MR Diffusional Kurtosis Imaging-Based Assessment of Brain Microstructural Changes in Patients with Moyamoya Disease before and after Revascularization.

BACKGROUND AND PURPOSE: Conventional imaging examinations are insufficient to accurately assess brain damage in patients with Moyamoya disease. Our aim was to observe brain microstructural changes in patients with Moyamoya disease by diffusional kurtosis imaging and provide support data for application of this technique in individualized assessment of disease severity and surgical outcome among patients with Moyamoya disease. MATERIALS AND METHODS: A total of 64 patients with Moyamoya disease and 15 healthy volunteers underwent diffusional kurtosis imaging, and a second scanning was offered to surgical patients 3-4 months after revascularization. The diffusional kurtosis imaging parameter maps were obtained for mean kurtosis, axial kurtosis, radial kurtosis, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. The parameter values were measured in sensory pathway-related regions for all subjects. Differences in diffusional kurtosis imaging parameters of these brain regions were examined for healthy volunteers, patients without acroparesthesia, and asymptomatic and symptomatic sides of patients with acroparesthesia. Changes in diffusional kurtosis imaging parameters of patients with Moyamoya disease before and after revascularization were compared. RESULTS: Compared with healthy volunteers, patients with Moyamoya disease showed decreased mean kurtosis, axial kurtosis, radial kurtosis, and fractional anisotropy in the corona radiata. Similarly, mean kurtosis, radial kurtosis, and fractional anisotropy decreased in the posterior limb of the internal capsule, whereas axial kurtosis decreased and radial kurtosis increased in the thalami of patients with Moyamoya disease compared with healthy volunteers. Compared with the asymptomatic contralateral hemisphere, the symptomatic group showed increased mean kurtosis in the contralateral primary somatosensory cortex, increased fractional anisotropy in the contralateral corona radiata and posterior limb of the internal capsule, and decreased axial kurtosis in the contralateral thalamus. Among patients with Moyamoya disease with acroparesthesia, mean kurtosis decreased in the primary somatosensory cortex on the operated side following revascularization. CONCLUSIONS: The diffusional kurtosis imaging technique is applicable to patients with Moyamoya disease for detecting brain microstructural changes in white and gray matter before and after revascularization; this feature is useful in the assessment of disease severity and surgical outcome.

A variant of HLA-DRB1*11, HLA-DRB1*11:143, discovered in a Chinese hematopoietic stem cell donor.

HLA-DRB1*11:143 has one nucleotide change from HLA-DRB1*11:01:01 where Aspartic Acid (70) is changed to Glycine.

MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1α feedback loop.

OBJECTIVE: MiR-183 acts as an oncomiR and is usually upregulated in hepatocellular cancer (HCC). This study aims to study the association between miR-183 dysregulation and multi-drug resistance (MDR). Also, how it is dysregulated in HCC cells was investigated. MATERIALS AND METHODS: The association between miR-183 and HIF-1α in HCC cell line BEL-7402 and the multidrug-resistant variant BEL-7402/5-fluorouracil (BEL-7402/5-FU) were studied using qRT-PCR and Western blot analysis. The mediators involved in feedback regulation between miR-183 and HIF-1α were further studied. Then, the effect of the miR-183-SOCS6 axis on IC50 of BEL-7402/5-FU cells to 5-FU were investigated by MTT assay. RESULTS: The expression of miR-183 and HIF-1α are positively correlated in BEL-7402 and BEL-7402/5-FU cells. IDH2 knockdown resulted in significantly increased HIF-1α expression in both BEL-7402 and BEL-7402/5-FU cells. Knockdown of SOCS6 had similar but stronger effect as miR-183 in promoting MRP2, P-gp, p-STAT3 and HIF-1α expression in BEL-7402 cells, while SOCS6 overexpression also showed similar but stronger effect as miR-183 inhibition in reducing MRP2, P-gp, p-STAT3 and HIF-1α levels in BEL-7402/5-FU cells. Both SOCS6 overexpression and miR-183 knockdown significantly increased the sensitivity of BEL-7402/5-FU cells to 5-FU. MiR-183 overexpression partly abrogated the effect of SOCS6 in enhancing 5-FU sensitivity. CONCLUSIONS: Both HIF-1α-miR-183-IDH2-HIF-1α and HIF-1α-miR-183-SOCS6-p-STAT3-HIF-1α feedback loops are involved in miR-183 upregulation in HCC cells. MiR-183 can modulate MDR of HCC cells at least partly through suppressing SOCS6.

A new HLA-A allele, HLA-A*11:120, sequenced in a Chinese hematopoietic stem cell donor.

HLA-A*11:120 has one nucleotide change from HLA-A*11:01:01:01 where 295 T(ACC) is changed to S(AGC).

Autologous peripheral blood stem cell transplantation to treat thromboangiitis obliterans: preliminary results.

OBJECTIVE: To investigate the efficiency of autologous peripheral blood stem cell transplantation (APBSCT) to treat severe the lower limbs ischemia caused by thromboangiitis obliterans (TAO). PATIENTS AND METHODS: From April 2007 to December 2014, a total of 64 patients with TAO (80 affected limbs) received APBSCT at our hospital. The treatment effect was evaluated by subjective indicators including pains and cold sensation of the affected limbs, combined with objective indicators including claudication distance, ankle brachial index (ABI), transcutaneous oxygen pressure (TcPO2) and skin temperature. RESULTS: Five patients (with 5 affected limbs) suffered from necrosis below the middle of the leg 4 weeks after transplantation and received amputation. For the remaining 59 patients (75 affected limbs), pain and cold sensation of the affected limbs were improved with varying extent 3 months after transplantation; there were statistically significant differences in pain score and cold sensation score of the affected limbs before and after APBSCT (p<0.05). Claudication distance, ABI, TcPO2 and skin temperature were also improved. Claudication distance increased from 85.69 m ± 43.48 m to 36.5 ± 9.88 mmHg, and the skin temperature of the lower limbs increased from 27.70 °C ± 0.53 °C to 33.49 °C ± 0.60 °C. All four indicators were considerably improved after APBSCT (p<0.05). Arteriography was performed for 75 affected limbs in 59 patients 6 months after transplantation and found that new collateral vessels were formed in the affected limbs. No patients were complicated by retinal hyperplasia, malignant tumors, myocardial infarction and cerebral infarction during the follow-up examinations; no patients underwent symptom aggravation during 9-48 month follow-up (average, 28.5 months). CONCLUSIONS: APBSCT is an easy, safe and reliable treatment for ischemia of lower limbs, especially for those with poor distal arterial outflow tract in the lower limbs that do not permit bridging.

HLA-B*35:168, a novel HLA allele identified in a Chinese platelet donor.

HLA-B*35:168 has one nucleotide change from HLA-B*35:01:01:01 where 20 P is changed to R.

Early evaluation of targeted therapy effectiveness in non-small cell lung cancer by dynamic contrast-enhanced CT

Purpose. To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). Methods. We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. Results. Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). Conclusion. DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness (AU)

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Early evaluation of targeted therapy effectiveness in non-small cell lung cancer by dynamic contrast-enhanced CT.

PURPOSE: To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). METHODS: We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. RESULTS: Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). CONCLUSION: DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness.

Nimotuzumab with cisplatin or fluorouracil on human esophageal squamous cell carcinoma EC1 cells.

OBJECTIVE: To investigate the effects of nimotuzumab (h-R3) with cisplatin (DDP) or fluorouracil (5-FU) on human esophageal squamous cell carcinoma (ESCC) EC1 cells. MATERIALS AND METHODS: The assignment included blank control, h-R3 alone, DDP alone, 5-FU alone, h-R3 combined with DDP, and h-R3 combined with 5-FU. The cell proliferation in each group was measured by MMT method 48 h post dose. The effect on the cell cycle was determined by flow cytometry, and the effect on cell apoptosis was determined by flow cytometry and TUNEL test 48 h post dose. RESULTS: The inhibitory effect of h-R3 on the proliferation of EC1 cells was weak. The maximum inhibition rate was 10.10 ± 0.58% 48 h post dose, and the difference in the inhibition rate between the h-R3 with chemotherapeutic agents and the chemotherapeutic agent alone was not statistically significant (p > 0.05). Flow cytometry demonstrated no obvious change in the EC1 cells after h-R3 treatment (p > 0.05). Flow cytometry and TUNEL test demonstrated that the difference in the apoptosis rate between h-R3 combined with chemotherapeutic agents and blank control was not statistically significant (p > 0.05). CONCLUSIONS: h-R3 had no significant effect on human ESCC EC1 cells in vitro, with or without the combination of chemotherapeutic agents.

Effect of solid boundaries on swimming dynamics of microorganisms in a viscoelastic fluid.

We numerically study the effect of solid boundaries on the swimming behavior of a motile microorganism in viscoelastic media. Understanding the swimmer-wall hydrodynamic interactions is crucial to elucidate the adhesion of bacterial cells to nearby substrates which is precursor to the formation of the microbial biofilms. The microorganism is simulated using a squirmer model that captures the major swimming mechanisms of potential, extensile, and contractile types of swimmers, while neglecting the biological complexities. A Giesekus constitutive equation is utilized to describe both viscoelasticity and shear-thinning behavior of the background fluid. We found that the viscoelasticity strongly affects the near-wall motion of a squirmer by generating an opposing polymeric torque which impedes the rotation of the swimmer away from the wall. In particular, the time a neutral squirmer spends at the close proximity of the wall is shown to increase with polymer relaxation time and reaches a maximum at Weissenberg number of unity. The shear-thinning effect is found to weaken the solvent stress and therefore, increases the swimmer-wall contact time. For a puller swimmer, the polymer stretching mainly occurs around its lateral sides, leading to reduced elastic resistance against its locomotion. The neutral and puller swimmers eventually escape the wall attraction effect due to a releasing force generated by the Newtonian viscous stress. In contrast, the pusher is found to be perpetually trapped near the wall as a result of the formation of a highly stretched region behind its body. It is shown that the shear-thinning property of the fluid weakens the wall-trapping effect for the pusher squirmer.

Differential expression of candidate genes for lignin biosynthesis under drought stress in maize leaves.

In order to provide information for the development of molecular selection markers for drought tolerance improvement, the methods of prometric analysis, quantitative real-time PCR and field evaluation were employed for the identification of the differential expression of candidate genes under drought stress in maize. At seventeen, twenty-four and forty-eight hours of polyethylene glycol-simulated drought stress at the seventh leaf stage, leaf samples were collected from two drought-tolerant inbred lines for prometric analysis by two-dimensional electrophoresis and peptide mass fingerprinting. Fifty-eight proteins out of more than 500 were found in response to drought stress. Three drought-induced spots 2506, 3507 and 4506 showed sequence similarity with cinnamyl alcohol dehydrogenase, cytochrome protein 96A8 and S-adenosyl-L-methionine synthase, respectively. The expression of two key enzymes to lignin biosynthesis was quantified by quantitative real-time PCR among three drought-tolerant and one drought-sensitive inbred lines under drought stress and well-watered control conditions. After a decrease at the beginning of drought stress, the expression of cinnamyl alcohol dehydrogenase and caffeate O-methyltransferase recovered at twenty-four hours of the drought stress in the three drought-tolerant lines, but not in the drought-sensitive lines. Leaf lignin content, anthesis-silking interval and grain weight per plant were investigated with six inbred lines of varying drought tolerance under drought stress and well-watered control. Drought tolerance coefficients of these three characters were calculated and the correlation coefficients among these drought tolerance coefficients were estimated. Significant difference in leaf lignin content was found among the inbred lines and in response to drought stress. Close correlations were observed between the drought tolerant coefficients for leaf lignin content and grain weight per plant, and between the drought tolerant coefficients for leaf lignin content and anthesis-silking interval. These results indicate that leaf lignin content is a useful index for evaluation of drought tolerance in maize. Molecular selection markers can be developed on the basis of differential expression of the candidate genes and applied to maize improvement for drought tolerance.

Multiple loci in silico mapping in inbred lines.

The in silico mapping (ISM) technique and its extension represent major advances for novel gene discovery in germplasm resources of inbred lines. However, the techniques suffer from a relatively high false-positive rate (FPR) and they do not consider the effect of linkage disequilibrium (LD) markers around the identified quantitative trait locus (QTL). In addition, it has not yet been established whether it is optimal to use absolute trait differences as the response variable. To address these problems, this article presents the multiple loci ISM (MLISM) approach, which uses all markers on the entire genome, along with a penalized maximum likelihood. The method proposed here was verified by a series of simulation experiments with a maize pedigree population of inbred lines of known ancestry. Results from the simulated studies show that the best response variable is the trait product. The MLISM FPR is substantially decreased and the proportion of the number of false QTL to the number of LD markers around the identified QTL is adequately reduced. The MLISM method, with the trait product as the response variable, is an improvement on the existing methods for novel QTL mapping in germplasm resources of inbred lines.