Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. RESULTS: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. CONCLUSIONS: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546323.

Correlation of Brain Perfusion with White Matter Hyperintensity, Brain Atrophy, and Cognition in Patients with Posterior Cerebral Artery Stenosis and Subjective Cognitive Decline.

BACKGROUND This study aimed to investigate the correlation of brain perfusion with white matter hyperintensity (WMH), brain atrophy, and cognition in patients with moderate to severe posterior cerebral artery stenosis (PCAS). MATERIAL AND METHODS 65 patients with memory decline as the main complaint and no history of brain infarction were recruited from the Department of Neurology of Tongji Hospital. Patients with moderate to severe PCAS were included in case group, and subjects with normal intracranial blood vessels served as controls. The demographics and vascular risk factors were recorded. Montreal Cognitive Assessment (MoCA) was used to evaluate the cognition. CT perfusion imaging was performed, and WASID was employed for the assessment of intracranial artery stenosis. The region of interest (ROI) was analyzed based on the whole brain perfusion. Cranial MRI was performed, and Scheltens scoring system was used for the assessment of WMH on FLAIR. T1 weighed images were obtained, and global cortical atrophy (GCA) scale was employed for the assessment of brain atrophy. The detections of brain perfusion, WMH and brain atrophy were done at centrum ovale, parietal lateral ventricle and basal ganglia layers. RESULTS In PCAS patients we found low perfusion in the antecornu and postcornu blood supply areas at the lateral ventricle, the blood supply area of the anterior cerebral artery, the blood supply area of the posterior cerebral artery, and the blood supply area at the hippocampus as compared with control subjects (p<0.05). As compared with control subjects, the incidence of WMH in the blood supply areas at the deep brain and lateral ventricle was significantly higher in PCAS patients (p<0.05). When compared with controls, the incidence of brain atrophy increased significantly in PCAS patients (p<0.01). Correlation analysis showed the brain perfusion at the blood supply area of the posterior cerebral artery was positively correlated to the total MoCA score and negatively correlated to the severity of WMH at the blood supply area of the posterior cerebral artery (p<0.05). Further analysis showed the brain perfusion at the blood supply area of the posterior cerebral artery was negatively associated with cortex supplied by the posterior cerebral artery, posterior cingulate, and hippocampus (p<0.01). CONCLUSIONS PCAS patients have a higher incidence of brain atrophy, and the perfusion at the area supplied by the posterior cerebral artery is correlated to the severity of brain atrophy and of WMH, as well as to cognition decline.

RNA-Seq Expression Analysis of Enteric Neuron Cells with Rotenone Treatment and Prediction of Regulated Pathways.

The enteric nervous system (ENS) is involved in the initiation and development of the pathological process of Parkinson's disease (PD). The effect of rotenone on the ENS may trigger the progression of PD through the central nervous system (CNS). In this study, we used RNA-sequencing (RNA-seq) analysis to examine differential expression genes (DEGs) and pathways induced by in vitro treatment of rotenone in the enteric nervous cells isolated from rats. We identified 45 up-regulated and 30 down-regulated genes. The functional categorization revealed that the DEGs were involved in the regulation of cell differentiation and development, response to various stimuli, and regulation of neurogenesis. In addition, the pathway and network analysis showed that the Mitogen Activated Protein Kinase (MAPK), Toll-like receptor, Wnt, and Ras signaling pathways were intensively involved in the effect of rotenone on the ENS. Additionally, the quantitative real-time polymerase chain reaction result for the selected seven DEGs matched those of the RNA-seq analysis. Our results present a significant step in the identification of DEGs and provide new insight into the progression of PD in the rotenone-induced model.

Safety and Efficacy of Rotigotine for Treating Parkinson's Disease: A Meta-Analysis of Randomised Controlled Trials.

We aimed to comprehensively analyse the safety and efficiency of rotigotine for treating Parkinson's disease (PD). We conducted systematic literature searches of Cochrane library, PubMed and Embase databases up to April 2016, with 'Rotigotine', 'Parkinson Disease ' and 'Parkinson's disease' as key searching terms. Outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) Part III and Part II scores, 'off' time, adverse events (AEs), serious AEs and discontinuation because of AEs, were compared between rotigotine and placebo groups under a fixed or random effect model. For dichotomous and continuous data, risk ratio (RR) and weighted mean difference with their corresponding 95% confidence intervals (95% CIs) were taken as the effect sizes to calculate merged results. Twelve eligible studies were included. For patients with early or advanced PD, rotigotine could significantly improve UPDRS Part III and Part II scores (p < 0.001) and it had significantly higher incidence of AEs than the placebo (p < 0.001). Regarding discontinuation because of AEs, rotigotine showed a significant advantage over placebo in patients with early PD, whereas the overall result demonstrated no statistically significant difference between the groups. Rotigotine can improve daily living and motor ability of patients with PD, although it has higher incidence of AEs. Rotigotine might be more appropriate for patients with advanced PD than for those with early PD. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Neuroprotective Effects of Poly(ADP-ribose)polymerase Inhibitor Olaparib in Transient Cerebral Ischemia.

Olaparib was the first poly(ADP-ribose)polymerase inhibitor approved by Food and Drug Administration for oncology treatment. However, its neuroprotective effects have not been elucidated. This study aimed to evaluate the effects of olaparib in transient cerebral ischemia. A mouse model of transient middle cerebral artery occlusion was used. Reperfusion was performed at 2 h after ischemia. Different doses of olaparib (1, 3, 5, 10 and 25 mg/kg) were administered intraperitoneally immediately after reperfusion. Twenty-four hours after ischemia, the neurological score was assessed, and grip and string tests were performed to evaluate the behavioral deficits in the mice. Cresyl violet staining was used to assess cerebral edema and the lesion volume. Immunohistochemistry was performed to evaluate the expression of blood-brain barrier proteins collagen IV and claudin-5, as well as extravasation of IgG. Ischemia induced a neurological deficit, which was significantly ameliorated by olaparib at 3 and 5 mg/kg. However, this neuroprotective effect was not observed in mice treated with either low-dose or high-dose olaparib. Both 3 and 5 mg/kg olaparib markedly reduced cerebral infarction volume, but not cerebral edema. The expression of collagen IV decreased after cerebral ischemia, which was improved by olaparib at 3 and 5 mg/kg. These results were confirmed by the reduction of IgG extravasation with olaparib. Olaparib showed clear neuroprotective effects in transient ischemic mice mainly through the reduction of cerebral infarction and blood-brain barrier damage.

Facial asymmetry in patients with hemifacial spasm before and after botulinum toxin A treatment.

Botulinum toxin A (BoNT-A) injection is one of the most widely used methods for hemifacial spasm (HFS) with high efficacy in controlling spasm. However, it is still unknown if esthetic symmetry could be desired as the spasm was controlled by BoNT-A therapy. The purpose of this study is to clarify the facial asymmetric characteristics of HFS patients and if the asymmetry could be amended by BoNT-A injection in the abnormal side. In this prospective analysis, HFS patients were enrolled, who received hemifacial BoNT-A injection and completed follow-up at weeks 2-4. Self-reported improvement and negative influence of facial asymmetry in social life were documented. Facial asymmetry was assessed by the Sunnybrook facial grading system (SFGS) and a new scale created by our clinic-the Symmetry Scale for Hemifacial Spasm (SSHS). Thirty-eight patients were eligible for analysis. Among them, 34 patients (89 %) had marked improvement in spasm after BoNT-A injection. After BoNT-A injection, SFGS showed an improvement of synkinesis (p = 0.01). And SSHS showed an amelioration of resting symmetry in lower face after treatment (p < 0.05). However, SFGS showed a deterioration of voluntary movement in lower face after treatment (p < 0.01). In addition, a deterioration of voluntary movement in upper face and lower face was found in SSHS after treatment (p < 0.01). SSHS composite score showed a deterioration after BoNT-A injection (p = 0.01). In conclusions, BoNT-A was effective in controlling spasm and synkinesis of HFS and improved resting symmetry in lower face, but facial symmetry of voluntary movement deteriorated after hemifacial BoNT-A injection.

Clinical Features and Related Factors of Poststroke Pathological Laughing and Crying: A Case-Control Study.

OBJECTIVES: The purpose of this study was to analyze clinical features and related factors of poststroke pathological laughing and crying (PSPLC) and to differentiate PSPLC patients with and without pseudobulbar signs. METHODS: We performed a case-control study in which 56 patients with PSPLC were matched to 56 control stroke patients by age and gender. The pathological laughing and crying scale was used to identify patients with PSPLC. Characteristics of PSPLC outbursts, presence of pseudobulbar signs and autonomic symptoms, lesion locations, and different clinical data were analyzed. Mild cognitive impairment (MCI) was evaluated by the Montreal Cognitive Assessment. Poststroke anger proneness (PSAP) was evaluated by comparison of the patients' premorbid states. RESULTS: Significantly more patients in the PSPLC group showed MCI, PSAP, and pseudobulbar signs than those in the control group. Most patients with PSPLC showed bilateral multiple lesions and the pons (especially the bilateral paramedian basal and basal-tegmental areas) stood out as the most important lesion location. Logistic regression analysis showed that pontine lesion, MCI, and PSAP were independently related to PSPLC; however, the presence of pseudobulbar signs was not related. PSPLC patients with pseudobulbar signs showed more recurrent strokes in the previous 2 years, more severe neurological deficits, as well as higher severity of PSPLC. In addition, more patients in the group with pseudobulbar signs showed concomitant autonomic symptoms. CONCLUSIONS: PSPLC, MCI, and PSAP could be manifestations of a more general disorder, in which pontine lesion plays an important role. PSPLC patients with pseudobulbar signs and those without show different features.

Polyclonal neural cell adhesion molecule antibody prolongs the effective duration time of botulinum toxin in decreasing muscle strength.

This study aimed to investigate if the effective duration time of botulinum toxin A (Btx-A) could be prolonged by polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab). 175 male SD rats were randomly divided into three major groups: control group (n = 25), Btx-A group (n = 25), and P-NCAM-Ab groups. P-NCAM-Ab groups were composed of five sub-groups, with 25 rats each in the dose-response study. Muscle strength of rat lower limbs was determined using a survey system. The expressions of muscle-specific receptor tyrosine kinase (MuSK) and neural cell adhesion molecule (NCAM) were determined by real-time polymerase chain reactions (RT-PCR) and western blotting (WB). The muscle strength was significantly decreased by Btx-A in Btx-A/P-NCAM-Ab groups compared with normal control group. Besides, the muscle strength of P-NCAM-Ab group was significantly decreased compared with the Btx-A group. The recovery time of muscle strength in P-NCAM-Ab group was significantly longer compared with Btx-A group. RT-PCR and WB assay showed that PNCAM-Ab delayed the increase of MuSK and NCAM after Btx-A injection. P-NCAM-Ab prolongs the effective duration time of Btx-A in decreasing muscle strength, which could provide a novel enhancement in clinical application.

Treatment of Raynaud's phenomenon with botulinum toxin type A.

Raynaud's phenomenon (RP), an episodic vasospasm of the peripheral arteries, is quite common in general population. The current therapies of RP are limited by efficacy, side effects, and polypharmacy concerns. Botulinum toxin type A (BTX-A) local injections have been reported for the treatment of RP, but the injection sites, concentration and dose of BTX-A were different from each other in previous trials. In addition, so far, there have been no reports concerning local injection of BTX-A in Asian RP patients. Ten patients with RP in China were included in this retrospective study. All the patients had intractable pain and were non-responsive to conservative and/or medical therapy. A patterned BTX-A injection was performed in RP patients, guided by ultrasonography. BTX-A was injected as 20 u/ml devoid of preservatives. Outcomes were measured by ultrasonography, surface temperature, visual analog scale (VAS) for clinical symptoms (pain, numbness, stiffness and swelling), and changes in ulcers or gangrene. Overall, a great improvement in artery flow velocity (P < 0.01), surface temperature (P < 0.01), ulcer and VAS for clinical symptoms, was observed after BTX-A local injection. Complications were very rarely found, and no patients complained of hand weakness and bruise. BTX-A patterned injection guided by ultrasonography might be a useful therapeutic tool in the management of intractable RP.

Multifactor analysis for risk factors involved in the fear of falling in patients with chronic stroke from mainland China.

OBJECTIVE: To analyze the risk factors involved in FOF in patients with chronic stroke from mainland China. METHODS: A cohort of 245 patients with chronic stroke were included in this study. Fear of falling severity was assessed using the Activities-specific Balance Confidence (ABC) Scale. Physical function was assessed using the Berg Balance Scale (BBS), the Timed Up and Go Test (TUGT), and the lower extremity of Fugl-Meyer Assessment. Psychosocial function was assessed with the Center for Epidemiologic Studies Depression (CES-D) Scale, the State-Trait Anxiety Inventory, and the Social Support Rating Scale, respectively. All factors related to FOF severity were analyzed by regression analysis. RESULTS: Statistically significant factors affecting FOF severity included age, history of falling, balance, functional mobility, economic burden, and depression. Participants with a history of falls (N = 81) were divided into high (score ≥ 70, N = 19) and low ABC score (score < 70, N = 62) groups. Compared with the low ABC score group, the high ABC score group had higher BBS scores, and lower CES-D scores. CONCLUSIONS: Our findings suggest that - in addition to age, economic burden, and a history of falls - balance, functional mobility, and depression are risk factors associated with FOF in patients with chronic stroke in mainland China.

Homocysteine level and risk of different stroke types: a meta-analysis of prospective observational studies.

BACKGROUND AND AIMS: Inconsistent findings have been reported regarding the association between elevated plasma homocysteine (Hcy) levels and the risk of different types of strokes. We conducted this meta-analysis to identify the association between homocysteine (Hcy) levels and different kinds of strokes or recurrences of strokes. METHODS AND RESULTS: PubMed and Embase databases were searched for relevant studies published prior to April 2013. Only prospective studies that compared elevated Hcy levels with the risk of different types of strokes were selected. Results were presented as the relative risk (RR) and the corresponding 95% confidence intervals (CI) comparing the highest Hcy category group with the lowest Hcy category group. Nine studies composed of 13,284 participants were included. The pooled RR of ischemic strokes when comparing the highest Hcy category group with the lowest Hcy category group was 1.69 (95% CI: 1.29-2.20) in a fixed-effect model. The pooled RR of hemorrhagic strokes and recurrent strokes when comparing the highest Hcy category group with the lowest Hcy category group in a fixed-effect model was 1.65 (95% CI: 0.61-4.45) and 1.76 (95% CI: 1.37-2.24), respectively. CONCLUSIONS: This meta-analysis indicated that elevated Hcy levels are associated with an increased risk for ischemic strokes and recurrent strokes but had no distinct association with hemorrhagic strokes.

IGF-1 antibody prolongs the effective duration time of botulinum toxin in decreasing muscle strength.

Botulinum toxin type-A (Btx-A), a powerful therapeutic tool in various medical specialties, requires repeated injections to maintain its effect. Therefore, novel methods to prolong the effective duration time of Btx-A are highly needed. Rats were assigned to three major groups: control group (n = 30), Btx-A group (n = 30), and IGF-1 Ab groups. IGF-1 Ab groups were composed by sub-groups A1-A5 (each has 25 rats) for the subsequent IGF-1Ab dose-effect study. Muscle strength was determined by a survey system for rat lower limbs nerve and muscle function. Muscle-specific receptor tyrosine kinase (MuSK), Insulin-like growth factor binding protein-5 (IGFBP5), and growth-associated protein, 43-kDa (GAP43) were determined by real-time polymerase chain reactions (PCRs) and Western blot. We found that Btx-A decreased the muscle strength, with a paralysis maintained for 70 days. IGF-1Ab prolonged the effective duration time of Btx-A. Real-time PCRs and Western blot showed that IGF-1Ab delayed the increase of MuSK and IGFBP5 after Btx-A injection, without affecting GAP43. These results indicate that IGF-1Ab might prolong the effective duration time of Btx-A on muscle strength through delaying the increase of MuSK. It would be interesting to determine whether IGF-1Ab can be used as an auxiliary measure to the Btx-A treatment in the future.

Therapeutic efficacy and safety of botulinum toxin type A in trigeminal neuralgia: a systematic review.

Trigeminal neuralgia is a common disorder caused mainly by compression of the trigeminal nerve root by an overlying blood vessel. Pharmacotherapy and surgery are ineffective or unsuitable in many patients. Therefore, other therapeutic modalities have been tried, including injection of botulinum toxin type A (BTX-A). This study aims to systematically review the therapeutic efficacy and safety of BTX-A in trigeminal neuralgia. PubMed, EMBASE, Cochrane Library Clinical Trials and Web of Science from January 1966 to March 2013 were searched with the terms of "botulinum toxin" AND "trigeminal neuralgia", and references of related articles were traced. Data on the efficacy and safety of BTX-A in this disorder were extracted and analyzed by at least 2 reviewers. Data for individual studies were reported, and pooled data were analyzed if appropriate. Five prospective studies and one double-blind, randomized, placebo-controlled study were identified. Response was achieved in approximately 70-100% of patients, and the mean pain intensity and frequency were reduced by approximately 60-100% at 4 weeks after treatment in most studies. Major adverse events were not reported. Available studies show BTX-A may be effective in treatment of trigeminal neuralgia. However, well-designed randomized, controlled, double-blinded trial is still lacking. Future BTX-A treatment studies on optimal dose, duration of the therapeutic efficacy, common AEs, and the time and indications for repeat injection would be promising.

The two different effects of the potential neuroprotective compound minocycline on AMPA-type glutamate receptors.

BACKGROUND: Minocycline has demonstrated neuroprotective effects in experimental neurodegenerative diseases. The aim of this study was to investigate if there is any direct interaction between minocycline and the AMPA-type receptor channels, and to elucidate the underlying molecular pharmacological mechanisms. METHODS: The patch-clamp technique was used combined with an ultrafast solution exchange system to investigate the interaction of minocycline with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y). RESULTS: Dose-dependent decreases in the relative peak current amplitude (rAmp) and the relative steady-state current (rC(des)) were found in coapplication experiments with GluR2L504Y receptors, but not in preincubation experiments. Furthermore, coapplication of 1 or 3 mmol/l minocycline showed a decrease in the fast time constant of current decay, and reopening currents were observed. But in the test with GluR2flipGQ receptors, rAmp, relative area under the curve and rC(des) increased with increasing concentrations of minocycline, and the steady-state time constant also increased when 3 µmol/l glutamate were used as agonist. CONCLUSION: Minocycline modulates AMPA-type receptor channels in a combination of a weaker open-channel block effect and a stronger potentiation effect, and the latter effect arises mainly from attenuating the extent of receptor desensitization.

Brain-Computer Interface-Robot Training Enhances Upper Extremity Performance and Changes the Cortical Activation in Stroke Patients: A Functional Near-Infrared Spectroscopy Study.

Introduction: We evaluated the efficacy of brain-computer interface (BCI) training to explore the hypothesized beneficial effects of physiotherapy alone in chronic stroke patients with moderate or severe paresis. We also focused on the neuroplastic changes in the primary motor cortex (M1) after BCI training. Methods: In this study, 18 hospitalized chronic stroke patients with moderate or severe motor deficits participated. Patients were operated on for 20 sessions and followed up after 1 month. Functional assessments were performed at five points, namely, pre1-, pre2-, mid-, post-training, and 1-month follow-up. Wolf Motor Function Test (WMFT) was used as the primary outcome measure, while Fugl-Meyer Assessment (FMA), its wrist and hand (FMA-WH) sub-score and its shoulder and elbow (FMA-SE) sub-score served as secondary outcome measures. Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) at baseline and after 20 sessions of BCI training. Pearson correlation analysis was used to evaluate functional connectivity (FC) across time points. Results: Compared to the baseline, better functional outcome was observed after BCI training and 1-month follow-up, including a significantly higher probability of achieving a clinically relevant increase in the WMFT full score (ΔWMFT score = 12.39 points, F = 30.28, and P < 0.001), WMFT completion time (ΔWMFT time = 248.39 s, F = 16.83, and P < 0.001), and FMA full score (ΔFMA-UE = 12.72 points, F = 106.07, and P < 0.001), FMA-WH sub-score (ΔFMA-WH = 5.6 points, F = 35.53, and P < 0.001), and FMA-SE sub-score (ΔFMA-SE = 8.06 points, F = 22.38, and P < 0.001). Compared to the baseline, after BCI training the FC between the ipsilateral M1 and the contralateral M1 was increased (P < 0.05), which was the same as the FC between the ipsilateral M1 and the ipsilateral frontal lobe, and the FC between the contralateral M1 and the contralateral frontal lobe was also increased (P < 0.05). Conclusion: The findings demonstrate that BCI-based rehabilitation could be an effective intervention for the motor performance of patients after stroke with moderate or severe upper limb paresis and represents a potential strategy in stroke neurorehabilitation. Our results suggest that FC between ipsilesional M1 and frontal cortex might be enhanced after BCI training. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2100046301.

Clinical scoring model based on age, NIHSS, and stroke-history predicts outcome 3 months after acute ischemic stroke.

Background: The clinical nomogram is a popular decision-making tool that can be used to predict patient outcomes, bringing benefits to clinicians and patients in clinical decision-making. This study established a simple and effective clinical prediction model to predict the 3-month prognosis of acute ischemic stroke (AIS), and based on the predicted results, improved clinical decision-making and improved patient outcomes. Methods: From 18 December 2021 to 8 January 2022, a total of 146 hospitalized patients with AIS confirmed by brain MR were collected, of which 132 eligible participants constituted a prospective study cohort. The least absolute shrinkage and selection operator (LASSO) regression was applied to a nomogram model development dataset to select features associated with poor prognosis in AIS for inclusion in the logistic regression of our risk scoring system. On this basis, the nomogram was drawn, evaluated for discriminative power, calibration, and clinical benefit, and validated internally by bootstrap. Finally, the optimal cutoff point for each independent risk factor and nomogram was calculated using the Youden index. Results: A total of 132 patients were included in this study, including 85 men and 47 women. Good outcome was found in 94 (71.212%) patients and bad outcome in 38 (28.788%) patients during the follow-up period. A total of eight (6.061%) deaths were reported over this period, of whom five (3.788%) died during hospitalization. Five factors affecting the 3-month prognosis of AIS were screened by LASSO regression, namely, age, hospital stay, previous stroke, atrial fibrillation, and NIHSS. Further multivariate logistic regression revealed three independent risk factors affecting patient outcomes, namely, age, previous stroke, and NIHSS. The area under the curve of the nomogram was 0.880, and the 95% confidence interval was 0.818-0.943, suggesting that the nomogram model has good discriminative power. The p-value for the calibration curve is 0.925, indicating that the nomogram model is well-calibrated. According to the decision curve analysis results, when the threshold probability is >0.01, the net benefit obtained by the nomogram is the largest. The concordance index for 1,000 bootstrapping calculations is 0.869. The age cutoff for predicting poor patient outcomes using the Youden index was 76.5 years (specificity 0.777 and sensitivity 0.684), the cutoff for the NIHSS was 7.5 (specificity 0.936, sensitivity 0.421), and the cutoff for total nomogram score was 68.8 (sensitivity 81.6% and specificity 79.8%). Conclusion: The nomogram model established in this study had good discrimination, calibration, and clinical benefits. A nomogram composed of age, previous stroke, and NIHSS might predict the prognosis of stroke after AIS. It might intuitively and individually predict the risk of poor prognosis in 3 months of AIS and provide a reference basis for screening the treatment plan of patients.

Changes of T lymphocyte subpopulations and their roles in predicting the risk of Parkinson's disease.

T lymphocytes are involved in the pathogenesis of Parkinson's disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8+ T cells (CD3+ CD8+ CD45RA+ CD45RO-) and increased late-differentiated CD4+ T cells (CD3+ CD4+ CD28- CD27-), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8+ T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4+ T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8+ T cells and late-differentiated CD4+ T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4+ T cells as candidates for multicentric clinical study and pathomechanism study of PD.

Dynamic muscle paralytic effects of a novel botulinum toxin A free of neurotoxin-associated proteins.

Structurally, botulinum toxin type A (BTX-A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX-As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time-to-peak paralytic effect of other BTX-As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX-As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin-eosin staining was performed. In conclusion, compared with other BTX-As, A/Chin showed rapid and steady time-to-peak paralytic effect and long-term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.

Comparative analysis of sensitivity and specificity of computer-aided cognitive test in screening mild cognitive impairment patients and test of reliability and validity.

OBJECTIVES: To evaluate the reliability and validity of the computer-aided cognitive test (CACT). METHODS: 219 Subjects of Tongji Hospital's Brain Health cohort (115 cases of Mild Cognitive Impairment (MCI) patients and 104 cases of normal controls) were enrolled, of which 24 cases received a retest after 2 weeks. Finally, the reliability and validity of the scale were tested and analyzed. RESULTS: (1) Reliability: (a) the internal consistency reliability of the total score of the scale was 0.645; (b) the retest reliability correlation coefficient of the total score of the scale was 0.900; (c) the Guttman Split-Half coefficient was 0.631; (2) Validity: (a) construct validity analysis showed that the correlation coefficient between each section score was between 0.036 and 0.408, and the correlation coefficient between each section score and the total score was between 0.468 and 0.781; (b) criterion validity analysis showed that the correlation coefficient between the total score of CACT and that of the Mini Mental State Examination (MMSE) was 0.733, and the coefficient between the total score of CACT and that of the basic version of the Montreal Cognitive Assessment (MoCA) was 0.763; (c) the area under the ROC curve of the CACT to distinguish between MCI patients and controls was 0.920, with an optimal diagnostic threshold of 20, a sensitivity of 88.5%, and a specificity of 80.9%. CONCLUSION: The CACT is little influenced by education level. It has good reliability and validity, which can be used for early clinical screening of cognitive dysfunction.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).