Moxibustion for declined cardiorespiratory fitness of apparently healthy older adults: A study protocol for a randomized controlled trial.

BACKGROUND: Aging and age-related declines lead to varying degrees of decreased cardiorespiratory fitness (CRF) in apparently healthy older adults. Exercise training, the primary approach for enhancing CRF, encounters several constraints when used with elderly individuals. Existing evidence implies that moxibustion might enhance the CRF of older adults. However, clinical research in this area still needs to be improved. METHODS: This study will employ a randomized, assessor-blinded, controlled trial design involving 126 eligible participants. These participants will be stratified and randomly assigned to one moxibustion group, one sham moxibustion group, and one blank control group. Acupoints of bilateral Zusanli (ST36), Shenque (CV8), and Guanyuan (CV4) are selected for both real and sham moxibustion groups. The treatment will last 60 min per session, 5 sessions a week for 12 weeks. The blank control group will not receive any intervention for CRF improvement. Primary outcomes will be the mean change in peak oxygen uptake (VO2peak), anaerobic threshold (AT), and serum central carbon metabolites (CCB) from the baseline to observation points. Secondary outcome measures involve the six-minute walk distance (6MWD), the Short Form 36 Health Survey (SF-36), and the Qi and Blood Status Questionnaire (QBSQ). Outcome assessments will be conducted at weeks 4, 8, 12, and 24 as part of the follow-up. Adverse events will be assessed at each visit. DISCUSSION: This trial can potentially ascertain moxibustion's effectiveness and safety in enhancing CRF among apparently healthy older adults. TRAIL REGISTRATION: ChiCTR, ChiCTR2300070303. Registered on April 08, 2023.

Effect of MEP-oriented scalp acupuncture combined with transcranial magnetic stimulation on limb motor ability in patients with ischemic stroke hemiplegia. / MEPå®šä½ä¸‹å¤´é’ˆè”åˆç»é¢ ç£åˆºæ¿€å¯¹ç¼ºè¡€æ€§è„‘å’ä¸­åç˜«æ‚£è€ è‚¢ä½“è¿åŠ¨èƒ½åŠ›çš„å½±å“.

OBJECTIVES: To observe the effect of motor evoked potential (MEP)-oriented scalp acupuncture combined with transcranial magnetic stimulation (TMS) on limb motor ability in patients with ischemic stroke hemiplegia. METHODS: A total of 60 patients with ischemic stroke hemiplegia were randomized into an observation group and a control group, 30 cases in each one. In addition to the medication treatment of internal medicine and comprehensive training of hemiplegic limbs, MEP-oriented scalp acupuncture combined with TMS was applied in the observation group, conventional scalp acupuncture at bilateral anterior oblique line of parietal and temporal regions combined with TMS was applied in the control group. The treatment was given once a day, 5 days a week for 4 weeks totally in the two groups. Before and after treatment, the scores of Fugl-Meyer assessment (FMA), modified Ashworth scale (MAS) and modified Barthel index (MBI) were observed in the two groups. RESULTS: After treatment, the FMA and MBI scores were increased compared with those before treatment in the two groups (P<0.001), and the FMA and MBI scores in the observation group were higher than those in the control group (P<0.05). After treatment, the MAS scores of upper and lower limbs in the observation group were decreased compared with those before treatment (P<0.01, P<0.001), the MAS score of lower limb in the control group was decreased compared with that before treatment (P<0.05). CONCLUSIONS: MEP-oriented scalp acupuncture combined with TMS can effectively improve the limb motor ability, daily living ability and limb spasticity in patients with ischemic stroke hemiplegia.

Effects of zhongfeng cutong moxibustion on motor function and corticospinal tract in the patients with motor dysfunction during the recovery period of cerebral infarction. / ä¸­é£Žä¿ƒé€šç¸å¯¹è„‘æ¢—æ­»æ¢å¤æœŸè¿åŠ¨åŠŸèƒ½éšœç¢æ‚£è€ è¿åŠ¨åŠŸèƒ½åŠçš®è´¨è„Šé«“æŸçš„å½±å“.

OBJECTIVES: To observe the effects of zhongfeng cutong moxibustion (moxibustion therapy for unblocking and treating stroke) on the motor function and the structure of corticospinal tract (CST) in the patients with motor dysfunction during the recovery period of cerebral infarction, and to explore the central mechanism of this moxibustion therapy for improving the motor function. METHODS: Fifty patients with motor dysfunction during the recovery period of cerebral infarction were randomly divided into an observation group (25 cases, 1 case dropped out) and a control group (25 cases, 1 case dropped out). The patients in both groups underwent the conventional basic treatment. In the control group, acupuncture was applied to Baihui (GV 20) and Shuigou (GV 26), as well as Chize (LU 5), Neiguan (PC 6), Weizhong (BL 40) and Sanyinjiao (SP 6) etc. on the affected side. Besides the intervention of the control group, in the observation group, zhongfeng cutong moxibustion therapy was combined at Baihui (GV 20), Shenque (CV 8) and bilateral Zusanli (ST 36). Both acupuncture and moxibustion therapies were delivered once daily, 5 times a week, for 2 weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were compared between the two groups before and after treatment. The diffusion tensor imaging technique was used to observe the fractional anisotropy (FA) of CST at the bilateral whole segment, the cerebral cortex, the posterior limb of the internal capsule and the cerebral peduncle before and after treatment in the two groups. RESULTS: The scores of the upper and the lower limbs of FMA, as well as the total FMA score swere increased after treatment when compared with those before treatment in the two groups (P<0.05), the upper limb FMA score and the total FMA score in the observation group were higher than those in the control group (P<0.05), and NIHSS scores of the two groups were dropped compared with those before treatment (P<0.01). FA of CST at the bilateral sides of the posterior limb of the internal capsule and the whole segment on the focal side was improved in comparison with that before treatment in the observation group (P<0.05), and FA of CST at the healthy side of the whole segment was higher than that before treatment in the control group (P<0.05). CONCLUSIONS: Zhongfeng cutong moxibustion improves motor function and reduces neurological deficits in the patients with motor dysfunction during the recovery period of cerebral infarction, which may be related to enhancing the remodeling of white matter fiber bundles in the corticospinal tract on the focal side of the whole segment and the bilateral posterior limb of the internal capsule.

Case report: Extrapontine myelinolysis combined with flupentixol- and melitracen-induced dysphagia.

Extrapontine myelinolysis (EPM) is a rare symmetrical demyelinating disease of the central nervous system, which is often accompanied with central pontine myelinolysis (CPM) or can appear alone. A combination of flupentixol and melitracen is used as an antianxiety-antidepressant drug which may induce hyponatremia. Herein, we report a 46-year-old woman with depression who was treated with flupentixol and melitracen 0.5/10 mg once daily for 6 months. Later, the dosage increased to 0.5/10 mg twice daily. At the same time, she had complains of intermittent dizziness and fatigue. The laboratory test revealed hyponatremia (121 mmol/L). Dizziness was improved after sodium supplementation, with an increase in blood sodium to 133 mmol/L. Twenty days later, she had difficulty opening the mouth and swallowing, needing a gastric tube due to severe dysphagia. Head magnetic resonance imaging (MRI) showed a symmetric abnormal signal of caudate nucleus and lenticular nuclei. The symptoms were not relieved after active treatment, such as rehydration. However, her symptoms improved significantly after discontinuation of flupentixol and melitracen and switching to promethazine. Follow-up head MRI after 4 months revealed no abnormal signals. The patient who developed EPM had dysphagia, despite appropriate correction of hyponatremia. Flupentixol and melitracen can cause hyponatremia and dysphagia. This case highlights an unexpected association between EPM and flupentixol- and melitracen-induced dysphagia.

[ZHANG Jian-bin's clinical experience in treatment of depressive disorder based on the theory of governor vessel].

Depressive disorder is manifested as emotional and physical abnormality. Theoretically, the governor vessel is distributed along the spine, related to the brain and communicated with five zang and six fu organs. It is the key meridian for understanding the various symptoms of depressive disorder. Depressive disorder is caused by dysfunction, stagnation or emptiness of the governor vessel, resulting in malnutrition of the brain. In clinical diagnosis and treatment, based on the theory of the governor vessel, the etiology and pathogenesis are analyzed in the patients with depressive disorder. In order to achieve harmonizing mutually the mental and physical conditions, acupuncture is delivered to adjust the spirit and physical state, moving cupping is to regulate the governor vessel, tuina manipulation is to promote meridians and collaterals and physical exercise is to coordinate the body and the spirit.

Anti-GT1a and anti-GQ1b immunoglobulin G antibody positivity with overlapping Miller Fisher/Guillain-Barré syndromes and prominent headache: a case report.

Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are acute immune-mediated peripheral neuropathies. In addition to their classic presentations, a variety of other signs and symptoms have been reported; however, headache appears to be relatively uncommon. We describe a 53-year-old woman who presented with acute bulbar palsy as the first symptom of overlapping MFS/GBS accompanied by severe headache. The first important clinical impairment of the patient was acute bulbar palsy along with prominent headache, without limb weakness. Although her initial diagnosis was acute bulbar palsy plus, she subsequently developed lower limb diffuse weakness, and her final clinical diagnosis was overlapping MFS/GBS. Anti-ganglioside antibodies were positive for anti-GQ1b and anti-GT1a immunoglobulin G. The patient received intravenous immunoglobulin on day 2 of admission. Early identification of these overlapping syndromes is important for the management of patients, to avoid respiratory failure or severe weakness with axonal degeneration. We therefore remind clinicians of the importance of further examination in patients with headache and acute bulbar palsy of unknown origin.

[Professor ZHANG Jian-bin's clinical experience in "moving cupping therapy on the back"].

This paper summarizes Professor ZHANG Jian-bin's experience in "moving cupping therapy on the back" in clinical practice. Professor ZHANG Jian-bin is good at applying the theory of governor vessel to the clinical diagnosis and treatment. He believes that the moving cupping therapy is the supplementation of "spinal therapy" in clinical diagnosis and treatment. He emphasizes that during the moving cupping therapy exerted, the physicians should observe carefully to in-time obtain the perceived feedback of treatment in patients. Afterward, the cupping marks left should be inspected to discover the location of disorder in the body, thus, a targeted treatment can be provided. Besides, the prognosis of the disease can be judged by the feedback after many treatments with the moving cupping therapy. The moving cupping therapy displays its important value in the diagnosis and treatment of disease, as well as the evaluation of the prognosis.

[Progress of researches on involvement of corticospinal tract in the effect of acupuncture on improvement of post-stroke motor dysfunction].

The corticospinal tract (CST), descending from the frontoparietal cortex and traveling down to terminate at the anterior horn of the spinal cord to mediate voluntary movements, is frequently injured from the infarcted or hemorrhagic cerebrovascular insults due to stroke. Under the circumstances, motor dysfunction seriously affects the patient's quality of life. Acupuncture therapy has a sequelae, especially in improving motor deficits. In the present paper, we reviewed the current development of researches on acupuncture treatment of poststroke motor dysfunction and its biological mechanisms from 1) delaying patients' development of neuronal degeneration and white matter fibrosis (Wallerian degeneration), 2) improving patients' upper limb motor function and daily life ability by promoting the repair of white matter tracts and CST on the affected side, 3) promoting the compensation of CST on the healthy side, 4) reconstructing the motor conduction pathway to strengthen the bilateral brain connection in ex-perimental animals, and 5) strengthening the sprouting of the contralateral CST to dominate the affected side again across the midline. In addition, acupuncture stimulation induced improvement of axonal rewiring for corticospinal innervation is also possibly related to its functions in accelerating the synthesis and release of neurotrophic factors, down-regulating Nogo-A/RhoA signaling and activating vascular epithelial growth factor/Dll4/Notch signaling pathways.

Evaluation of a lung cancer screening programme attracting a cohort to actively participate in screening: Honghe Lung Cancer Medical Center Programme.

Background: A lung cancer screening project was conducted by attracting active participation to evaluate its feasibility and effectiveness in areas with poor basic medical education. Methods: This project entailed a prospective, single-arm study which was conducted by means of delivering a lecture on lung cancer at the Honghe Lung Cancer Medical Center to attract public attention and attendance from 28 November 2020 to 21 December 2021. A questionnaire comprising 7 high-risk factors was completed by participants to identify high-risk individuals for further chest low-dose computed tomography examination. Non calcified nodules with a diameter ≥5 mm were deemed positive nodules. The positive nodules were discussed by a multidisciplinary team and treatment suggestions were given. Finally, we analyzed participant information, examination adherence, lung cancer detection rate, and staging. Results: A total of 6,121 individuals were attracted to the project, and 5,925 (96.8%) agreed to participate. Of these, 5,889 (99.4%) completed the survey, with 4,627 (78.6%) in the high-risk group and 1,262 (21.4%) in the non-high-risk group. The proportion of males in the high-risk group was higher than that in the non-high-risk group, and the difference was statistically significant among those aged 40-49 years, 50-59, years and 60-69 years; P<0.01. In the high-risk population, 4,536 (98.0%) of participants adhered to examination, among whom 2,007 (44.2%) with positive nodules, 1,220 (26.9%) with negative nodules, and 1,309 (28.9%) without nodules showed statistical differences in age; P<0.01. The detection rate of lung cancer was 2.2% (99/4,536); 94.0% (93/99) of whom were stage 0-I patients. Conclusions: A health lecture-based approach to improving public participation in regions with poor health education is likely to be effective in promoting the early detection of lung cancer.

Formyl peptide receptor 1 signaling potentiates inflammatory brain injury.

Acute brain insults elicit pronounced inflammation that amplifies brain damage in intracerebral hemorrhage (ICH). We profiled perihematomal tissue from patients with ICH, generating a molecular landscape of the injured brain, and identified formyl peptide receptor 1 (FPR1) as the most abundantly increased damage-associated molecular pattern (DAMP) receptor, predominantly expressed by microglia. Circulating mitochondrial N-formyl peptides, endogenous ligands of FPR1, were augmented and correlated with the magnitude of brain edema in patients with ICH. Interactions of formyl peptides with FPR1 activated microglia, boosted neutrophil recruitment, and aggravated neurological deficits in two mouse models of ICH. We created an FPR1 antagonist T-0080 that can penetrate the brain and bind both human and murine FPR1. T-0080 attenuated brain edema and improved neurological outcomes in ICH models. Thus, FPR1 orchestrates brain inflammation after ICH and could be targeted to improve clinical outcome in patients.

Brain transforms natural killer cells that exacerbate brain edema after intracerebral hemorrhage.

Perihematomal edema (PHE) occurs within hours after intracerebral hemorrhage (ICH), leading to secondary injury manifested by impaired blood-brain barrier (BBB) integrity and destruction of adjacent tissue. To dissect the mechanisms underlying PHE formation, we profiled human and mouse perihematomal tissues and identified natural killer (NK) cells as the predominant immune cell subset that outnumbers other infiltrating immune cell types during early stages of ICH. Unbiased clustering of single-cell transcriptional profiles revealed two major NK cell subsets that respectively possess high cytotoxicity or robust chemokine production features in the brain after ICH, distinguishing them from NK cells of the periphery. NK cells exacerbate BBB disruption and brain edema after ICH via cytotoxicity toward cerebral endothelial cells and recruitment of neutrophils that augment focal inflammation. Thus, brain-bound NK cells acquire new features that contribute to PHE formation and neurological deterioration following ICH.

Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD. METHODS: We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with highly relapsing NMOSD diagnosed according to 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, who had an Expanded Disability Status Scale (EDSS) score of 7·5 or lower, and had a history of at least two clinical relapses during the previous 12 months or three relapses during the previous 24 months with at least one relapse within the previous 12 months. Patients were randomly assigned (1:1) to intravenous tocilizumab (8 mg/kg every 4 weeks) or oral azathioprine (2-3 mg/kg per day) by an independent statistician using computer-generated randomisation software with permuted blocks of four. The central review committee, EDSS raters, laboratory personnel, and radiologists were masked to the treatment assignment, but investigators and patients were aware of treatment allocation. The minimum planned duration of treatment was 60 weeks following randomisation. The primary outcome was time to first relapse in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, and the per-protocol population, which included all patients who used azathioprine or tocilizumab as monotherapy. For the analyses of the primary outcome, the patients were prespecified into two subgroups according to concomitant autoimmune disease status. Safety was assessed in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03350633. FINDINGS: Between Nov 1, 2017, and Aug 3, 2018, we enrolled 118 patients, of whom 59 were randomly assigned to tocilizumab and 59 were randomly assigned to azathioprine. All 118 patients received one dose of study drug and were included in the full analysis set. 108 participants were included in the per-protocol analysis (56 in the tocilizumab group and 52 in the azathioprine group). In the full analysis set, median time to the first relapse was longer in the tocilizumab group than the azathioprine group (78·9 weeks [IQR 58·3-90·6] vs 56·7 [32·9-81·7] weeks; p=0·0026). Eight (14%) of 59 patients in the tocilizumab group and 28 (47%) of 59 patients in the azathioprine group had a relapse at the end of the study (hazard ratio [HR] 0·236 [95% CI 0·107-0·518]; p<0·0001). In the per-protocol analysis, 50 (89%) of 56 patients in the tocilizumab group were relapse-free compared with 29 (56%) of 52 patients in the azathioprine group at the end of the study (HR 0·188 [95% CI 0·076-0·463]; p<0·0001); the median time to first relapse was also longer in the tocilizumab group than the azathioprine group (67·2 weeks [IQR 47·9-77·9] vs 38·0 [23·6-64·9]; p<0·0001). In the prespecified subgroup analysis of the full analysis set stratified by concomitant autoimmune diseases, among patients without concomitant autoimmune diseases, three (9%) of 34 patients in the tocilizumab group and 13 (35%) of 37 patients in the azathioprine group had relapsed by the end of the study. Among patients with concomitant autoimmune diseases, a lower proportion of patients in the tocilizumab group had a relapse than in the azathioprine group (five [20%] of 25 patients vs 15 [68%] of 22 patients; HR 0·192 [95% CI 0·070-0·531]; p=0·0004). 57 (97%) of 59 patients in the tocilizumab group and 56 (95%) of 59 patients in the azathioprine group had adverse events. Treatment-associated adverse events occurred in 36 (61%) of 59 tocilizumab-treated patients and 49 (83%) of 59 azathioprine-treated patients. One death (2%) occurred in the tocilizumab group and one (2%) in the azathioprine group, but neither of the deaths were treatment-related. INTERPRETATION: Tocilizumab significantly reduced the risk of a subsequent NMOSD relapse compared with azathioprine. Tocilizumab might therefore be another safe and effective treatment to prevent relapses in patients with NMOSD. FUNDING: Tianjin Medical University, Advanced Innovation Center for Human Brain Protection, National Key Research and Development Program of China, National Science Foundation of China.

Inhibition of activator protein 1 attenuates neuroinflammation and brain injury after experimental intracerebral hemorrhage.

AIMS: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP-1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP-1 and neuroinflammation-associated brain injury triggered by ICH. METHODS: Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP-1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP-1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro. RESULTS: AP-1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. Inhibition of AP-1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL-6 and TNF-α production and brain-infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin-induced production of IL-6 and TNF-α in cultured microglia. CONCLUSIONS: Inhibition of AP-1 curbs neuroinflammation and reduces brain injury following ICH.

Inhibition of fibrin formation reduces neuroinflammation and improves long-term outcome after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a severe type of stroke without effective treatment. The coagulation cascade is activated after blood flows into the brain parenchyma. The conversion of fibrinogen to fibrin is an essential step of coagulation processes, but its influences on neuroinflammation and long-term outcome after ICH have not been adequately studied. Hirudin binds to thrombin and inhibits the conversion of fibrinogen to fibrin. We therefore investigated the impact of hirudin treatment on brain inflammation and long-term outcome of ICH in mice. METHODS: Fibrinogen levels were measured in plasma samples from patients with ICH. In mice subjected to collagenase injection, fibrinogen levels were measured in the plasma and brain. The impact of hirudin on neuroinflammation and long-term neurological outcome was determined in ICH mice. RESULTS: Circulating fibrinogen level was increased in patients with ICH at day 1 and day 4 after onset. In ICH mice, fibrinogen levels in the blood and brain were increased at day 7. Delayed daily administration of hirudin from day 7 to day 28 significantly improved long-term outcome in ICH mice. Hirudin treatment reduced leukocyte accumulation in the brain and shifted microglia toward an anti-inflammatory phenotype. In addition, depletion of microglia in ICH mice diminished the benefit of hirudin in ICH mice. CONCLUSIONS: These results suggest that inhibition of fibrin formation alleviates brain inflammation and improves long-term outcome after ICH.

Limbic encephalitis with relapsing polychondritis: persistent white matter lesions and brain atrophy.

Relapsing polychondritis (RP) is a rare autoimmune disorder affecting cartilage. Limbic encephalitis is a rare central nervous system manifestation of RP. This current case report describes a 66-year-old Chinese male patient who complained of developing myoclonus in the left leg, ataxia and speech difficulties 3 weeks prior to hospital admission. The patient presented with cognitive impairment, sleep disorder and extrapyramidal symptoms. The patient was diagnosed with RP that affected auricular cartilage, which also manifested as limbic encephalitis. Magnetic resonance imaging showed bilateral temporal lobe lesions involving the hippocampi and basal ganglia. Signal abnormalities in the white matter persisted during the 15-month follow-up period after treatment with corticosteroids and intravenous immunoglobulin. Over the same period, the bilateral hippocampi showed significant atrophy.

Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow.

OBJECTIVE: The present study was undertaken to determine the efficacy of coadministration of fingolimod with alteplase in acute ischemic stroke patients in a delayed time window. METHODS: This was a prospective, randomized, open-label, blinded endpoint clinical trial, enrolling patients with internal carotid artery or middle cerebral artery proximal occlusion within 4.5 to 6 hours from symptom onset. Patients were randomly assigned to receive alteplase alone or alteplase with fingolimod. All patients underwent pretreatment and 24-hour noncontrast computed tomography (CT)/perfusion CT/CT angiography. The coprimary endpoints were the decrease of National Institutes of Health Stroke Scale scores over 24 hours and the favorable shift of modified Rankin Scale score (mRS) distribution at day 90. Exploratory outcomes included vessel recanalization, anterograde reperfusion, and retrograde reperfusion of collateral flow. RESULTS: Each treatment group included 23 patients. Compared with alteplase alone, patients receiving fingolimod plus alteplase exhibited better early clinical improvement at 24 hours and a favorable shift of mRS distribution at day 90. In addition, patients who received fingolimod and alteplase exhibited a greater reduction in the perfusion lesion accompanied by suppressed infarct growth by 24 hours. Fingolimod in conjunction with alteplase significantly improved anterograde reperfusion of downstream territory and prevented the failure of retrograde reperfusion from collateral circulation. INTERPRETATION: Fingolimod may enhance the efficacy of alteplase administration in the 4.5- to 6-hour time window in patients with a proximal cerebral arterial occlusion and salvageable penumbral tissue by promoting both anterograde reperfusion and retrograde collateral flow. These findings are instructive for the design of future trials of recanalization therapies in extended time windows. Ann Neurol 2018;84:725-736.

Bidirectional degeneration in the visual pathway in neuromyelitis optica spectrum disorder (NMOSD).

OBJECTIVE: This study aims to investigate whether bidirectional degeneration occurs within the visual pathway and, if so, the extent of such changes in neuromyelitis optica spectrum disorder (NMOSD). METHODS: In total, 36 NMOSD and 24 healthy controls (HCs) were enrolled. Three-dimensional T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging were used to analyze damage to the posterior visual pathway. Damage to the anterior visual pathway was measured by optical coherence tomography. RESULTS: In total, 24 NMOSD with prior optic neuritis (NMOON) patients showed significant reduction of peripapillary retinal nerve fiber layer, inner and outer retinal thickness, lateral geniculate nucleus volume, primary visual cortex volume, and decreased integrity of optic radiations, compared with 12 NMOSD without prior optic neuritis (NMONON) patients and 24 HCs. In NMONON, only the inner retinal thickness and the integrity of optic radiations were significantly reduced in comparison with HCs. Moreover, patients with optic neuritis showed severe bidirectional degeneration, the loss of the RNFL was greater than the atrophy of V1. CONCLUSION: Our study indicated the presence of trans-synaptic degeneration in NMOSD. Damage to the inner retina and optic radiations can be observed even in NMONON. After an episode of optic neuritis, the anterior visual pathway damage is greater than the posterior visual pathway damage.

Decreased plasma miR-335 expression in patients with acute ischemic stroke and its association with calmodulin expression.

Objective To determine the expression and clinical significance of plasma miR-335 in patients with acute ischemic stroke (AIS) and investigate its association with calmodulin (CaM) expression. Methods Plasma miR-335 and CaM expression levels in patients with AIS and healthy controls were examined. Correlations between miR-335, CaM, and National Institutes of Health Stroke Scale scores were also analysed. Furthermore, the potential regulatory function of miR-335 on CaM expression was investigated. Results Plasma miR-335 levels were significantly lower in AIS and negatively correlated with NIHSS scores. The converse was observed for plasma CaM levels. Plasma miR-335 and CaM levels were negatively correlated. Plasma miR-335 was confirmed as a novel biomarker for AIS diagnosis and an independent predictor of AIS. Up-regulation of miR-335 suppressed CaM protein expression, and CaM was confirmed as a direct target of miR-335. Conclusions Plasma miR-335 was down-regulated in AIS patients and represents a potential noninvasive circulating biomarker.

Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic Stroke: A Pilot Trial.

BACKGROUND: Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke treated within the first 4.5 hours of symptom onset. METHODS AND RESULTS: In this multicenter trial, we randomly assigned 25 eligible patients with hemispheric ischemic stroke stemming from anterior or middle cerebral arterial occlusion to receive alteplase alone and 22 patients to receive alteplase plus oral fingolimod 0.5 mg daily for 3 consecutive days within 4.5 hours of the onset of ischemic stroke. Compared with patients who received alteplase alone, patients who received the combination of fingolimod with alteplase exhibited lower circulating lymphocytes, smaller lesion volumes (10.1 versus 34.3 mL; P=0.04), less hemorrhage (1.2 versus 4.4 mL; P=0.01), and attenuated neurological deficits in National Institute of Health Stroke Scales (4 versus 2; P=0.02) at day 1. Furthermore, restrained lesion growth from day 1 to 7 (-2.3 versus 12.1 mL; P<0.01) with a better recovery at day 90 (modified Rankin Scale score 0-1, 73% versus 32%; P<0.01) was evident in patients given fingolimod and alteplase. No serious adverse events were recorded in all patients. CONCLUSIONS: In this pilot study, combination therapy of fingolimod and alteplase was well tolerated, attenuated reperfusion injury, and improved clinical outcomes in patients with acute ischemic stroke. These findings need to be tested in further clinical trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02002390.

Performance comparison between Logistic regression, decision trees, and multilayer perceptron in predicting peripheral neuropathy in type 2 diabetes mellitus.

BACKGROUND: Various methods can be applied to build predictive models for the clinical data with binary outcome variable. This research aims to explore the process of constructing common predictive models, Logistic regression (LR), decision tree (DT) and multilayer perceptron (MLP), as well as focus on specific details when applying the methods mentioned above: what preconditions should be satisfied, how to set parameters of the model, how to screen variables and build accuracy models quickly and efficiently, and how to assess the generalization ability (that is, prediction performance) reliably by Monte Carlo method in the case of small sample size. METHODS: All the 274 patients (include 137 type 2 diabetes mellitus with diabetic peripheral neuropathy and 137 type 2 diabetes mellitus without diabetic peripheral neuropathy) from the Metabolic Disease Hospital in Tianjin participated in the study. There were 30 variables such as sex, age, glycosylated hemoglobin, etc. On account of small sample size, the classification and regression tree (CART) with the chi-squared automatic interaction detector tree (CHAID) were combined by means of the 100 times 5-7 fold stratified cross-validation to build DT. The MLP was constructed by Schwarz Bayes Criterion to choose the number of hidden layers and hidden layer units, alone with levenberg-marquardt (L-M) optimization algorithm, weight decay and preliminary training method. Subsequently, LR was applied by the best subset method with the Akaike Information Criterion (AIC) to make the best used of information and avoid overfitting. Eventually, a 10 to 100 times 3-10 fold stratified cross-validation method was used to compare the generalization ability of DT, MLP and LR in view of the areas under the receiver operating characteristic (ROC) curves (AUC). RESULTS: The AUC of DT, MLP and LR were 0.8863, 0.8536 and 0.8802, respectively. As the larger the AUC of a specific prediction model is, the higher diagnostic ability presents, MLP performed optimally, and then followed by LR and DT in terms of 10-100 times 2-10 fold stratified cross-validation in our study. Neural network model is a preferred option for the data. However, the best subset of multiple LR would be a better choice in view of efficiency and accuracy. CONCLUSION: When dealing with data from small size sample, multiple independent variables and a dichotomous outcome variable, more strategies and statistical techniques (such as AIC criteria, L-M optimization algorithm, the best subset, etc.) should be considered to build a forecast model and some available methods (such as cross-validation, AUC, etc.) could be used for evaluation.