Towards Image Guided Magnetic Resonance Elastography via Active Driver Positioning Robot.

Magnetic Resonance Elastography (MRE) is a developing imaging technique that enables non-invasive estimation of tissue mechanical properties through the combination of induced mechanical displacements in the tissue and Magnetic Resonance Imaging (MRI). The mechanical drivers necessary to produce shear waves in the tissue have been a focus of engineering effort in the development and refinement of MRE. The potential targeting of smaller and stiffer tissues calls for increases in actuation frequency and refinement of mechanical driver positioning. Furthermore, the anisotropic nature of soft tissues results in driver position related changes in observed displacement wave patterns. These challenges motivate the investigation and development of the concept of active MRE driver positioning through visual servoing under MR imaging. OBJECTIVE: This work demonstrates the initial prototype of an MRE driver positioning system, allowing capture of displacement wave patterns from various mechanical vibration loading angles under different vibration frequencies through MR imaging. METHODS: Three different configurations of the MRE driver positioning robot are tested with an intervertebral disc (IVD) shaped gel phantom. RESULTS: Both the octahedral shear stress signal to noise ratio (OSS-SNR) and estimated stiffness show statistically significant dependence on driver configuration in each of the three phantom IVD regions. CONCLUSION: This dependence demonstrates that driver configuration is a critical factor in MRE, and that the developed robot is capable of producing a range of configurations. SIGNIFICANCE: This work presents the first demonstration of an active, imaging guided MRE driver positioning system, with significance for the future application of MRE to a wider range of human tissues.

Metallic-State MoS2 Nanosheets with Atomic Modification for Sodium Ion Batteries with a High Rate Capability and Long Lifespan.

Exploring active materials with a high rate capability and long lifespan for sodium ion batteries attracts much more attention and plays an important role in realizing clean energy storage and conversion. The strategy of optimizing the electronic structure by atomic element substitution within MoS2 layers was employed to change the inherent physical property. The enhanced electronic conductivity from a decreased bandgap and increased surface Na+ adsorption energy can efficiently and dramatically optimize the electrochemical performance for sodium storage. Attempting to limit the large volume variation and avoid MoS2 nanosheet stacking and restacking, numerous nanosheets are in situ grown into a designed hierarchical mesopore carbon matrix. This structure can tightly capture the nanosheets to prevent them from aggregating and offer a sufficient buffer zone for alleviating severe volume changes during the discharging/charging process, contributing remarkably to the structural integrity and superior rate performance of electrodes.

A Direct Drive Parallel Plane Piezoelectric Needle Positioning Robot for MRI Guided Intraspinal Injection.

Recent developments in the field of cellular therapeutics have indicated the potential of stem cell injections directly to the spinal cord. Injections require either open surgery or a Magnetic Resonance Imaging (MRI) guided injection. Needle positioning during MRI imaging is a significant hurdle to direct spinal injection, as the small target region and interlaminar space require high positioning accuracy. OBJECTIVE: To improve both the procedure time and positioning accuracy, an MRI guided robotic needle positioning system is developed. METHODS: The robot uses linear piezoelectric motors to directly drive a parallel plane positioning mechanism. Feedback is provided through MRI during the orientation procedure. Both accuracy and repeatability of the robot are characterized. RESULTS: This system is found to be capable of repeatability below 51 µm. Needle endpoint error is limited by imaging modality, but is validated to 156 µm. CONCLUSION: The reported robot and MRI image feedback system is capable of repeatable and accurate needle guide positioning. SIGNIFICANCE: This high accuracy will result in a significant improvement to the workflow of spinal injection procedures.

Serum uric acid is independently associated with diabetic nephropathy but not diabetic retinopathy in patients with type 2 diabetes mellitus.

BACKGROUND: This study aims to investigate the relationship between serum uric acid (SUA) and the severity of diabetic nephropathy (DN) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2961 patients were enrolled in the present cross-sectional study. The severity of DN was determined by 24-hour urinary albumin excretion (UAE), which was classified as normal (UAE <30 mg/24 h), microalbuminuria (UAE: 30-299 mg/24 h), and macroalbuminuria (≥300 mg/24 h). The severity of DR was determined by non-mydriatic retinal photography and was classified as non-diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative DR (PDR). RESULTS: Patients with high SUA levels (≥420 µmol/L for males and ≥360 µmol/L for females) had a significantly higher prevalence of DN (UAE ≥30 mg/24 h, 39.3% vs 26.3%; p < 0.001), higher UAE levels (140 ± 297 vs 63 ± 175 mg/24 h; p < 0.001), and lower estimated glomerular filtration rate (eGFR; 79.3 ± 26.8 vs 96.8 ± 19.6 mL/min/1.73 m; p < 0.001), when compared with patients with normal SUA levels. However, the prevalence of DR, NPDR, or PDR did not differ. Furthermore, the concentration of SUA was higher in patients with higher severity of DN (all, p < 0.001) and patients with PDR (compared with NDR or NPDR, p < 0.05). SUA levels were positively associated with male gender, body mass index, the use of diuretics, triglyceride, low-density lipoprotein, and UAE levels, whereas they were negatively correlated with high-density lipoprotein, fasting blood glucose, glycosylated hemoglobin, and eGFR. After adjustment, SUA remained significantly associated with UAE (r = 0.069, p < 0.001). CONCLUSION: For patients with T2DM, higher SUA levels are associated with higher UAE, lower eGFR, and higher prevalence of DN, but not DR.

[Clinical effect of Nd:YAG laser combined with total glucosides of paeony for the treatment of erosive oral lichen planus].

PURPOSE: To investigate the clinical effect of Nd:YAG laser combined with total glucosides of paeony (TGP) taken orally for the treatment of erosive oral lichen planus (OLP). METHODS: Sixty patients who were diagnosed as erosive OLP with clinical symptoms were divided into experimental group (n=28) and control group (n=32) using a random number table. All patients received TGP while the patients in the experimental group were given Nd:YAG laser irradiation. The clinical effects were evaluated 3 months after treatment. The data were analyzed using SPSS 17.0 software package. RESULTS: Three months later, the average VAS score and sign score had improved significantly to (1.36±1.39) and (2.32±1.56) in the experimental group. The same tendency was observed in the control group and at the time point no significant difference was observed between the experimental group and the control group. The effectiveness of the experimental group was significantly higher than the control group (82.1% vs 53.1%). CONCLUSIONS: Nd: YAG laser combined with TGP can improve the efficacy of erosive OLP. The regime is safe and effective, which is worth of wide clinical application.

Pharmacokinetics and safety of cyclophosphamide and docetaxel in a hemodialysis patient with early stage breast cancer: a case report.

BACKGROUND: Standardized chemotherapy used in cancer patients with severe kidney insufficiency is ineffective. Although there are some pharmacokinetic studies on cyclophosphamide in kidney insufficiency patients, to the best of our knowledge, the pharmacokinetics and safety of combination of cyclophosphamide and docetaxel as postoperative chemotherapy in a patient with early stage breast cancer undergoing hemodialysis is unclear thus far. CASE PRESENTATION: The patient received regular TC regimen (cyclophosphamide 600 mg/m2, docetaxel 75 mg/m2). She underwent hemodialysis 48 h after chemotherapy. Blood samples at multiple time-points were collected for determination of plasma levels of cyclophosphamide and docetaxel. Pharmacokinetic analyses indicated that compared with the reference data, the in vivo half-life (66.96 h) and drug exposure (150%) of cyclophosphamide significantly increased; however, pharmacokinetic parameters of docetaxel was unaffected. Patient developed grade I thrombocytopenia and grade III leukopenia without any other severe adverse reactions. In total, four cycles of treatment were completed. After the chemotherapy, the patient received tamoxifen as endocrine therapy for one and a half years. No recurrence was reported. CONCLUSION: These results suggest that the standard TC regimen is mostly safe and could be used as postoperative adjuvant chemotherapy for hemodialysis patients with early stage breast cancer.

MiR-454 prompts cell proliferation of human colorectal cancer cells by repressing CYLD expression.

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.

Combining bevacizumab and panitumumab with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as second-line treatment in patients with metastatic colorectal cancer.

Bevacizumab and panitumumab are human monoclonal antibodies with different targeting antigens, vascular endothelial growth factor, and epidermal growth factor receptor. This study examined the efficacy and safety of combining bevacizumab and panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer (mCRC). Patients with mCRC, and previously failed with oxaliplatin-based chemotherapy, were given bevacizumab (3 mg/kg) and panitumumab (3 mg/kg) plus FOLFIRI every other week. From September 2008 to July 2012, 173 patients were included in the study. The response rate was 42.3 %, and the disease-controlled rate was 65.7 %. The median progression-free survival was 6.5 months, and the median overall survival was 15.4 months. Various adverse events (AE) including those known toxicities associated with antibody therapy were recorded. The overall AE rate was 64.5 % for grade 3-4. The treatment of combining bevacizumab and panitumumab plus FOLFIRI is effective and safe as a second-line therapy for patients with mCRC.

Resveratrol attenuates renal hypertrophy in early-stage diabetes by activating AMPK.

BACKGROUND: Recent studies suggest the involvement of the adenosine monophosphate-activated serine/threonine protein kinase (AMPK) pathway in the pathogenesis of diabetic nephropathy (DN). Resveratrol, an agent that activates AMPK, may have the potential to protect against the development of DN. This study was designed to investigate the therapeutic effects of resveratrol on renal hypertrophy in early-stage diabetes and the underlying mechanisms. METHOD: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of early-stage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring (3)H-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phospho- ribosomal protein S6 (S6) was analyzed by Western blot. RESULTS: Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs. CONCLUSION: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN.

[Effects of lactose inducing on expression of Helicobacter pylori rUreB and rHpaA, and Escherichia coli rLTKA63 and rLTB].

OBJECTIVE: To determine the effects of lactose inducing on the expression of recombinant Helicobacter pylori rUreB and rhpaA, and Escherichia coli rLTB and rLTKA63. METHODS: BIO-RAD gel image analysis system was applied to detect the outputs of the recombinant proteins. SDS-PAGE was performed to measure the target protein expression of recombinant genes at various periods of growth, different lactose concentrations, various inducing temperatures and times. The results of the target protein expression induced by lactose were compared to those by isopropyl-beta-D-thiogalactoside (IPTG). RESULTS: Lactose showed higher efficiency to induce the expression of rHpaA, rUreB, rLTB and rLTKA63 than IPTG. The expression outputs of target recombinant proteins induced at 37 degrees C were remarkably higher than those at 28 degrees C. The optimal expression parameters were 0.8 of OD600 value, 50 g/L of lactose, 4 hours of inducing time for rHpaA, and 1.2 of OD600 value, 100 g/L of lactose, 5 hours of inducing time for both the rUreB and rLtB,and 0.8 of OD600 value, 100 g/L of lactose, 4 hours for rLTKA63. CONCLUSION: Lactose, a sugar with non-toxicity and low cost, is able to induce the recombinant genes to express the target proteins with higher efficiency than IPTG.

[Studies on IR fingerprint of tongren dahuoluo pills and tongren niuhuangqingxin pills].

OBJECTIVE: To identify Tongren Dahuoluo pills and Tongren Niuhuangqingxin pills respectively by analysis of IR fingerprint. METHOD: Both drugs were extracted with hexane, ethylether and butanone respectively and then the obtained extracts were measured with the ET-IR spectrometer. RESULT: By analyzing IR fingerprint of 25 batches of Tongren Dahuoluo pills and 27 batches of Tongren Niuhuangqingxin pills, we found that different batches of the same drug hadstabile and repeatable fingerprint. CONCLUSION: By using IR fingerprint, either Tongren Dahuoluo pills or Tongren Niuhuangqingxin pills can be exactly identified. It provides a rapid method for drug identification and quality control.

[Naloxone for attenuation of interleukin 2 induced myocardial depression in rat hearts].

OBJECTIVE: To investigate the cardiac effect of interleukin-2 (IL-2) and to explore the underlying mechanism. METHODS: The video tracking system and spectrofluorometric method were used to measure the cell contraction and intracellular calcium. Fura-2/AM was used as a calcium fluorescence probe. Langendorff perfusion technique was used to determine the effect of IL-2 on the intact heart. RESULTS: Compared with the control group, IL-2 5 U/ml, 50 U/ml significantly decreased cell contraction amplitude [(74.95+/-4.79) vs (98.09+/-5.02)%, (64.30+/-5.24) vs (97.38+/-4.05)%], peak velocity of cell shortening [(70.23+/-4.85)% vs (98.09+/-5.46)%, (61.15+/-5.20)% vs (97.38+/-6.85)%], peak velocity of cell relengthening [(71.22+/-4.79)% vs (98.32+/-6.08)%, (68.16+/-5.24)% vs (97.55+/-5.00)%] and end- diastolic cell length [(88.28+/-5.84)% vs (97.95+/-5.52)%, (84.18+/-6.52)% vs (98.94+/-6.76)%]. IL-2 (5 U/ml, 50 U/ml) also markedly inhibited intracellular calcium transient [(74.94+/-4.90)% vs (98.09+/-3.74)%,(71.00+/-5.28)% vs (97.38+/-5.52)%], and elevated end-diastolic calcium level of ventricular myocytes [(113.91+/-5.93)% vs (100.10+/-3.02)%, (119.09+/-7.12)% vs (100.52+/-6.00)%], which were attenuated by the opioid receptor antagonist naloxone (Nal,10 nmol/L). In the isolated perfused rat heart,when compared with the control group, IL-2 50 U/ml markedly decreased left ventricular developed pressure [(79.91+/-2.18) vs (93.84+/-2.94)mmHg], maximal rate of rise of left ventricular pressure [(2370.7358.29) vs (2591.50+/-62.81)mmHg] maximal rate of fall of left ventricular [-(1460.95+/-38.6) vs -(1634.24+/-54.05) mmHg/s] and heart rate [(217.35+/-10.56) vs (244.52+/-11.23) beats/min], but increased left ventricular end-diastolic pressure (11.44+/-1.02 vs 9.23+/-0.46). Pretreatment with Nal (10 nmol/L) antagonized the cardiac depression and left ventricular end-diastolic pressure elevation induced by IL-2. CONCLUSION: The cardiac effect of IL-2 is mediated by opioid receptors on the membrane of cardiomyocytes.

[Establishment of Helicobacter pylori infection model in Mongolian gerbil].

OBJECTIVE: To establish a stable and reliable model of Helicobacter pylori infection in Mongolian gerbil and to observe pathological changes in gastric mucosa from the infected animals. METHODS: Mongolian gerbils were randomly divided into six groups infected with H.pylori strain NCTC11637 (n=6, group N), six groups infected with H.pylori clinical strain Y06 (n=6, group Y) and six groups as negative control (n=4, group C). H.pylori suspensions at the concentrations of 2 X 10(8)CFU/ml and 2 X 10(9) CFU/ml of strain NCTC11637 and strain Y06 were prepared with Brucella broth from Columbia agar containing sheet blood. The animals in one group N and in one group Y were orally challenged once with 0.5 ml of 2 X 10(8) CFU/ml H.pylori suspension. The animals in another group N and in another group Y were orally challenged with 0.5 ml of 2 X 10(9) CFU/ml H.pylori suspension for three times at the intervals of 24 hours, respectively. The animals were killed after 2nd, 4th and 6th week of the last infection and the gastric mucosal samples were taken for urease test, bacterial isolation, routine pathological and H.pylori histochemical examinations. RESULTS: Infection rates of the animals in group N and group Y at the 2nd, 4th and 6th week after one challenge were 0%, 0%, 66.7% and 0%, 16.7%, 16.7%, respectively. Infection rates of the animals in groups N and Y at the 2nd, 4th and 6th week after three challenges were 66.7%, 100%, 100% and 66.7%, 66.7%, 100%, respectively. In animals with positive bacterial isolation H.pylori was found to colonized on the surface of gastric mucosal cells and in the gastric pits, and the lamina propria of gastric mucosal was infiltrated with chronic inflammatory cells. CONCLUSION: By using H.pylori suspension at high concentration of 1 X 10(9) CFU for multiple times, the orally challenged Mongolian gerbils can be prepared as a stable and reliable H.pylori infection model. H.pylori can colonize in gastric mucosa of the infected animals, and mild inflammation reactions can be seen.