China Rehabilitation Research Center

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

OBJECTIVE: We aim to summarize reliable evidence of evidence-based medicine for the treatment and prevention of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by analyzing all the published studies on the clinical characteristics of patients with SARS-CoV-2. METHODS: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of SARS-CoV-2 infection were collected for meta-analysis. RESULTS: Ten studies were included in Meta-analysis, including a total number of 50466 patients with SARS-CoV-2 infection. Meta-analysis shows that, among these patients, the incidence of fever was 0.891 (95% CI: 0.818, 0.945), the incidence of cough was 0.722 (95% CI: 0.657, 0.782), and the incidence of muscle soreness or fatigue was 0.425 (95% CI: 0.213, 0.652). The incidence of acute respiratory distress syndrome (ARDS) was 0.148 (95% CI: 0.046, 0.296), the incidence of abnormal chest computer tomography (CT) was 0.966 (95% CI: 0.921, 0.993), the percentage of severe cases in all infected cases was 0.181 (95% CI: 0.127, 0.243), and the case fatality rate of patients with SARS-CoV-2 infection was 0.043 (95% CI: 0.027, 0.061). CONCLUSION: Fever and cough are the most common symptoms in patients with SARS-CoV-2 infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare. The case fatality rate of patients with SARS-CoV-2 infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This meta-analysis also has limitations, so the conclusions of this Meta-analysis still need to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

UNLABELLED: Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17)-mediated immune response has been demonstrated to play a critical role in inflammation-associated disease; however, its role in chronic hepatitis B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV-infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index. In vitro, IL-17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17-associated cytokines was also increased in CHB and ACLF patients. CONCLUSION: Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection.

We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P = .001). Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P = .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR-OCH-12002406.

INTRODUCTION: Early and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival. However, one important consequence of fluid administration is the risk of developing fluid overload (FO), which is associated with increased mortality in patients with acute kidney injury (AKI). We evaluated the impact of fluid balance on mortality in intensive care unit (ICU) patients with AKI. METHODS: The data were extracted from the Beijing Acute Kidney Injury Trial. This trial was a prospective, observational, multicenter study conducted in 30 ICUs among 28 tertiary hospitals in Beijing, China, from 1 March to 31 August 2012. In total, 3107 patients were admitted consecutively, and 2526 patients were included in this study. The data from the first 3 sequential days were analyzed. The AKI severity was classified according to the Kidney Disease: Improving Global Outcomes guidelines. The daily fluid balance was recorded, and the cumulative fluid balance was registered at 24, 48, and 72 h. A multivariate analysis was performed with Cox regression to determine the impact of fluid balance on mortality in patients with AKI. RESULTS: Among the 2526 patients included, 1172 developed AKI during the first 3 days. The mortality was 25.7 % in the AKI group and 10.1 % in the non-AKI group (P < 0.001). The daily fluid balance was higher, and the cumulative fluid balance was significantly greater, in the AKI group than in the non-AKI group. FO was an independent risk factor for the incidence of AKI (odds ratio 4.508, 95 % confidence interval 2.900 to 7.008, P < 0.001) and increased the severity of AKI. Non-surviving patients with AKI had higher cumulative fluid balance during the first 3 days (2.77 [0.86-5.01] L versus 0.93 [-0.80 to 2.93] L, P < 0.001) than survivors did. Multivariate analysis revealed that the cumulative fluid balance during the first 3 days was an independent risk factor for 28-day mortality. CONCLUSIONS: In this multicenter ICU study, the fluid balance was greater in patients with AKI than in patients without AKI. FO was an independent risk factor for the incidence of AKI and increased the severity of AKI. A higher cumulative fluid balance was an important factor associated with 28-day mortality following AKI.

Motor performance is improved by stimulation of the agonist muscle during movement. However, related brain mechanisms remain unknown. In this work, we perform a functional magnetic resonance imaging study in 21 healthy subjects under three different conditions: (1) movement of right ankle alone, (2) movement and simultaneous stimulation of the agonist muscle or (3) movement and simultaneous stimulation of a control area. We constructed weighted brain networks for each condition by using functional connectivity. Network features were analyzed using graph theoretical approaches. We found that (1) the second condition evokes the strongest and most widespread brain activations (5147 versus 4419 and 2320 activated voxels); and (2) this condition also induces a unique network layout and changes hubs and the modular structure of the brain motor network by activating the most “silent” links between primary somatosensory centers and the motor cortex, particularly weak links from the thalamus to the left primary motor cortex. Significant statistical differences were found when the strength values of the right cerebellum (P<0.001) or the left thalamus (P=0.006) were compared among the three conditions. Over the years, studies reported a small number of projections from the thalamus to the motor cortex. This is the first work to present functions of these pathways. These findings reveal mechanisms for enhancing motor function with somatosensory stimulation, and suggest that network function cannot be thoroughly understood when weak ties are disregarded.

Knee osteoarthritis is a chronic degenerative disease. Cartilage and subchondral bone degeneration, as well as synovitis, are the main pathological changes associated with knee osteoarthritis. Mechanical overload, inflammation, metabolic factors, hormonal changes, and aging play a vital role in aggravating the progression of knee osteoarthritis. The main treatments for knee osteoarthritis include pharmacotherapy, physiotherapy, and surgery. However, pharmacotherapy has many side effects, and surgery is only suitable for patients with end-stage knee osteoarthritis. Exercise training, as a complementary and adjunctive physiotherapy, can prevent cartilage degeneration, inhibit inflammation, and prevent loss of the subchondral bone and metaphyseal bone trabeculae. Increasing evidence indicates that exercise training can improve pain, stiffness, joint dysfunction, and muscle weakness in patients with knee osteoarthritis. There are several exercise trainings options for the treatment of knee osteoarthritis, including aerobic exercise, strength training, neuromuscular exercise, balance training, proprioception training, aquatic exercise, and traditional exercise. For Knee osteoarthritis (KOA) experimental animals, those exercise trainings can reduce inflammation, delay cartilage and bone degeneration, change tendon, and muscle structure. In this review, we summarize the main symptoms of knee osteoarthritis, the mechanisms of exercise training, and the therapeutic effects of different exercise training methods on patients with knee osteoarthritis. We hope this review will allow patients in different situations to receive appropriate exercise therapy for knee osteoarthritis, and provide a reference for further research and clinical application of exercise training for knee osteoarthritis.

NLRP3 inflammasome‐mediated pyroptosis is a proinflammatory programmed cell death pathway, which plays a vital role in functional outcomes after stroke. We previously described the beneficial effects of curcumin against stroke‐induced neuronal damage through modulating microglial polarization. However, the impact of curcumin on microglial pyroptosis remains unknown. Here, stroke was modeled in mice by middle cerebral artery occlusion (MCAO) for 60 minutes and treated with curcumin (150 mg/kg) intraperitoneally immediately after reperfusion, followed by daily administrations for 7 days. Curcumin ameliorated white matter (WM) lesions and brain tissue loss 21 days poststroke and improved sensorimotor function 3, 10, and 21 days after stroke. Furthermore, curcumin significantly reduced the number of gasdermin D + (GSDMD + ) Iba1 + and caspase‐1 + Iba1 + microglia/macrophage 21 days after stroke. In vitro , lipopolysaccharide (LPS) with ATP treatment was used to induce pyroptosis in primary microglia. Western blot revealed a decrease in pyroptosis‐related proteins, e.g., GSDMD‐N, cleaved caspase‐1, NLRP3, IL‐1 β , and IL‐18, following in vitro or in vivo curcumin treatment. Mechanistically, both in vivo and in vitro studies confirmed that curcumin inhibited the activation of the NF‐ κ B pathway. NLRP3 knocked down by siRNA transfection markedly increased the inhibitory effects of curcumin on microglial pyroptosis and proinflammatory responses, both in vitro and in vivo . Furthermore, stereotaxic microinjection of AAV‐based NLRP3 shRNA significantly improved sensorimotor function and reduced WM lesion following curcumin treatment in MCAO mice. Our study suggested that curcumin reduced stroke‐induced WM damage, improved functional outcomes, and attenuated microglial pyroptosis, at least partially, through suppression of the NF‐ κ B/NLRP3 signaling pathway, further supporting curcumin as a potential therapeutic drug for stroke.

N6-Methyladenosine (m6A) is the most prevalent internal modification that occurs in the mRNA of eukaryotes and plays a vital role in the post-transcriptional regulation. Recent studies highlighted the biological significance of m6A modification in the nervous system, and its dysregulation has been shown to be related to degenerative and neurodevelopmental diseases. Parkinson’s disease (PD) is a common age-related neurological disorder with its pathogenesis still not fully elucidated. Reports have shown that epigenetic mechanisms including DNA methylation and histone acetylation, which alter gene expression, are associated with PD. In this study, we found that global m6A modification of mRNAs is down-regulated in 6-OHDA-induced PC12 cells and the striatum of PD rat brain. To further explore the relationship between m6A mRNA methylation and molecular mechanism of PD, we decreased m6A in dopaminergic cells by overexpressing a nucleic acid demethylase, FTO, or by m6A inhibitor. The results showed that m6A reduction could induce the expression of N-methyl-d-aspartate (NMDA) receptor 1, and elevate oxidative stress and Ca2+ influx, resulting in dopaminergic neuron apoptosis. Collectively, m6A modification may play a vital role in the death of dopaminergic neuron, which provides a novel view of mRNA methylation to understand the epigenetic regulation of Parkinson’s disease.

BACKGROUND: Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect. RESULTS: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI. CONCLUSION: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. Video Abstract.

AIMS: Microglia and infiltrated macrophages play important roles in inflammatory processes after ischemic stroke. Modulating microglia/macrophage polarization from pro-inflammatory phenotype to anti-inflammatory state has been suggested as a potential therapeutic approach in the treatment of ischemic stroke. Melatonin has been shown to be neuroprotective in experimental stroke models. However, the effect of melatonin on microglia polarization after stroke and underlying mechanisms remain unknown. METHODS: In vivo, cerebral ischemia was induced by distal middle cerebral artery occlusion (dMCAO) in C57BL/6J mice. Melatonin was injected intraperitoneally (20 mg/kg) at 0 and 24 hours after ischemia. In vitro, the microglial cell line BV2 was stimulated to the pro-inflammatory state with conditioned media (CM) collected from oxygen-glucose deprivation (OGD) challenged neuronal cell line Neuro-2a (N2a). Real-time PCR was utilized to detect the mRNA expression of microglia phenotype markers. Activation of signal transducer and activator of transcription 3 (STAT3) pathway was determined by Western blot of phosphorylated STAT3 (pSTAT3). A neuron-microglia co-culture system was used to determine whether melatonin can inhibit the neurotoxic effect of pro-inflammatory microglia to post-OGD neurons. RESULTS: Melatonin treatment reduced brain infarct and improved neurological functions 3 days after dMCAO, which was accompanied by decreased expression of pro-inflammatory markers and increased expression of anti-inflammatory markers in the ischemic brain. In vitro studies confirmed that melatonin directly inhibited the pro-inflammatory responses in BV2 cells upon exposure to OGD neuron CM. The microglia possessing pro-inflammatory phenotype exacerbated post-OGD N2a cells death, whereas melatonin reduced such neurotoxic effect. Further, melatonin enhanced the otherwise inhibited pSTAT3 expression in BV2 cells treated with OGD neuron CM. STAT3 blockade significantly reduced the effect of melatonin on microglial phenotype shift. CONCLUSION: Melatonin treatment ameliorates brain damage at least partially through shifting microglia phenotype from pro-inflammatory to anti-inflammatory polarity in a STAT3-dependent manner.

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

Virtual reality is nowadays used to facilitate motor recovery in stroke patients. Most virtual reality studies have involved chronic stroke patients; however, brain plasticity remains good in acute and subacute patients. Most virtual reality systems are only applicable to the proximal upper limbs (arms) because of the limitations of their capture systems. Nevertheless, the functional recovery of an affected hand is most difficult in the case of hemiparesis rehabilitation after a stroke. The recently developed Leap Motion controller can track the fine movements of both hands and fingers. Therefore, the present study explored the effects of a Leap Motion-based virtual reality system on subacute stroke. Twenty-six subacute stroke patients were assigned to an experimental group that received virtual reality training along with conventional occupational rehabilitation, and a control group that only received conventional rehabilitation. The Wolf motor function test (WMFT) was used to assess the motor function of the affected upper limb; functional magnetic resonance imaging was used to measure the cortical activation. After four weeks of treatment, the motor functions of the affected upper limbs were significantly improved in all the patients, with the improvement in the experimental group being significantly better than in the control group. The action performance time in the WMFT significantly decreased in the experimental group. Furthermore, the activation intensity and the laterality index of the contralateral primary sensorimotor cortex increased in both the experimental and control groups. These results confirmed that Leap Motion-based virtual reality training was a promising and feasible supplementary rehabilitation intervention, could facilitate the recovery of motor functions in subacute stroke patients. The study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-OCH-12002238).

BACKGROUND AND PURPOSE: Oxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its underlying mechanisms of action. EXPERIMENTAL APPROACH: A weight-drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed. KEY RESULTS: Astaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor-erythroid 2-related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down-regulated the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro. CONCLUSION AND IMPLICATIONS: Astaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.

OBJECTIVE: To systematically examine the incidence of cognitive impairment in individuals with spinal cord injury (SCI), as well as identify potential contributing and confounding factors. METHODS: Studies quantitatively reporting cognitive ability after spinal cord injury were searched electronically via Medline, CINAHL, Embase, and PsycINFO. Manual screening for references within articles was also performed. A total of 2,481 studies were screened and a total of 70 were included in this review, 21 reporting cognitive function after SCI compared to an able-bodied control group and 49 with no able-bodied controls. Studies were analyzed for the incidence of impairment and the interactions with concomitant traumatic brain injury, psychological or somatic complaints, decentralized cardiovascular control, sleep apnea, neurologic level of injury, and age. RESULTS: There is a high volume of evidence reporting substantial cognitive impairment in individuals with SCI. Potential co-contributors include concomitant brain injury, psychological or somatic comorbidities, decentralized cardiovascular control, and sleep apnea. Cognitive functioning was negatively correlated with age. No clear agreement was found for the incidence of cognitive impairment or its association with level of injury. CONCLUSION: Current evidence suggests that individuals with SCI should be examined and addressed for cognitive impairment. Future studies aimed at identifying potential secondary causative factors should employ stringent controls for co-occurring brain trauma since it appears to be a major contributor and confounder to impaired cognition.

Spinal cord injury（SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of spinal cord injury, but many problems and risks have not been resolved. Some studies have reported that the therapeutic effect of MSCs on spinal cord injury is related to the paracrine secretion of cells. The exosomes secreted by mesenchymal stem cells have therapeutic potential on many diseases. There are abundant pericytes which possess the characteristics of stem cell in the neurovascular unit. Due to the close relationship between pericytes and endothelial cells, the exosomes of pericytes can be uptake by endothelial cells more easily. There are fewer studies about the therapeutic potential of the exosomes derived from pericytes on spinal cord injury now. In this study, exosomes of pericytes were transplanted into the mice with SCI to study the restoration of motor function and explore the underlying mechanism. We found that the exosomes derived from pericytes could reduce pathological changes, improve the motor function, the blood flow and oxygen deficiency after SCI. In addition, the exosomes could improve the endothelial ability to regulate blood flow, protect the blood-spinal cord barrier, reduce edema, decrease the expression of HIF-1α, Bax, Aquaporin-4 and MMP2, increase the expression of Claudin-5, bcl-2 and inhibit apoptosis. The experiments in vitro proved that exosomes derived from pericytes could protect the barrier of spinal cord microvascular endothelial cells under hypoxia condition, which was related to PTEN/AKT pathway. In summary, our study showed that exosomes of pericytes had therapeutic prospects for spinal cord injury.

In Brief Study Design. Prospective, randomized, controlled, multicenter clinical trial. Objective. To compare outcomes of cervical disc arthroplasty with those of anterior cervical decompression and fusion (ACDF) in a Chinese population. Summary of Background Data. Cervical disc arthroplasty has been found to be superior to ACDF for maintaining range of motion (ROM) at the index spinal segment and possibly will avoid abnormal stress to adjacent segments. Methods. A total of 120 patients from 3 large hospitals in China were randomly assigned to treatment with cervical disc arthroplasty (n = 60) using the BRYAN prosthesis or ACDF (n = 60) and were observed postoperatively for 24 months. Results. The 2 groups had similar preoperative demographics and baseline characteristics including ROM, neck disability index, and visual analogue scale for neck and arm pain. The total disc replacement (TDR) group had a significantly longer operation time than the ACDF group (P < 0.001). Outcome data obtained after 24 months revealed a significant difference between the groups in mean change from baseline in ROM at the index level (P < 0.001); ROM was maintained in the TDR group but reduced in the ACDF group. There were no significant between-group differences in the baseline changes in neck disability index or visual analogue scale scores for pain. One patient in the TDR group and 4 patients in the ACDF group required reoperations. Conclusion. At 24 months after surgery, the cervical disc prosthesis yielded good clinical results while maintaining ROM at the index level. Cervical disc arthroplasty appears to be a viable alternative to ACDF. In a prospective, randomized, controlled, multicenter trial, patients who received cervical disc prostheses were compared with patients treated with anterior cervical decompression and fusion (ACDF). At 2-year follow-up, the group receiving the prosthesis had maintained range of motion at the index level, whereas the ACDF group had reduced range of motion.

OBJECTIVE: The incidence of bladder cancer (BC) is common in the world, but its detail mechanisms for occurrence and development remain unclear. Recently, long non-coding RNAs (lncRNAs) have been observed to play an important role in many different diseases. In this research, we mainly explored the role of the RNA component of mitochondrial RNA processing endoribonuclease (lncRNA-RMRP) in bladder cancer. MATERIALS AND METHODS: We used qRT-PCR to detect the expression of lncRNA-RMRP in bladder cancer patients and tumor cells, and the clinical significance was also analyzed. The methyl thiazolyl tetrazolium (MTT) assay was used to detect the cell proliferation, and we used transwell to detect the migration and invasion, after the lncRNA RMRP was inhibited. Western-blot was used to measure the relative protein expression level in bladder cancer cells after transfection with siRNA-NC or siRNA-RMRP. RESULTS: We found that the lncRNA RMRP was highly expressed in bladder cancer tissue, compared with adjacent tissue. We also found that the expression of RMRP was closely related with the size, lymph node metastasis and survival time of patients. What's more, RMRP could promote the proliferation, migration and invasion of BC cell lines via regulating miR-206 as a sponge. CONCLUSIONS: According to the results, we found that lncRNA RMRP was closely related to the progression of bladder cancer, which could be a potential target for treating BC patients.

Inflammation and activation of the neuroendocrine systems comprise important aspects of stroke pathophysiology. The present study investigated whether baseline plasma brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), cortisol and copeptin levels on admission can predict short-term outcomes and mortality after acute ischaemic stroke. The study group consisted of 189 patients who had their first acute ischaemic stroke. Plasma levels of BNP, NT-proBNP, cortisol and copeptin were evaluated to determine their value with respect to predicting functional outcome and mortality within 3 months. As a result of cardiovascular and neurological investigations (including imaging techniques), lesion size, stroke subtype classification and clinical outcome after 3 months were determined. Plasma levels of BNP, NT-proBNP, cortisol and copeptin were associated with stroke severity, as well as short-term functional outcomes. After adjusting for all other significant outcome predictors, NT-proBNP, cortisol and copeptin remained as independent outcome predictors. In the receiver operating characteristic curve analysis, the biomarker panel (including BNP, NT-proBNP, cortisol and copeptin) predicted functional outcome and death within 90 days significantly more efficiently than the National Institute of Health Stroke Scale (NIHSS) or the biomarker alone. Copeptin showed a significantly greater discriminatory ability as a single biomarker compared to BNP, NT-proBNP, cortisol and NIHSS score. These results suggest that a biomarker panel may add valuable and time-sensitive prognostic information in the early evaluation of acute ischaemic stroke. This may provide a channel for interventional therapy in acute stroke.