An analysis of the relationship between donor and recipient biomarkers and kidney graft function, dysfunction, and rejection.

BACKGROUND: The study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. METHOD: Twenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in serum and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. RESULT: Our analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (D7; OR 1.119, 95% CI 1.016-1.233, p = 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97-1, p < 0.001), and this was the best predictive value of the renal function on D7. CONCLUSIONS: Donor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF.

The changes of neuroactivity of Tui Na (Chinese massage) at Hegu acupoint on sensorimotor cortex in stroke patients with upper limb motor dysfunction: a fNIRS study.

BACKGROUND: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. METHODS: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. RESULT: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). CONCLUSION: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients.

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.

[Application prospect of conditional gene editing animals and viral vectors in experimental research of acupuncturology].

Conditional gene editing animals and viral vectors have been widely applied in the research fields of biology and medicine. Recently, they are also used as the effective approaches to reveal the underlying mechanism of acupuncture from the nervous system to the specific molecules. In order to further understand the application of conditional gene editing animals and viral vectors, in this article, we analyze their characteristics, advantages and recent development in the field of acupuncture research and discuss their potential roles and prospect in the future.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury: a resting-state functional MRI study.

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Double-target neural circuit-magnetic stimulation improves motor function in spinal cord injury by attenuating astrocyte activation.

Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1ß, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.

Study protocol of a randomized controlled trial for the synergizing effects of rTMS and Tui Na on upper limb motor function and cortical activity in ischemic stroke.

Upper limb motor dysfunction after stroke is a serious threat to the living quality of patients and their families. Recovery of upper limb motor function after stroke largely relies on the activation and remodeling of neural circuits. rTMS (repetitive transcranial magnetic stimulation) has been proved to promote the reconstruction of neural synapses and neural circuits. However, there are still a large number of patients who cannot fully recover and leave behind varying degrees of dysfunction. Considering the systemic pathology after stroke, in addition to focal brain injury, stroke can also cause extensive dysfunction of peripheral organs. The rehabilitation strategy for stroke should combine the treatment of primary brain lesions with the intervention of secondary systemic damage. The aim of this trial is to verify the efficacy of rTMS synergize with Tui Na (Chinese Massage) on upper limb motor function after ischemic stroke, and to explore the mechanism of activation and remodeling of sensorimotor neural circuits with functional near-infrared spectroscopy. Ninety patients will be randomly assigned to either rTMS + Tui Na + conventional rehabilitation group (the experimental group) or rTMS + conventional rehabilitation group (the control group) in 1:1 ratio. Intervention is conducted five sessions a week, with a total of twenty sessions. The primary outcome is Fugl-Meyer Assessment, and the secondary outcomes include Muscle Strength, Modified Ashworth Assessment, Modified Barthel Index Assessment, motor evoked potentials and functional near-infrared spectroscopy. There are four time points for the evaluation, including baseline, 2 weeks and 4 weeks after the start of treatment, and 4 weeks after the end of treatment. This study is a randomized controlled trial. This study was approved by Institutional Ethics Committee of Shanghai Third Rehabilitation Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (approval No. SH3RH-2021-EC-012) on December, 16th, 2021. The protocol was registered with Chinese Clinical Trial Registry (ChiCTR2200056266), on February 3th, 2022. Patient recruitment was initiated on February 10th, 2022, and the study will be continued until December 2023.

Sensory and autonomic innervation of the local tissues at traditional acupuncture point locations GB14, ST2 and ST6.

OBJECTIVE: To visualize and compare the sensory and autonomic innervation of the local tissues at the sites of different traditional acupuncture points in the rat forehead and face by histochemical examination. METHODS: GB14 (Yangbai), ST2 (Sibai) and ST6 (Jiache) were selected as the representative traditional acupuncture points in this study, and the local tissues at these sites were dissected in rats after perfusion followed by double or triple fluorescent histochemical staining. Here, calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT) were used to label the sensory, sympathetic and parasympathetic nerve fibers, respectively. RESULTS: The CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers were simultaneously demonstrated in the local tissues at GB14, ST2 and ST6. Although the three kinds of nerve fibers ran in parallel or intermingled with each other, by the analysis from the view of three-dimensional reconstruction, it was clear that each of them distributed in an independent pattern to their corresponding target tissues including the blood vessels, hair follicles, arrector pili and subcutaneous muscles, as well as sebaceous glands. CONCLUSION: Our study demonstrated the sensory and autonomic innervation of the local tissues at GB14, ST2 and ST6, providing neurochemical evidence indicating that the CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers form a neural network at these point locations that may respond to acupuncture stimulation.

Effects of paired associative magnetic stimulation between nerve root and cortex on motor function of lower limbs after spinal cord injury: study protocol for a randomized controlled trial.

Classic paired associative stimulation can improve synaptic plasticity, as demonstrated by animal experiments and human clinical trials in spinal cord injury patients. Paired associative magnetic stimulation (dual-target peripheral and central magnetic stimulation) has been shown to promote neurologic recovery after stroke. However, it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury. We hypothesize that the current caused by central and peripheral magnetic stimulation will converge at the synapse, which will promote synapse function and improve the motor function of the relevant muscles. Therefore, this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials, motor and sensory function of the lower limbs, functional health and activities of daily living, and depression in patients with spinal cord injury. We will recruit 110 thoracic spinal trauma patients treated in the Department of Spinal Cord Injury, China Rehabilitation Hospital and randomly assign them to experimental and control groups in a 1:1 ratio. The trial group (n = 55) will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment. The control group (n = 55) will be treated with sham stimulation and conventional rehabilitation treatment. Outcomes will be measured at four time points: baseline and 4, 12, and 24 weeks after the start of intervention (active or sham paired associative magnetic stimulation). The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up. Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function score, motor evoked potentials, sensory evoked potentials, modified Ashworth scale score, Maslach Burnout Inventory score, and Hamilton Depression Scale score over time. Motor evoked potential latency reflects corticospinal tract transmission time, while amplitude reflects recruitment ability; both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency. Adverse events will be recorded. Findings from this trial will help to indicate whether paired associative magnetic stimulation (1) promotes recovery of lower limb sensory and motor function, reduces spasticity, and improves quality of life; (2) promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity; and (3) improves rehabilitation outcome in patients with spinal cord injury. Recruitment for this trial began in April 2021 and is currently ongoing. It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University, China (approval No. YZ2020-018) on May 18, 2020. The study protocol was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044794) on March 27, 2021 (protocol version 1.0). This trial will be completed in April 2022.

[Hydrochemical Characteristics and Transformation Relationship of Surface Water and Groundwater in the Plain Area of Bortala River Basin, Xinjiang].

The geological conditions of the Bortala River basin are complex, and the transformation of surface water and groundwater is frequent. It is great significance to study the hydrochemical characteristics and transformation relationship of surface water and groundwater for the reasonable development and allocation of water resources in the basin. Based on 15 surface water samples and 39 groundwater samples collected in April and May 2021, the APCS/MLR model and the combination of stable hydrogen and oxygen isotopes with hydrochemistry were used in this study to analyze the hydrochemical types and the distribution characteristics of hydrogen and oxygen isotopes, the source contribution of chemical components, and the transformation relationship between surface water and groundwater. The results showed that the surface water was mainly HCO3·SO4-Ca type and HCO3-Ca type, and the groundwater was mainly HCO3·SO4-Ca·Na type, HCO3-Ca type, and HCO3·SO4-Ca type. The contribution rates of the dissolution-migration-enrichment factor, human activities factor, environment factor, and native geological factor to the chemical components were 28.8%, 17.7%, 12.0%, and 6.5%, respectively. Bortala River water D and 18O was enriched along the distance, and groundwater D and 18O in the north bank was generally more enriched than groundwater in the south bank as a whole. Under the control of geological conditions such as geological structure and hydrogeological conditions, the transformation of river water and groundwater was concentrated in the middle reaches of the Bortala River, which was generally manifested in both unconfined groundwater and spring overflow in the sides of the recharge river water, and the recharge proportion ranged from 1.0% to 70.9%.

Alexa Fluor 488-conjugated cholera toxin subunit B optimally labels neurons 3-7 days after injection into the rat gastrocnemius muscle.

Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve injuries. However, it is not always clear which tracer should be used to yield optimal results. In this study, we examined the use of Alexa Fluor 488-conjugated cholera toxin subunit B (AF488-CTB). This was injected into the gastrocnemius muscle of rats, and it was found that motor, sensory, and sympathetic neurons were labeled in the spinal ventral horn, dorsal root ganglia, and sympathetic chain, respectively. Similar results were obtained when we injected AF594-CTB into the tibialis anterior muscle. The morphology and number of neurons were evaluated at different time points following the AF488-CTB injection. It was found that labeled motor and sensory neurons could be observed 12 hours post-injection. The intensity was found to increase over time, and the morphology appeared clear and complete 3-7 days post-injection, with clearly distinguishable motor neuron axons and dendrites. However, 14 days after the injection, the quality of the images decreased and the neurons appeared blurred and incomplete. Nissl and immunohistochemical staining showed that the AF488-CTB-labeled neurons retained normal neurochemical and morphological features, and the surrounding microglia were also found to be unaltered. Overall, these results imply that the cholera toxin subunit B, whether unconjugated or conjugated with Alexa Fluor, is effective for retrograde tracing in muscular tissues and that it would also be suitable for evaluating the regeneration or degeneration of injured nerves.

Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction.

Following a spinal cord injury, there are usually a number of neural pathways that remain intact in the spinal cord. These residual nerve fibers are important, as they could be used to reconstruct the neural circuits that enable motor function. Our group previously designed a novel magnetic stimulation protocol, targeting the motor cortex and the spinal nerve roots, that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury. Here, we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury. Rats underwent surgery to clamp the spinal cord at T10; three days later, the rats were treated with repetitive magnetic stimulation (5 Hz, 25 pulses/train, 20 pulse trains) targeting the nerve roots at the L5-L6 vertebrae. The treatment was repeated five times a week over a period of three weeks. We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord. In addition, the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex. Overall, the results suggest that nerve root magnetic stimulation may be an effective, noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

Effects of cortical intermittent theta burst stimulation combined with precise root stimulation on motor function after spinal cord injury: a case series study.

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury. We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral (right only) cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots, five times a week. Bilateral resting motor evoked potential amplitude was increased, central motor conduction time on the side receiving cortical stimulation was significantly decreased, and lower extremity motor score, Berg balance score, spinal cord independence measure-III score, and 10 m-walking speed were all increased after treatment. Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment. These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.

Histochemistry of microinfarcts in the mouse brain after injection of fluorescent microspheres into the common carotid artery.

The mouse model of multiple cerebral infarctions, established by injecting fluorescent microspheres into the common carotid artery, is a recent development in animal models of cerebral ischemia. To investigate its effectiveness, mouse models of cerebral infarction were created by injecting fluorescent microspheres, 45-53 µm in diameter, into the common carotid artery. Six hours after modeling, fluorescent microspheres were observed directly through a fluorescence stereomicroscope, both on the brain surface and in brain sections. Changes in blood vessels, neurons and glial cells associated with microinfarcts were examined using fluorescence histochemistry and immunohistochemistry. The microspheres were distributed mainly in the cerebral cortex, striatum and hippocampus ipsilateral to the side of injection. Microinfarcts were found in the brain regions where the fluorescent microspheres were present. Here the lodged microspheres induced vascular and neuronal injury and the activation of astroglia and microglia. These histopathological changes indicate that this animal model of multiple cerebral infarctions effectively simulates the changes of various cell types observed in multifocal microinfarcts. This model is an effective, additional tool to study the pathogenesis of ischemic stroke and could be used to evaluate therapeutic interventions. This study was approved by the Animal Ethics Committee of the Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences (approval No. D2021-03-16-1) on March 16, 2021.

[Application of Adobe Illustrator for drawing schematic diagrams of anatomical structure of acupoints -- taking Five Shu-points of Jueyin Meridian as an example].

The schematic diagram is an indispensable part of research article in life science，which can effectively and intuitively show the specific content of the article with simple composition. As an intuitive expression of the interdisciplinary subject at the early stage, the schematic diagram in the literature has gained an all-round improvement in the quality along with the deve-lopment of computer technology and modern drawing tools. In contrast，the level of the schematic diagram appears to be lagged behind in the field of acupuncture research papers. In order to improve the drawing level of this field, we took the Five Shu-points of Hand and Foot Jueyin Meridian as an example, and drew some vector diagrams of their anatomical structures including the body surface, skeleton, nerves, arteries and veins by using the Adobe Illustrator image software, through which we sum up a simple and easy-to-learn process including application skills and key points needing attention. We hope these methods can play a role in the acupuncture research in the future.

LncRNA H19 Mitigates Oxidized Low-Density Lipoprotein Induced Pyroptosis via Caspase-1 in Raw 264.7 Cells.

Atherosclerosis (AS) is mainly characterized by the activation of inflammatory cells and chronic inflammatory responses after cell injury. Pyroptosis is a form of programmed cell death (PCD) accompanied by the release of inflammatory factors. Many studies have shown that pyroptosis plays an important role in AS. Increasing evidence also indicates that long non-coding RNA H19 (lncRNA H19) involved in AS. However, whether the role of lncRNA H19 in AS is related to pyroptosis and the underlying mechanisms are largely unknown. In this study, we found that oxidized low-density lipoprotein (ox-LDL) induced pyroptosis and decreased the expression of lncRNA H19 in Raw 264.7 cells. Besides, silencing endogenous lncRNA H19 increased inflammatory responses and pyroptosis while exogenous overexpression of lncRNA H19 reversed this effect. Notably, we identified that the inhibitor of caspase-1 (XV-765) completely abrogated the silencing endogenous lncRNA H19 mediated pyroptosis. In addition, we found that lncRNA H19 inhibited ox-LDL-induced activation of nuclear factor-kappa B (NF-κB), mitochondrial dysfunction, and reduced the production of reactive oxygen species (ROS). Moreover, VX-765 impaired the silencing endogenous lncRNA H19 mediated pyroptosis. Overall, these findings indicated that lncRNA H19 may play an important role in pyroptosis and may serve as a potential therapeutic target for AS.

Icariin attenuates endothelial-mesenchymal transition via H19/miR-148b-3p/ELF5 in ox-LDL-stimulated HUVECs.

Atherosclerosis is the main cause of cardio-cerebrovascular diseases. Endothelial-mesenchymal transition plays an important role in atherosclerosis. Icariin has a protective effect on atherosclerosis; however, the underlying mechanism remains unclear. In this study, we explored the molecular mechanism underlying the protective function of icariin in oxidized low-density lipoprotein-stimulated human umbilical vein endothelial cells. H19, a long non-coding RNA, was identified to be downregulated in the background of the oxidized low-density lipoprotein-induced endothelial-mesenchymal transition in human umbilical vein endothelial cells. Icariin upregulated H19 expression and inhibited the transformation of endothelial cells into interstitial cells. Overexpression of H19 affected endothelial-mesenchymal transition in oxidized low-density lipoprotein-stimulated human umbilical vein endothelial cells, whereas H19 knockdown reversed endothelial protective effects of icariin and reduced human umbilical vein endothelial cell migration. Knockdown of H19 significantly downregulated oxidized low-density lipoprotein-induced E74-like factor 5 and upregulated miR-148b-3p, which was reversed by icariin. Thus, icariin may play a protective role in atherosclerosis, and H19 may be a potential therapeutic target.

Using Hebbian-Type Stimulation to Rescue Arm Function After Stroke: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Upper-extremity hemiplegia after stroke remains a significant clinical problem. The supplementary motor area (SMA) is vital to the motor recovery outcomes of chronic stroke patients. Therefore, rebuilding the descending motor tract from the SMA to the paralyzed limb is a potential approach to restoring arm motor function after stroke. Paired associative stimulation (PAS), which is based on Hebbian theory, is a potential method for reconstructing the connections in the impaired motor neural circuits. The study described in this protocol aims to assess the effects of cortico-peripheral Hebbian-type stimulation (HTS), involving PAS, for neural circuit reconstruction to rescue the paralyzed arm after stroke. METHODS: The study is a 4-month double-blind randomized sham-controlled clinical trial. We will recruit 90 post-stroke individuals with mild to moderate upper limb paralysis. Based on a 1:1 ratio, the participants will be randomly assigned to the HTS and sham groups. Each participant will undergo 5-week HTS or sham stimulation. Assessments will be conducted at baseline, immediately after the 5-week treatment, and at a 3-month follow-up. The primary outcome will be the Wolf Motor Function Test (WMFT). The secondary outcomes will be Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Functional Independence Measure (FIM), and functional near-infrared spectroscopy (fNIRS) parameters. The adverse events will be recorded throughout the study. DISCUSSION: Upper-limb paralysis in stroke patients is due to neural circuit disruption, so the reconstruction of effective motor circuits is a promising treatment approach. Based on its anatomical structure and function, the SMA is thought to compensate for motor dysfunction after focal brain injury at the cortical level. Our well-designed randomized controlled trial will allow us to analyze the clinical efficacy of this novel Hebbian theory-based neuromodulation strategy regarding promoting the connection between the cortex and peripheral limb. The results may have significance for the development and implementation of effective neurorehabilitation treatments. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [ChiCTR2000039949].

Prospects for intelligent rehabilitation techniques to treat motor dysfunction.

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments. Therefore, new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation. Based on routine rehabilitation treatments, a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training. The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization, standardization, and intelligence. Traditional assessment methods are mostly subjective, depending on the experience and expertise of clinicians, and lack standardization and precision. It is therefore difficult to track functional changes during the rehabilitation process. Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment. Artificial intelligence and neural networks play a critical role in intelligent rehabilitation. Multiple novel techniques, such as brain-computer interfaces, virtual reality, neural circuit-magnetic stimulation, and robot-assisted therapy, have been widely used in the clinic. This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

Prospects for the application of transcranial magnetic stimulation in diabetic neuropathy.

Encouraging results have been reported for the use of transcranial magnetic stimulation-based nerve stimulation in studies of the mechanisms of neurological regulation, nerve injury repair, and nerve localization. However, to date, there are only a few reviews on the use of transcranial magnetic stimulation for diabetic neuropathy. Patients with diabetic neuropathy vary in disease progression and show neuropathy in the early stage of the disease with mild symptoms, making it difficult to screen and identify. In the later stage of the disease, irreversible neurological damage occurs, resulting in treatment difficulties. In this review, we summarize the current state of diabetic neuropathy research and the prospects for the application of transcranial magnetic stimulation in diabetic neuropathy. We review significant studies on the beneficial effects of transcranial magnetic stimulation in diabetic neuropathy treatment, based on the outcomes of its use to treat neurodegeneration, pain, blood flow change, autonomic nervous disorders, vascular endothelial injury, and depression. Collectively, the studies suggest that transcranial magnetic stimulation can produce excitatory/inhibitory stimulation of the cerebral cortex or local areas, promote the remodeling of the nervous system, and that it has good application prospects for the localization of the injury, neuroprotection, and the promotion of nerve regeneration. Therefore, transcranial magnetic stimulation is useful for the screening and early treatment of diabetic neuropathy. Transcranial magnetic stimulation can also alleviate pain symptoms by changing the cortical threshold and inhibiting the conduction of sensory information in the thalamo-spinal pathway, and therefore it has therapeutic potential for the treatment of pain and pain-related depressive symptoms in patients with diabetic neuropathy. Additionally, based on the effect of transcranial magnetic stimulation on local blood flow and its ability to change heart rate and urine protein content, transcranial magnetic stimulation has potential in the treatment of autonomic nerve dysfunction and vascular injury in diabetic neuropathy. Furthermore, oxidative stress and the inflammatory response are involved in the process of diabetic neuropathy, and transcranial magnetic stimulation can reduce oxidative damage. The pathological mechanisms of diabetic neuropathy should be further studied in combination with transcranial magnetic stimulation technology.