Nano-based drug delivery systems for active ingredients from traditional Chinese medicine: Harnessing the power of nanotechnology.

Introduction: Traditional Chinese medicine (TCM) is gaining worldwide popularity as a complementary and alternative medicine. The isolation and characterization of active ingredients from TCM has become optional strategies for drug development. In order to overcome the inherent limitations of these natural products such as poor water solubility and low bioavailability, the combination of nanotechnology with TCM has been explored. Taking advantage of the benefits offered by the nanoscale, various drug delivery systems have been designed to enhance the efficacy of TCM in the treatment and prevention of diseases. Methods: The manuscript aims to present years of research dedicated to the application of nanotechnology in the field of TCM. Results: The manuscript discusses the formulation, characteristics and therapeutic effects of nano-TCM. Additionally, the formation of carrier-free nanomedicines through self-assembly between active ingredients of TCM is summarized. Finally, the paper discusses the safety behind the application of nano-TCM and proposes potential research directions. Discussion: Despite some achievements, the safety of nano-TCM still need special attention. Furthermore, exploring the substance basis of TCM formulas from the perspective of nanotechnology may provide direction for elucidating the scientific intension of TCM formulas.

H2S Alleviates Neuropathic Pain in Mice by Nrf2 Signaling Pathway Activation.

Neuropathic pain is a chronic pain caused by direct damage to the peripheral or central nervous system, characterized by hyperalgesia, allodynia, and spontaneous pain. Hydrogen sulfide (H2S) therapy has been applied for neuropathic pain treatment, although the underlying mechanisms remain unknown. In this study, we sought to ascertain whether H2S therapy could alleviate neuropathic pain in a model of chronic constriction injury (CCI) and, if so, the potential mechanism. A CCI model was established in mice through a spinal nerve ligation method. Intrathecal injection of NaHS was used to treat CCI model mice. The thermal paw withdrawal latency (TPWL) and mechanical paw withdrawal threshold (MPWT) were used for pain threshold evaluation in mice. A series of experiments including immunofluorescence, enzyme-linked immunosorbent assay, electrophysiological test, mitochondrial DNA (mtDNA) quantification, measurement of ATP content, demethylase activity, and western blot were performed to investigate the specific mechanism of H2S treatment in neuropathic pain. Mice with CCI exposure exhibited a decrease in MPWT and TPWL, an increase in IL-1ß and TNF-α expressions, elevated eEPSP amplitude, an upregulation of mtDNA, and a reduction in ATP production, whereas H2S treatment significantly reversed these changes. Furthermore, CCI exposure induced a remarkable increase in vGlut2- and c-fos-positive as well as vGlut2- and Nrf2-positive cells, an increase in Nrf2 located in the nucleus, and an upregulation of H3K4 methylation, and H2S treatment further enhanced these changes. In addition, ML385, a selective Nrf2 inhibitor, reversed the neuroprotective effects of H2S. H2S treatment mitigates CCI-induced neuropathic pain in mice. This protective mechanism is possibly linked to the activation of the Nrf2 signaling pathway in vGlut2-positive cells.

[Corrigendum] NEP1­40 promotes myelin regeneration via upregulation of GAP­43 and MAP­2 expression after focal cerebral ischemia in rats.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in Fig. 4A on p. 6 showing the effects of NEP1­40 on MBP expression as determined via immunohistochemical analysis, certain of the data panels appeared to be overlapping, such that they may have been derived from the same original source. After having examined their original data, the authors have realized that these data panels were inadvertently assembled incorrectly. A corrected version of Fig. 4 is shown below, incorporating data from one of the alternative experiments in Fig. 4A. Note that these errors did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 844, 2021; DOI: 10.3892/mmr.2021.12484].

Antioxidant Activities of Natural Polysaccharides and Their Derivatives for Biomedical and Medicinal Applications.

Many chronic diseases such as Alzheimer's disease, diabetes, and cardiovascular diseases are closely related to in vivo oxidative stress caused by excessive reactive oxygen species (ROS). Natural polysaccharides, as a kind of biomacromolecule with good biocompatibility, have been widely used in biomedical and medicinal applications due to their superior antioxidant properties. In this review, scientometric analysis of the highly cited papers in the Web of Science (WOS) database finds that antioxidant activity is the most widely studied and popular among pharmacological effects of natural polysaccharides. The antioxidant mechanisms of natural polysaccharides mainly contain the regulation of signal transduction pathways, the activation of enzymes, and the scavenging of free radicals. We continuously discuss the antioxidant activities of natural polysaccharides and their derivatives. At the same time, we summarize their applications in the field of pharmaceutics/drug delivery, tissue engineering, and antimicrobial food additives/packaging materials. Overall, this review provides up-to-date information for the further development and application of natural polysaccharides with antioxidant activities.

A Review of Non-Invasive Drug Delivery through Respiratory Routes.

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson's disease, Alzheimer's disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

The Shh/Gli1 signaling pathway regulates regeneration via transcription factor Olig1 expression after focal cerebral ischemia in rats.

OBJECTIVE: Ischemic stroke is a major cause of death in the global population, with a high disability and mortality rate. Lack of regenerative ability is considered to be the fundamental cause. This study aims to determine the effect of Shh pathway, which mediates regenerative signaling in response to CNS injury, on myelin repair and Olig1 expression in focal ischemic lesions in the rat. METHODS: A model of middle cerebral artery occlusion (MCAO) was established using the intraluminal suture method where the middle cerebral artery (MCA) was restricted for 120 min. Cyclopamine, a specific inhibitor of Shh, or saline was administered 12h after MCAO surgery and lasted for 7d. After MCA occlusion, male Sprague-Dawley rats were randomly allocated to cyclopamine- or saline-treated groups. A group of no-injection animals after MCAO were used as control. The Shh signaling pathway, myelinogenesis-related factor MBP and Olig1 were tested using immunohistochemistry and RT-PCR assay. RESULTS: The levels of Shh and its component Gli1 were elevated from 1d up to 14d following ischemia, indicating that the Shh-Gli1 axis was broadly reactivated. Treatment with cyclopamine can partially block the Shh signaling pathway, prevent myelin repair, and decrease the Olig1 expression following ischemic stroke. CONCLUSION: That blockade of Shh signaling concurrently with the creation of a lesion aggravated ischemic myelin damage, probably via its downstream effects on Olig1 transcription. Shh plays a contributory role during regeneration in the CNS, thereby providing promising new therapeutic strategies to assist in recovery from ischemic stroke.

Association Between Z Drugs Use and Risk of Cognitive Impairment in Middle-Aged and Older Patients With Chronic Insomnia.

Background: Benzodiazepines (BZDs) and Non-BZDs (NBZDs) have been widely used for patients with chronic insomnia. Long-term uses of BZDs may cause cognitive impairment and increase the risk for dementia in older patients. NBZD as an agonist of the GABAA receptor complex includes eszopiclone, zopiclone, zolpidem, and zaleplon, also collectively known as Z drugs. However, evaluations for an association between cognitive impairment and Z drug use have been limitedly performed. This study aimed to investigate the association between the risk of cognitive decline and exposure to Z drugs in middle-aged and older patients with chronic insomnia. Methods: Investigations were performed on patients with chronic insomnia who visited the outpatient Department of Neurology, Beijing Friendship Hospital, and were assessed for the global cognitive function (MoCA) and memory (AVLT), executive function (TMT-B), visuospatial ability (CDT), verbal function (BNT-30), and attention (DST). Multiple regression analysis was conducted to determine the independent factors of cognition and evaluated the effect of Z drug use (zolpidem and zopiclone) on cognition. Results: A total of 120 subjects were identified. In our analysis, BZD exposure density (P = 0.025, OR = 1.43, 95% CI, 1.25-1.86) was an independent risk factor of cognitive impairment in middle-aged and older patients with chronic insomnia. Neither Z drug use (P = 0.103) nor Z drug exposure density (P = 0.765) correlated with global cognitive function. Moreover, there was a positive association between Z drug use and attention [(P = 0.002, OR = 0.42, 95% CI, 0.24-0.73)]. Additionally, income level (P = 0.001, OR = 0.23, 95% CI, 0.10-0.53), severity of insomnia (P = 0.019, OR = 1.20, 95% CI, 1.03-1.40) and age (P = 0.044, OR = 1.07, 95% CI, 1.00-1.14) were also independent factors of global cognitive function. Conclusion: BZD exposure density was an independent risk factor of cognitive impairment in middle-aged and older patients with chronic insomnia, but no correlation was found between Z drug use and cognitive impairment. Moreover, the use of Z drugs seemed to be associated with protection for attention. The use for prescription of BZDs, in this case, should be avoided or limited to low doses. Due to the addiction and tolerance, Z drugs should also be prescribed with great caution in middle-aged and elderly patients.

NEP1­40 promotes myelin regeneration via upregulation of GAP­43 and MAP­2 expression after focal cerebral ischemia in rats.

Axon regeneration after lesions to the central nervous system (CNS) is largely limited by the presence of growth inhibitory molecules expressed in myelin. Nogo­A is a principal inhibitor of neurite outgrowth, and blocking the activity of Nogo­A can induce axonal sprouting and functional recovery. However, there are limited data on the expression of Nogo­A after CNS lesions, and the mechanism underlying its influences on myelin growth remains unknown. The aim of the present study was to observe the time course of Nogo­A after cerebral ischemia/reperfusion in rats using immunohistochemistry and western blot techniques, and to test the effect of its inhibitor Nogo extracellular peptide 1­40 (NEP1­40) on neural plasticity proteins, growth­associated binding protein 43 (GAP­43) and microtubule associated protein 2 (MAP­2), as a possible mechanism underlying myelin suppression. A classic model of middle cerebral artery occlusion (MCAO) was established in Sprague­Dawley rats, which were divided into three groups: i) MCAO model group; ii) MCAO + saline group; and iii) MCAO + NEP1­40 group. Rats of each group were divided into five subgroups by time points as follows: days 1, 3, 7, 14 and 28. Animals that only received sham operation were used as controls. The Nogo­A immunoreactivity was located primarily in the cytoplasm of oligodendrocytes. The number of Nogo­A immunoreactive cells significantly increased from day 1 to day 3 after MCAO, nearly returning to the control level at day 7, increased again at day 14 and decreased at day 28. Myelin basic protein (MBP) immunoreactivity in the ipsilateral striatum gradually decreased from day 1 to day 28 after ischemia, indicating myelin loss appeared at early time points and continuously advanced during ischemia. Then, intracerebroventricular infusion of NEP1­40, which is a Nogo­66 receptor antagonist peptide, was administered at days 1, 3 and 14 after MCAO. It was observed that GAP­43 considerably increased from day 1 to day 7 and then decreased to a baseline level at day 28 compared with the control. MAP­2 expression across days 1­28 significantly decreased after MCAO. Administration of NEP1­40 attenuated the reduction of MBP, and upregulated GAP­43 and MAP­2 expression at the corresponding time points after MCAO compared with the MCAO + saline group. The present results indicated that NEP1­40 ameliorated myelin damage and promoted regeneration by upregulating the expression of GAP­43 and MAP­2 related to neuronal and axonal plasticity, which may aid with the identification of a novel molecular mechanism of restriction in CNS regeneration mediated by Nogo­A after ischemia in rats.

[Optimization Method and Case Study of Air Pollution Emission Spatial Pattern].

Few of the current methods of improving air quality, including end-pipe treatment, industrial, energy and transportation structure adjustments, are from the viewpoint of the spatial pattern optimization of pollutant emissions. Therefore, based on factors such as natural environment, human health, pollutant transmission capability, and meteorological diffusion conditions, our research group used the threshold approach, natural breaks, spatial erasure, and other methods to define the layout area suitable for atmospheric pollution sources. Based on these results, the emissions pattern was optimized to achieve air quality improvement. Taking Guangdong Province as an example, we examined the application of the emissions pattern optimization of air quality improvement and atmospheric environment zoning. The results indicate that the first class area of environmental air quality accounts for 9% of total province area, the densely populated area accounts for 3%, the sensitive area of the national air quality monitor stations accounts for 15%, the pollutant accumulation area accounts for 22%, and the layout area suitable for atmospheric pollution sources primarily distributed in the west part of the province accounts for 60%. By shifting the non-thermal power industrial sources into those area, the concentration level of PM2.5 will decrease by 4% at the provincial scale and 10% at the city scale. Emissions pattern optimization has become an innovative aided support technology for the continuous improvement of air quality. In practical applications, it can be combined with energy and industrial structure adjustments, pollution control technology enhancements, and cross-regional prevention and control to formulate the most feasible air quality improvement plan.

Effects of the transcription factor Olig1 on the differentiation and remyelination of oligodendrocyte precursor cells after focal cerebral ischemia in rats.

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is important for remyelination in the central nervous system. Nevertheless, this process is often limited and incomplete in ischemic injury. Oligodendrocyte transcription factor 1 (Olig1) is important for the maturation of OPCs and the repair of demyelinated lesions. However, how Olig1 modulates the development of OPCs or the remyelination associated with ischemic injury remains unclear. The present study aimed to examine alterations in OPCs, and the expression of myelin and Olig1, at different time-points after focal cerebral ischemia using immunohistochemistry and western blot techniques to elucidate the role of Olig1 in the maturation of OPCs and remyelination. The present results showed that the expression of Olig1 significantly decreased at 1 day after middle cerebral artery occlusion (MCAO) and returned to normal levels from day 3 to 28. Additionally, Olig1 was found to translocate into the nucleus following ischemia in the brain. The number of OPCs in the ischemic striatum significantly declined at days 1 and 3 following MCAO, and increased at days 7, 14 and 28 compared with the control. The expression of myelin basic protein, a marker of mature oligodendrocytes and myelin, gradually decreased from day 1 to 7 after ischemia and recovered at day 14 and 28; however, the levels were lower than those in the control group. The present results indicated that the restored normal level of Olig1 following ischemia may play an important role in the maturation of OPCs through its translocation into the nucleus, where it may promote the growth and development of myelin under pathological conditions. However, this endogenous recovery mechanism fails to fully repair the demyelinated lesion. The data of the present study may help clinicians understand the expression pattern of Olig1 and its potential role in endogenous remyelination after ischemia, which may have implications for the treatment of diseases that lead to demyelination.

Clinical features and prognosis of patients with Guillain-Barré and acute transverse myelitis overlap syndrome.

OBJECTIVES: Patients who present with Guillain-Barré syndrome (GBS) and acute transverse myelitis (ATM), either simultaneously or consecutively, are defined as having GBS/ATM overlap syndrome. As this syndrome has been underinvestigated, we performed a literature review to evaluate case reports of GBS/ATM overlap syndrome to facilitate its early diagnosis. PATIENTS AND METHODS: We searched four scientific literature databases (PUBMED, EMBASE, ELSEVIER and WEB OF SCIENCE) for cases that presented as GBS/ATM overlap syndrome. Eighteen articles that described 23 cases were included, and the clinical and prognostic data were analyzed. RESULTS: Initially, only five (29.4%) patients were diagnosed with GBS/ATM overlap syndrome. Patients with GBS/ATM overlap syndrome presented as four clinical features. First, some of the patients displayed abnormal pyramidal signs, including 29.4% of patients who had positive pyramidal signs or a negative plantar reflex and 17.6% of patients who had signs of areflexia or hyporeflexia combined with positive pyramidal signs. Second, patients suffered pain and respiratory failure at a high rate (43.5% with pain at the onset of the disease, 43.5% with ventilator support, and 47.8% shown with respiratory failure). Third, patients had a partial clinical recovery of immunomodulators, 56.5% of patients had a favorable outcome, 46.2% of patients who received intravenous immunoglobulin (IVIG) combined steroids responded well to the treatment. Four, acute axonal polyneuropathy seemed to be associated with poor outcomes (odds ratio = 3.00, 95% CI = 1.35-6.68, P = 0.01). Abnormalities in spinal cord magnetic resonance imaging (MRI) were detected in all patients, and the most frequently involved segments were the cervical cord (69.6%) and the thoracic cord (69.6%). In addition to spinal cord lesions, in three patients lesions in the medulla and cerebral hemisphere were also observed. The most common prescriptions included a high dose of methylprednisolone at 1 g/day for 3-5 days that was followed by a 6-week course of oral prednisone and IVIG at 0.4 g/kg/day for 5 days. CONCLUSION: While it is difficult to make an early diagnosis of GBS/ATM overlap syndrome, electrophysiology is helpful in the diagnosis of GBS and spinal cord MRIs are key to identifying ATM. Brain MRIs are also recommended to detect subclinical lesions. The combined use of IVIG and steroids was the most frequent treatment. However, less than half of the patients responded positively to treatment. Acute axonal neuropathy may be a risk factor for a poor prognosis.

[Emission Inventory of Atmospheric Pollutants and VOC Species from Crop Residue Burning in Guangdong Province].

An emission inventory of atmospheric pollutants from crop residue burning in Guangdong for the period 2008-2016 was developed, based on crop yield data. Emissions of species of volatile organic compounds(VOCs)and corresponding ozone formation potential (OFP) in 2016 were also estimated. Results showed that emissions of atmospheric pollutants from crop residue burning in 2013-2016 were lower than in 2008-2012. This was mainly due to the policy of prohibiting open burning of straw and to improvement of rural living standards, which reduced the proportion of straw burning. In 2016, emissions of SO2, NOx, NH3, CH4, EC, OC, NMVOC, CO, and PM2.5 were 2443.7, 16187.9, 6943.8, 29174.4, 3625.5, 14830.7, 65612.6, 591613.9, and 49463.0 t, respectively. Rice straw burning was the main source of pollutants, accounting for about 68.55% of total pollutant emissions. The five municipalities with highest atmospheric pollutant emissions were Zhanjiang, Maoming, Meizhou, Zhaoqing, and Shaoguan, together accounting for about 58.63% of total emissions. The top 10 VOC species for mass-based emissions consisted of ethylene, acetaldehyde, formaldehyde, benzene, ethyne, propylene, ethane, toluene, propane, and propionaldehyde, together contributing 67.91% to total emissions. The top ten OFP-based VOC species were ethylene, formaldehyde, acetaldehyde, propylene, 1-butylene, propionaldehyde, toluene, acrolein, isoprene, and crotonaldehyde, accounting for 80.83% of total OFP.

Enhanced Neurogenesis and Collaterogenesis by Sodium Danshensu Treatment After Focal Cerebral Ischemia in Mice.

Ischemic stroke remains a serious threat to human life. There are limited effective therapies for the treatment of stroke. We have previously demonstrated that angiogenesis and neurogenesis in the brain play an important role in functional recovery following ischemic stroke. Recent studies indicate that increased arteriogenesis and collateral circulation are determining factors for restoring reperfusion and outcomes of stroke patients. Danshensu, the Salvia miltiorrhiza root extract, is used in treatments of various human ischemic events in traditional Chinese medicine. Its therapeutic mechanism, however, is not well clarified. Due to its proposed effect on angiogenesis and arteriogenesis, we hypothesized that danshensu could benefit stroke recovery through stimulating neurogenesis and collaterogenesis in the post-ischemia brain. Focal ischemic stroke targeting the right sensorimotor cortex was induced in wild-type C57BL6 mice and transgenic mice expressing green fluorescent protein (GFP) to label smooth muscle cells of brain arteries. Sodium danshensu (SDS, 700 mg/kg) was administered intraperitoneally (i.p.) 10 min after stroke and once daily until animals were sacrificed. To label proliferating cells, 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg, i.p.) was administered, starting on day 3 after ischemia and continued once daily until sacrifice. At 14 days after stroke, SDS significantly increased the expression of vascular endothelial growth factor (VEGF), stromal-derived factor-1 (SDF-1), brain-derived neurotrophic factor (BDNF), and endothelial nitric oxide synthase (eNOS) in the peri-infarct region. SDS-treated animals showed increased number of doublecortin (DCX)-positive cells. Greater numbers of proliferating endothelial cells and smooth muscle cells were detected in SDS-treated mice 21 days after stroke in comparison with vehicle controls. The number of newly formed neurons labeled by NeuN and BrdU antibodies increased in SDS-treated mice 28 days after stroke. SDS significantly increased the newly formed arteries and the diameter of collateral arteries, leading to enhanced local cerebral blood flow recovery after stroke. These results suggest that systemic sodium danshensu treatment shows significant regenerative effects in the post-ischemic brain, which may benefit long-term functional recovery from ischemic stroke.

[Air Quality Subarea Management:A Case Study of Guangdong Province].

To meet the requirements of regional air quality management (AQM), the Air Quality Subarea Management (AQSM) system was proposed. A case study was conducted for Guangdong Province. By using the method of air quality numerical simulation and satellite remote sensing inversion analysis, the key factors were selected from the meteorological simulation field, the pollutant concentration simulation field, and the satellite image interpretation to form the index system for AQSM. On this basis, a hierarchical cluster analysis method was used to divide Guangdong Province into three types of AQSM:Strict Control Subarea, Continuous Improvement Subarea, and Coordinated Development Subarea. It was shown that the Strict Control Subarea, Continuous Improvement Subarea, and Coordinated Development Subarea in Guangdong Province covered 16.3%, 28.0%, and 55.7%, respectively. The Strict Control Subarea in the Pearl River Delta, Eastern Guangdong, Western Guangdong, and Northern Guangdong accounted for 27.9%, 19.3%, 4.4%, and 12.5%, respectively, and the subarea should implement the most stringent AQM policies to promote air quality improvement. The Continuous Improvement Subarea in the Pearl River Delta, Eastern Guangdong, Western Guangdong, and Northern Guangdong accounted for 34.4%, 15.8%, 7.8%, and 34.5%, respectively, and the subarea should implement relatively strict AQM policies to ensure sustained and stable standards. The Coordinated Development Subarea in the Pearl River Delta, Eastern Guangdong, Western Guangdong, and Northern Guangdong accounted for 37.7%, 64.9%, 87.8%, and 53.0%, respectively, and the subarea could implement more liberal AQM policies to ensure relatively good air quality. In general, the strict AQM policies in Guangdong Province should be mainly concentrated in the Pearl River Delta region, followed by Northern Guangdong, Eastern Guangdong, and Western Guangdong in order.

Restless legs syndrome secondary to pontine infarction: Clinical analysis of five cases.

OBJECTIVE: Pontine infarction is a common type of stroke in the cerebral deep structures, resulting from occlusion of small penetrating arteries, may manifest as hemi-paralysis, hemi-sensory deficit, ataxia, vertigo, and bulbar dysfunction, but patients presenting with restless legs syndrome (RLS) are extremely rare. Herein, we reported five cases with RLS as a major manifestation of pontine infarction. METHODS: Five cases of pontine infarction related RLS were collected from July 2013 to February 2016. The diagnosis of RLS was made according to criteria established by the International RLS Study Group (IRLSSG) in 2003. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Severity of RLS was based on the International RLS Rating Scale (IRLS-RS). Sleep quality was assessed by Epworth Rating Scale (ERS), and individual emotional and psychological states were assessed by Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS). RESULTS: The laboratory data at the onset including hemoglobin, serum concentration of homocysteine, blood urea nitrogen (BUN), creatinine, electrolytes, and thyroid hormones were normal. The electroencephalogram (EEG), lower-extremity somatosensory evoked potential (SEP), and nerve conduction velocity (NCV) in four limbs were normal. The average period of follow-up was 34.60 ± 12.76 months. The MRI examination showed acute or subacute pontine infarction lesions, 3 cases in the rostral inner side, 1 case in the rostral lateral and inner side, and 1 case in rostral lateral side. The neurological deficits included weakness in 4 cases, contralateral sensory deficit in 1 case, and ataxia in 2 cases. All 5 patients presented with symptom of RLS at or soon after the onset of infarction and 4 patients experienced uncomfortable sensations in the paralyzed limbs contralateral to the ischemic lesion. Their neurological deficits improved significantly 2 weeks later, but the symptoms of RLS did not resolve. Among them, 3/5 patients were treated with dopaminergic drugs. At the end of the follow-up, RLS symptom eventually resolved in 3 patients but persisted in two. The IRLS-RS, NIHSS and mRS scores were significantly lower at the onset than those at the last follow-up (P = 0.035, 0.024 and 0.049, respectively). However, there was no significant difference in the ERS, HDS and HAS scores (P = 0.477, 0.226 and 0.778, respectively). CONCLUSION: RLS can be an onset manifestation of pontine infarction, clinicians should be aware of this potential symptom. RLS usually occurs in the paralyzed limbs contralateral to the infarction lesion. The pathogenesis still needs further investigation.

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.

OBJECTIVE: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. DATA SOURCES: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation." STUDY SELECTION: Original articles and critical reviews on the topics were selected. RESULTS: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. CONCLUSIONS: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

Association of circulating high-sensitivity C-reactive protein with late recurrence after ischemic stroke.

We investigated the association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and stroke recurrence events in a cohort of patients with acute ischemic stroke (IS). We prospectively studied 286 patients with acute IS who were admitted within 24 h after the onset of symptoms. Serum levels of hs-CRP, and National Institutes of Health stroke scale (NIHSS) were measured at admission. The primary endpoint was stroke recurrence 1 year after stroke onset. We used logistic regression models to assess the relationship between hs-CRP levels and the risk of recurrent stroke. In multivariable models, hs-CRP levels were associated with an increased risk of an NIHSS greater than 6 [odds ratio=1.17; 95% confidence interval (CI)=1.05-1.48; P=0.021]. Among the participants, stroke recurrence was found in 48 (16.8%) cases. In multivariate analyses, the third and fourth quartiles of hs-CRP were significantly associated with stroke recurrence during the observation period compared with the first quartile group (P<0.01). In addition, the hs-CRP level in the highest quartile was associated with a higher risk of stroke recurrence (odds ratio=2.75; 95% CI=1.62-3.92; P=0.006). Hs-CRP (area under the curve=0.71; 95% CI=0.64-0.79) improved the ability of the NIHSS score to diagnose stroke recurrence (area under the curve of the combined model 0.78; 95% CI=0.73-0.84; P<0.01). Serum levels of hs-CRP at admission predicted the future stroke recurrence in patients with IS.

[Clinical observation of axial offset after treatment by Ilizarov bone transport technology].

OBJECTIVE: To observe the incidence, causes and deviation angle of axial offset in patients with fracture ununited treated by Ilizarov bone transport technology. METHODS: From January 2007 to December 2012, 10 patients with fracture ununited were treated by Ilizarov bone transport including 8 males and 2 females with an average age of (30.3 ± 10.6) years old ranging from 18 to 49 years old. The segment of bone defect involved upper tibial in 2 cases, medial tibia in 2 cases, lower tibial in 5 cases, upper femoral in 1 case. For Paley type of bone defect, 6 cases were type B1, 4 cases were B3. The incidence and deviation angle of axial offset after Ilizarov bone transport technology were observed and evaluated on bone result by Paley assessment. RESULTS: All patients were followed up from 19 to 32 months with an average of (22.0 ± 5.6) months. Three cases were natural healed at fracture ends, the other 7 cases were healed after bone graft. The time of external fixator was 16 to 28 months. At the last follow-up, there were 3 cases occurred coronal angulation of angle 5° to 11° with an average of (8.7 ± 3.2). Sagittal angulation was in 4 cases, angle 6° to 9° with an average of (8.5 ± 2.1)°. There were 4 cases occurred axial offset. In the last follow-up, according to Paley evaluation criteria, osseous results were excellent in 7 cases, good in 3 cases; functional results were excellent in 6 cases, good in 4 cases. CONCLUSION: Axial deviation after the Ilizarov bone transport treatment is relatively common, which will result in delayed healing of bone and poor limb alignment. In order to improve the bone healing, corresponding measurements should be taken to avoid or reduce the incidence of axial deviation during and after the operation.

Risk factors for preoperative respiratory complications in children with tracheobronchial foreign bodies.

OBJECTIVE: To identify risk factors for preoperative respiratory complications associated with tracheobronchial foreign body aspiration (TFBA) by retrospectively analysing paediatric cases presenting with or without complications. METHODS: Paediatric patients who presented with TFBA and were admitted to hospital were enrolled in the study. Patients were divided into two groups based on occurrence of preoperative respiratory complications as confirmed by computed tomography. Age, sex, TFBA symptoms, type of foreign body, retention timeand location of the foreign body were documented and compared between the groups. RESULTS: In total, 223 children were included: group A (n = 161) included those with respiratory complications; group B (n = 62) included those without respiratory complications. Univariate and multivariate analyses found that type of foreign body, and symptoms differed significantly between the two groups. CONCLUSION: Respiratory complications of TFBA in children were correlated with the type of foreign body and symptoms.