Effects of extremely low frequency pulsed magnetic fields on diabetic nephropathy in streptozotocin-treated rats.

BACKGROUND: Extremely low frequency pulsed magnetic fields (ELFPMF) have been shown to induce Faraday currents and measurable effects on biological systems. A kind of very high frequency electromagnetic field was reported that it improved the symptoms of diabetic nephropathy (DN) which is a major complication of diabetes. However, few studies have examined the effects of ELFPMF DN at the present. The present study was designed to investigate the effects of ELFPMF on DN in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS: Adult male SD rats were randomly divided into three weight-matched groups: Control (non-diabetic rats without DN), DN + ELFPMF (diabetic rats with DN exposed to ELFPMF, 8 h/days, 6 weeks) and DN (diabetic rats with DN exposed to sham ELFPMF). Renal morphology was examined by light and electron microscopy, vascular endothelial growth factor (VEGF)-A and connective tissue growth factor (CTGF) were measured by enzyme linked immune sorbent assay. RESULTS: After 6 weeks' ELFPMF exposure, alterations of hyperglycemia and weight loss in STZ-treated rats with DN were not found, while both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive one was that ELFPMF exposure attenuated the pathological alterations in renal structure observed in STZ-treated rats with DN, which were demonstrated by slighter glomerular and tubule-interstitial lesions examined by light microscopy and slighter damage to glomerular basement membrane and podocyte foot processes examined by electron microscopy. And then, the negative one was that ELFPMF stimulation statistically significantly decreased renal expression of VEGF-A and statistically significantly increased renal expression of CTGF in diabetic rats with DN, which might partially aggravate the symptoms of DN. CONCLUSION: Both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive effect induced by ELFPMF might play a dominant role in the procession of DN in diabetic rats, and it is suggested that the positive effect should be derived from the correction of pathogenic diabetes-induced mediators.

Protective effect of berberine against myocardial ischemia reperfusion injury: role of Notch1/Hes1-PTEN/Akt signaling.

Berberine (BBR) confers cardioprotective effect against myocardial ischemia reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also reduces MI/RI. We hypothesize that BBR may protect against MI/RI by modulating Notch1/Hes1-Phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signaling. In this study, male Sprague-Dawley rats were exposed to BBR treatment (200 mg/kg/d) for 2 weeks and then subjected to MI/RI. BBR significantly improved cardiac function recovery and decreased myocardial apoptosis, infarct size, serum creatine kinase and lactate dehydrogenase levels. Furthermore, in cultured H9c2 cardiomyocytes, BBR (50 µmol/L) attenuated simulated ischemia/reperfusion-induced myocardial apoptosis. Both in vivo and in vitro study showed that BBR treatment up-regulates Notch1 intracellular domain, Hes1, Bcl-2 expression and p-Akt/Akt ratio, down-regulates Bax Caspase-3 and cleaved Caspase-3 expression. However, the anti-apoptotic effect conferred by BBR was blocked by Notch1 siRNA, Hes1 siRNA or LY294002 (the specific inhibitor of Akt signaling) in the cultured cardiomyocytes. In summary, our results demonstrate that BBR treatment attenuates MI/RI by modulating Notch1/Hes1-PTEN/Akt signaling.

Generalization Performance of Pure Accuracy and its Application in Selective Ensemble Learning.

The pure accuracy measure is used to eliminate random consistency from the accuracy measure. Biases to both majority and minority classes in the pure accuracy are lower than that in the accuracy measure. In this paper, we demonstrate that compared with the accuracy measure and F-measure, the pure accuracy measure is class distribution insensitive and discriminative for good classifiers. The advantages make the pure accuracy measure suitable for traditional classification. Further, we mainly focus on two points: exploring a tighter generalization bound on pure accuracy based learning paradigm and designing a learning algorithm based on the pure accuracy measure. Particularly, with the self-bounding property, we build an algorithm-independent generalization bound on the pure accuracy measure, which is tighter than the existing bound of an order O(1/√N) (N is the number of instances). The proposed bound is free from making a smoothness or convex assumption on the hypothesis functions. In addition, we design a learning algorithm optimizing the pure accuracy measure and use it in the selective ensemble learning setting. The experiments on sixteen benchmark data sets and four image data sets demonstrate that the proposed method statistically performs better than the other eight representative benchmark algorithms.

RSS-Bagging: Improving Generalization Through the Fisher Information of Training Data.

The bagging method has received much application and attention in recent years due to its good performance and simple framework. It has facilitated the advanced random forest method and accuracy-diversity ensemble theory. Bagging is an ensemble method based on simple random sampling (SRS) method with replacement. However, SRS is the most foundation sampling method in the field of statistics, where exists some other advanced sampling methods for probability density estimation. In imbalanced ensemble learning, down-sampling, over-sampling, and SMOTE methods have been proposed for generating base training set. However, these methods aim at changing the underlying distribution of data rather than simulating it better. The ranked set sampling (RSS) method uses auxiliary information to get more effective samples. The purpose of this article is to propose a bagging ensemble method based on RSS, which uses the ordering of objects related to the class to obtain more effective training sets. To explain its performance, we give a generalization bound of ensemble from the perspective of posterior probability estimation and Fisher information. On the basis of RSS sample having a higher Fisher information than SRS sample, the presented bound theoretically explains the better performance of RSS-Bagging. The experiments on 12 benchmark datasets demonstrate that RSS-Bagging statistically performs better than SRS-Bagging when the base classifiers are multinomial logistic regression (MLR) and support vector machine (SVM).

Effects of 180 mT static magnetic fields on diabetic wound healing in rats.

Diabetic wound (DW) problems are becoming a formidable clinical challenge due to the sharp increase in the diabetic population and the high incidence of DW. Static magnetic field (SMF) therapy, an inexpensive and accessible noninvasive method, has been proven to be effective on various tissue repairs. However, the issue of the therapeutic effect of SMF on DW healing has never been investigated. The objective of this study was to systematically evaluate the effect of a 180 mT moderate-intensity gradient SMF on DW healing in streptozotocin-induced diabetic rats. Forty-eight 3-month-old male Sprague-Dawley rats (32 diabetic and 16 non-diabetic rats) were assigned to three equal groups: normal wound, DW, and DW + SMF groups. An open circular wound with 1.5 cm diameter was created in the dorsum. The wound was covered with a dressing and the magnet was fixed on top of the dressing. On days 5, 12, and 19, four rats of each group were euthanized and gross wound area, histology and tensile strength were evaluated. The wound area determination suggested that SMF significantly increased the healing rate and reduced the gross healing time. This result was further confirmed by histological observations. The wound tensile strength, reflecting the amount and quality of collagen deposition, increased to a larger extent in the DW + SMF group on days 12 and 19 compared with the DW group. The results indicated that 180 mT SMF presented a beneficial effect on DW healing, and implied the clinical potential of SMF therapy in accelerating DW repair and releasing the psychological and physical burdens of diabetic patients.

Pulsed electromagnetic fields (PEMF) attenuate changes in vertebral bone mass, architecture and strength in ovariectomized mice.

Pulsed electromagnetic fields (PEMF) has been investigated as a noninvasive alternative method to prevent bone loss for postmenopausal osteoporosis (OP), and the bone tissue involved in these studies are usually long bones such as femur and tibia in OP patients or rat models. However, few studies have investigated the effects of PEMF on the vertebral bone in mice with OP. This study aimed to investigate whether PEMF preserve lumbar vertebral bone mass, microarchitecture and strength in ovariectomized (OVX) mouse model of OP and its associated mechanisms. Thirty 3-month-old female BALB/c mice were randomly divided into three groups (n=10): sham-operated control (Sham), ovariectomy (OVX), and ovariectomy with PEMF treatment (OVX+PEMF). The OVX+PEMF group was exposed to 15Hz, 1.6 mT PEMF for 8h/day, 7days/week. After 8weeks, the mice were sacrificed. The OVX+PEMF group showed lower body weight gain of mice induced by estrogen deficiency compared with OVX group. Biochemical analysis of serum demonstrated that serum bone formation markers including bone specific alkaline phosphatase (BALP), serum osteocalcin (OCN), osteoprotegerin (OPG) and N-terminal propeptide of type I procollagen (P1NP) were markedly higher in OVX+PEMF group compared with OVX group. Besides, serum bone resorption markers including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal crosslinked telopeptides of type I collagen (CTX-I) were markedly lower in OVX+PEMF group compared with OVX group. Biomechanical test observed that OVX+PEMF group showed higher compressive maximum load and stiffness of the lumbar vertebrae compared with OVX group. Micro-computed tomography (µCT) and histological analysis of lumbar vertebrae revealed that PEMF partially prevented OVX-induced decrease of trabecular bone mass and deterioration of trabecular bone microarchitecture in lumbar vertebrae. Real-time PCR showed that the canonical Wnt signaling pathway of the lumbar vertebrae, including Wnt3a, LRP5 and ß-catenin were markedly up-regulated in OVX+PEMF group compared with OVX group. Moreover, the mRNA expressions of RANKL and OPG were markedly up-regulated in OVX+PEMF group compared with OVX group, whereas no statistical difference in RANKL/OPG mRNA ratio was found between OVX+PEMF group and OVX group. Besides, our study also found that the RANK mRNA expression was down-regulated in OVX+PEMF group compared with OVX group. Taken together, we reported that long-term stimulation with PEMF treatment was able to alleviate lumbar vertebral OP in postmenopausal mice through a combination of increased bone formation and suppressed bone resorption related to regulating the skeletal gene expressions of Wnt3a/LRP5/ß-catenin and OPG/RANKL/RANK signaling pathways.

Effects of four kinds of electromagnetic fields (EMF) with different frequency spectrum bands on ovariectomized osteoporosis in mice.

Electromagnetic fields (EMF) was considered as a non-invasive modality for treatment of osteoporosis while the effects were diverse with EMF parameters in time domain. In present study, we extended analysis of EMF characteristics from time domain to frequency domain, aiming to investigate effects of four kinds of EMF (LP (1-100 Hz), BP (100-3,000 Hz), HP (3,000-50,000 Hz) and AP (1-50,000 Hz)) on ovariectomized (OVX) osteoporosis (OP) in mice. Forty-eight 3-month-old female BALB/c mice were equally assigned to Sham, OVX, OVX + LP, OVX + BP, OVX + HP and OVX + AP groups (n = 8). After 8-week exposure (3 h/day), LP and BP significantly increased serum bone formation markers and osteogenesis-related gene expressions compared with OVX. Bedsides, LP and BP also slightly increased bone resorption activity compared with OVX, evidenced by increased RANKL/OPG ratio. HP sharply decreased serum bone formation and resporption markers and osteogenesis and osteoclastogenesis related gene expressions compared with OVX. AP had accumulative effects of LP, BP and HP, which significantly increased bone formation and decreased bone resporption activity compared with OVX. As a result, LP, BP and HP exposure did not later deterioration of bone mass, microarchitecture and mechanical strength in OVX mice with OP. However, AP stimulation attenuated OVX-induced bone loss.

Space Structure and Clustering of Categorical Data.

Learning from categorical data plays a fundamental role in such areas as pattern recognition, machine learning, data mining, and knowledge discovery. To effectively discover the group structure inherent in a set of categorical objects, many categorical clustering algorithms have been developed in the literature, among which k -modes-type algorithms are very representative because of their good performance. Nevertheless, there is still much room for improving their clustering performance in comparison with the clustering algorithms for the numeric data. This may arise from the fact that the categorical data lack a clear space structure as that of the numeric data. To address this issue, we propose, in this paper, a novel data-representation scheme for the categorical data, which maps a set of categorical objects into a Euclidean space. Based on the data-representation scheme, a general framework for space structure based categorical clustering algorithms (SBC) is designed. This framework together with the applications of two kinds of dissimilarities leads two versions of the SBC-type algorithms. To verify the performance of the SBC-type algorithms, we employ as references four representative algorithms of the k -modes-type algorithms. Experiments show that the proposed SBC-type algorithms significantly outperform the k -modes-type algorithms.

FTY720 enhances osteogenic differentiation of bone marrow mesenchymal stem cells in ovariectomized rats.

Sphingosine-1-phosphate and its structural analog FTY720 (fingolimod) are important in the inhibition of osteoclast differentiation and bone resorption, however, it remains unknown whether they enhance osteogenic differentiation of the bone marrow mesenchymal stem cells (BM­MSCs). The present study investigated the effect of FTY720 on the osteogenic differentiation of BM­MSCs from the femurs of the ovariectomized (OVX) rats. Three different concentrations (1, 10 and 100 nM) of FTY720 were demonstrated to markedly upregulate mRNA expression levels of Runt­related transcription factor 2 (Runx2) and Sp7 transcription factor (Sp7) at 2 weeks, and alkaline phosphatase (ALP) at 3 weeks. The osteocalcin (OCN) expression was similar at weeks 2 and 3. The protein expression levels of Runx2, Sp7, OCN and ALP induced by three different concentrations of FTY720 were higher than those in the control groups at 3 weeks in the OVX and sham groups. The findings of the current study suggested a beneficial effect of FTY720 on bone formation in OVX rats, and provided a potential therapeutic method of FTY720 to prevent alveolar bone resorption in patients with post­menopausal osteoporosis.

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study.

INTRODUCTION: The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. METHODS AND ANALYSIS: This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. ETHICS AND DISSEMINATION: The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. TRIAL REGISTRATION NUMBER: NCT02088346 (12 March 2014).

The effects of pulsed electromagnetic field on the functions of osteoblasts on implant surfaces with different topographies.

The use of pulsed electromagnetic fields (PEMFs) is a promising approach to promote osteogenesis. However, few studies have reported the effects of this technique on the osseointegration of endosseous implants, especially with regard to different implant topographies. We focused on how the initial interaction between cells and the titanium surface is enhanced by a PEMF and the possible regulatory mechanisms in this study. Rat osteoblasts were cultured on three types of titanium surfaces (Flat, Micro and Nano) under PEMF stimulation or control conditions. Protein adsorption was significantly increased by the PEMF. The number of osteoblasts attached to the surfaces in the PEMF group was substantially greater than that in the control group after 1.5h incubation. PEMF stimulation oriented the osteoblasts perpendicular to the electromagnetic field lines and increased the number of microfilaments and pseudopodia formed by the osteoblasts. The cell proliferation on the implant surfaces was significantly promoted by the PEMF. Significantly increased extracellular matrix mineralization nodules were observed under PEMF stimulation. The expression of osteogenesis-related genes, including BMP-2, OCN, Col-1,ALP, Runx2 and OSX, were up-regulated on all the surfaces by PEMF stimulation. Our findings suggest that PEMFs enhance the osteoblast compatibility on titanium surfaces but to different extents with regard to implant surface topographies. The use of PEMFs might be a potential adjuvant treatment for improving the osseointegration process.

Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, ß-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis.

Pulsed electromagnetic fields improve bone microstructure and strength in ovariectomized rats through a Wnt/Lrp5/ß-catenin signaling-associated mechanism.

Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and ß-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/ß-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.

Therapeutic effects of 15 Hz pulsed electromagnetic field on diabetic peripheral neuropathy in streptozotocin-treated rats.

Although numerous clinical studies have reported that pulsed electromagnetic fields (PEMF) have a neuroprotective role in patients with diabetic peripheral neuropathy (DPN), the application of PEMF for clinic is still controversial. The present study was designed to investigate whether PEMF has therapeutic potential in relieving peripheral neuropathic symptoms in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were randomly divided into three weight-matched groups (eight in each group): the non-diabetic control group (Control), diabetes mellitus with 15 Hz PEMF exposure group (DM+PEMF) which were subjected to daily 8-h PEMF exposure for 7 weeks and diabetes mellitus with sham PEMF exposure group (DM). Signs and symptoms of DPN in STZ-treated rats were investigated by using behavioral assays. Meanwhile, ultrastructural examination and immunohistochemical study for vascular endothelial growth factor (VEGF) of sciatic nerve were also performed. During a 7-week experimental observation, we found that PEMF stimulation did not alter hyperglycemia and weight loss in STZ-treated rats with DPN. However, PEMF stimulation attenuated the development of the abnormalities observed in STZ-treated rats with DPN, which were demonstrated by increased hind paw withdrawal threshold to mechanical and thermal stimuli, slighter demyelination and axon enlargement and less VEGF immunostaining of sciatic nerve compared to those of the DM group. The current study demonstrates that treatment with PEMF might prevent the development of abnormalities observed in animal models for DPN. It is suggested that PEMF might have direct corrective effects on injured nerves and would be a potentially promising non-invasive therapeutic tool for the treatment of DPN.