In 65 patients who underwent lymph node dissection for cervical cancer, conventional MRI and DWI examinations were performed before surgery. Of the 1590 total dissected pelvic lymph nodes, 392 enlarged nodes with a short-axis diameter (S )of 5 mm or greater were included for further analysis. Each of the size-based criteria [i.e., S, long-axis diameter (L), and S/L ratio] and apparent diffusion coefficient(ADC)-based criteria (i.e., ADCmin, ADCmean, rADCmin, rADCmean) were compared between metastatic lymph nodes and non-metastatic lymph nodes. RESULTS: There were statistically significant differences between metastatic and non-metastatic lymph nodes in S, L, S/L ratio, ADCmin, ADCmean, rADCmin, and rADCmean (all P<0.0001). The Az of the ADCmin (0.956) was greater than that of the other ADC-based criteria and all size-based criteria. Using ADCmin=759.0×10(-6) mm(2)/s, the sensitivity and specificity for differentiating metastatic from non-metastatic lymph nodes were 95.2% and 92.1%, respectively. CONCLUSION: DWI, particularly ADCmin, is feasible for differentiating metastatic from non-metastatic pelvic lymph nodes in patients with cervical cancer.