Therapeutic robots for post-stroke rehabilitation.

Stroke is a prevalent, severe, and disabling health-care issue on a global scale, inevitably leading to motor and cognitive deficits. It has become one of the most significant challenges in China, resulting in substantial social and economic burdens. In addition to the medication and surgical interventions during the acute phase, rehabilitation treatment plays a crucial role in stroke care. Robotic technology takes distinct advantages over traditional physical therapy, occupational therapy, and speech therapy, and is increasingly gaining popularity in post-stroke rehabilitation. The use of rehabilitation robots not only alleviates the workload of healthcare professionals but also enhances the prognosis for specific stroke patients. This review presents a concise overview of the application of therapeutic robots in post-stroke rehabilitation, with particular emphasis on the recovery of motor and cognitive function.

Kinect-based objective assessment of the acute levodopa challenge test in parkinsonism: a feasibility study.

INTRODUCTION: The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. METHODS: Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. RESULTS: The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features for arising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. CONCLUSION: This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.

Early-onset and late-onset Parkinson's disease exhibit a different profile of gait and posture features based on the Kinect.

INTRODUCTION: Gait and posture abnormalities are the common disabling motor symptoms in Parkinson's disease (PD). This study aims to investigate the differential characteristics of gait and posture in early-onset PD (EOPD) and late-onset PD (LOPD) using the Kinect depth camera. METHODS: Eighty-eight participants, including two subgroups of 22 PD patients and two subgroups of 22 healthy controls (HC) matched for age, sex, and height, were enrolled. Gait and posture features were quantitatively assessed using a Kinect-based system. A two-way analysis of variance was used to compare the difference between different subgroups. RESULTS: EOPD had a significantly higher Gait score than LOPD (p = 0.031). Specifically, decreased swing phase (p = 0.034) was observed in the EOPD group. Although the Posture score was similar between the two groups, LOPD was characterized by an increased forward flexion angle of the trunk at the thorax (p = 0.042) and a decreased forward flexion angle of the head relative to the trunk (p = 0.009). Additionally, age-independent features were observed in both PD subgroups, and post hoc tests revealed that EOPD generally performed worse gait features. In comparison, LOPD was characterized by worse performance in posture features. CONCLUSIONS: EOPD and LOPD exhibit different profiles of gait and posture features. The phenotype-specific characteristics likely reflect the distinct neurodegenerative processes between them.

Kinect-based objective assessment for early frailty identification in patients with Parkinson's disease.

BACKGROUND: Frailty is common in Parkinson's disease (PD) and increases vulnerability to adverse outcomes. Early detection of this syndrome aids in early intervention. AIMS: To objectively identify frailty at an early stage during routine motor tasks in PD patients using a Kinect-based system. METHODS: PD patients were recruited and assessed with the Fried criteria to determine their frailty status. Each participant was recorded performing the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) extremity tasks with a Kinect-based system. Statistically significant kinematic parameters were selected to discriminate the pre-frail from the non-frail group. RESULTS: Of the fifty-two participants, twenty were non-frail and thirty-two were pre-frail. Decreased frequency in finger tapping (P = 0.005), hand grasping (P = 0.002), toe tapping (P = 0.002), and leg agility (P = 0.019) alongside reduced hand grasping speed (P = 0.030), lifting (P < 0.001) and falling speed (P < 0.001) in leg agility were observed in the pre-frail group. Amplitude in leg agility (P = 0.048) and amplitude decrement rate (P = 0.046) in hand grasping showed marginally significant differences between two groups. Moderate discriminative values were found in frequency and speed of the extremity tasks to identify pre-frailty with sensitivity, specificity, and area under the curve (AUC) in the range of 45.00-85.00%, 68.75-100%, and 0.701-0.836, respectively. The combination of frequency and speed in extremity tasks showed moderate to high discriminatory ability, with AUC of 0.775 (95% CI 0.637-0.913, P < 0.001) for upper limb tasks and 0.909 (95% CI 0.832-0.987, P < 0.001) for lower limb tasks. When combining these features in both upper and lower limb tasks, the AUC increased to 0.942 (95% CI 0.886-0.999, P < 0.001). CONCLUSIONS: Our findings demonstrated the promise of utilizing Kinect-based kinematic data from MDS-UPDRS III tasks as early indicators of frailty in PD patients.

Kinect-based objective evaluation of bradykinesia in patients with Parkinson's disease.

Objective: To quantify bradykinesia in Parkinson's disease (PD) with a Kinect depth camera-based motion analysis system and to compare PD and healthy control (HC) subjects. Methods: Fifty PD patients and twenty-five HCs were recruited. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was used to evaluate the motor symptoms of PD. Kinematic features of five bradykinesia-related motor tasks were collected using Kinect depth camera. Then, kinematic features were correlated with the clinical scales and compared between groups. Results: Significant correlations were found between kinematic features and clinical scales (P < 0.05). Compared with HCs, PD patients exhibited a significant decrease in the frequency of finger tapping (P < 0.001), hand movement (P < 0.001), hand pronation-supination movements (P = 0.005), and leg agility (P = 0.003). Meanwhile, PD patients had a significant decrease in the speed of hand movements (P = 0.003) and toe tapping (P < 0.001) compared with HCs. Several kinematic features exhibited potential diagnostic value in distinguishing PD from HCs with area under the curve (AUC) ranging from 0.684-0.894 (P < 0.05). Furthermore, the combination of motor tasks exhibited the best diagnostic value with the highest AUC of 0.955 (95% CI = 0.913-0.997, P < 0.001). Conclusion: The Kinect-based motion analysis system can be applied to evaluate bradykinesia in PD. Kinematic features can be used to differentiate PD patients from HCs and combining kinematic features from different motor tasks can significantly improve the diagnostic value.

Technology-based therapy-response evaluation of axial motor symptoms under daily drug regimen of patients with Parkinson's disease.

Background: Axial disturbances are the most disabling symptoms of Parkinson's disease (PD). Kinect-based objective measures could extract motion characteristics with high reliability and validity. Purpose: The present research aimed to quantify the therapy-response of axial motor symptoms to daily medication regimen and to explore the correlates of the improvement rate (IR) of axial motor symptoms based on a Kinect camera. Materials and methods: We enrolled 44 patients with PD and 21 healthy controls. All 65 participants performed the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III and the Kinect-based kinematic evaluation to assess arising from a chair, gait, posture, and postural stability before and after medication. Spearman's correlation analysis and multiple linear regression model were performed to explore the relationships between motor feature IR and clinical data. Results: All the features arising from a chair (P = 0.001), stride length (P = 0.001), velocity (P < 0.001), the height of foot lift (P < 0.001), and turning time (P = 0.001) improved significantly after a daily drug regimen in patients with PD. In addition, the anterior trunk flexion (lumbar level) exhibited significant improvement (P = 0.004). The IR of the axial motor symptoms score was significantly correlated with the IRs of kinematic features for gait velocity, stride length, foot lift height, and sitting speed (r s = 0.345, P = 0.022; r s = 0.382, P = 0.010; r s = 0.314, P = 0.038; r s = 0.518, P < 0.001, respectively). A multivariable regression analysis showed that the improvement in axial motor symptoms was associated with the IR of gait velocity only (ß = 0.593, 95% CI = 0.023-1.164, P = 0.042). Conclusion: Axial symptoms were not completely drug-resistant, and some kinematic features can be improved after the daily medication regimen of patients with PD.

A summary index derived from Kinect to evaluate postural abnormalities severity in Parkinson's Disease patients.

Postural abnormalities are common disabling motor complications affecting patients with Parkinson's disease (PD). We proposed a summary index for postural abnormalities (IPA) based on Kinect depth camera and explored the clinical value of this indicator. Seventy individuals with PD and thirty age-matched healthy controls (HCs) were enrolled. All participants were tested using a Kinect-based system with IPA automatically obtained by algorithms. Significant correlations were detected between IPA and the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (rs = 0.369, p = 0.002), MDS-UPDRS-III total score (rs = 0.431, p < 0.001), MDS-UPDRS-III 3.13 score (rs = 0.573, p < 0.001), MDS-UPDRS-III-bradykinesia score (rs = 0.311, p = 0.010), the 39-item Parkinson's Disease Questionnaire (PDQ-39) (rs = 0.272, p = 0.0027) and the Berg Balance Scale (BBS) score (rs = -0.350, p = 0.006). The optimal cut-off value of IPA for distinguishing PD from HCs was 12.96 with a sensitivity of 97.14%, specificity of 100.00%, area under the curve (AUC) of 0.999 (0.997-1.002, p < 0.001), and adjusted AUC of 0.998 (0.993-1.000, p < 0.001). The optimal cut-off value of IPA for distinguishing between PD with and without postural abnormalities was 20.14 with a sensitivity, specificity, AUC and adjusted AUC of 77.78%, 73.53%, 0.817 (0.720-0.914, p < 0.001), and 0.783 (0.631-0.900, p < 0.001), respectively. IPA was significantly correlated to the clinical manifestations of PD patients, and could reflect the global severity of postural abnormalities in PD with important value in distinguishing PD from HCs and distinguishing PD with postural abnormalities from those without.

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.

High clinical diagnostic accuracy of combined salivary gland and myocardial metaiodobenzylguanidine scintigraphy in the diagnosis of Parkinson's disease.

Background: Decreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson's disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well. Purpose: To evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD). Methods: Thirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios. Results: The combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively. Conclusion: 131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.

Automated and accurate assessment for postural abnormalities in patients with Parkinson's disease based on Kinect and machine learning.

BACKGROUND: Automated and accurate assessment for postural abnormalities is necessary to monitor the clinical progress of Parkinson's disease (PD). The combination of depth camera and machine learning makes this purpose possible. METHODS: Kinect was used to collect the postural images from 70 PD patients. The collected images were processed to extract three-dimensional body joints, which were then converted to two-dimensional body joints to obtain eight quantified coronal and sagittal features (F1-F8) of the trunk. The decision tree classifier was carried out over a data set established by the collected features and the corresponding doctors' MDS-UPDRS-III 3.13 (the 13th item of the third part of Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) scores. An objective function was implanted to further improve the human-machine consistency. RESULTS: The automated grading of postural abnormalities for PD patients was realized with only six selected features. The intraclass correlation coefficient (ICC) between the machine's and doctors' score was 0.940 (95%CI, 0.905-0.962), meaning the machine was highly consistent with the doctors' judgement. Besides, the decision tree classifier performed outstandingly, reaching 90.0% of accuracy, 95.7% of specificity and 89.1% of sensitivity in rating postural severity. CONCLUSIONS: We developed an intelligent evaluation system to provide accurate and automated assessment of trunk postural abnormalities in PD patients. This study demonstrates the practicability of our proposed method in the clinical scenario to help making the medical decision about PD.

A Stable Cell Line Expressing Clustered AChR: A Novel Cell-Based Assay for Anti-AChR Antibody Detection in Myasthenia Gravis.

Cell-based assays (CBAs) and radioimmunoprecipitation assay (RIPA) are the most sensitive methods for identifying anti-acetylcholine receptor (AChR) antibody in myasthenia gravis (MG). But CBAs are limited in clinical practice by transient transfection. We established a stable cell line (KL525) expressing clustered AChR by infecting HEK 293T cells with dual lentiviral vectors expressing the genes encoding the human AChR α1, ß1, δ, ϵ and the clustering protein rapsyn. We verified the stable expression of human clustered AChR by immunofluorescence, immunoblotting, and real-time PCR. Fluorescence-activated cell sorting (FACS) was used to detect anti-AChR antibodies in 103 MG patients and 58 healthy individuals. The positive results of MG patients reported by the KL525 was 80.6% (83/103), 29.1% higher than the 51.4% (53/103) of RIPA. 58 healthy individuals tested by both the KL525 CBA and RIPA were all negative. In summary, the stable expression of clustered AChR in our cell line makes it highly sensitive and advantageous for broad clinical application in CBAs.

Association Between Low-Density Lipoprotein Cholesterol and Platelet Distribution Width in Acute Ischemic Stroke.

Objective: Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for ischemic stroke; however, whether LDL-C affects the platelet deformation function in the peripheral blood circulation in patients with acute ischemic stroke (AIS) is unknown. The present study aimed to investigate the relationship between LDL-C and platelet distribution width (PDW) in AIS patients. Methods: We conducted a cross-sectional hospitalized-based study of consecutive 438 patients with AIS within 24 h. Blood samples were collected upon admission and prior to drug administration, and LDL-C and PDW (a parameter that reflects the heterogeneity of platelet volume) were assessed. The relationship between LDL-C and PDW were analyzed by linear curve fitting analyses. Crude and adjusted beta coefficients of LDL-C for PDW with 95% confidence intervals were analyzed using multivariate-adjusted linear regression models. Results: The PDW was significantly higher in the high LDL-C group compared with those in the normal LDL-C group (16.28 ± 0.37 fl vs. 16.08 ± 0.37 fl, p < 0.001). Adjusted smoothed plots suggested that there are linear relationships between LDL-C and PDW, and the Pearson's correlation coefficient (95%) was 0.387 (0.304-0.464, p < 0.001). The beta coefficients (95% CI) between LDL-C and PDW were 0.15 (0.12-0.18, p < 0.001) and 0.14 (0.11-0.18, p < 0.001), respectively, in AIS patients before and after adjusting for potential confounders. Conclusion: Our study suggested that the elevated LDL-C level was related to increased PDW among AIS patients.

TRIM27-mediated ubiquitination of PPARγ promotes glutamate-induced cell apoptosis and inflammation.

Neurotoxicity induced by glutamate (Glu) is often used to study the signaling mechanism of neurological disorders. The identification of specific genetic factors that cause Glu-induced neurotoxicity provides evidence for the common pathways of neuronal apoptosis and inflammation. TRIM27 has been found to induce apoptosis and inflammation. Nevertheless, there is little evidence that TRIM27 is associated with Glu-induced neurotoxicity. We found that TRIM27 expression was increased in epilepsy patients and in HT22 cells following Glu treatment. Glu-mediated cell apoptosis, decreased PPARγ expression, and increased levels of cleaved Caspase-3 and IL-1ß expression in HT22 cells were significantly inhibited by TRIM27 knockdown. TRIM27 overexpression significantly induced cell apoptosis and expression of cleaved Caspase-3 and IL-1ß, but inhibited PPARγ expression in HT22 cells, which were reversed by ROZ, suggesting the involvement of PPARγ in TRIM27-mediated cell apoptosis and inflammation in HT22 cells. Mechanically, TRIM27 ubiquitinates and degrades PPARγ, following induces cleaved Caspase-3 and IL-1ß expression. Clinically, increased expression of TRIM27 in epilepsy patients was associated with decreased PPARγ expression. Taken together, our study suggests that TRIM27-mediated ubiquitination of PPARγ promotes Glu-induced HT22 cell apoptosis and IL-1ß release.

Red blood cell distribution width is associated with neuronal damage in acute ischemic stroke.

Elevated red blood cell distribution width (RDW) has been found to be associated with the occurrence of ischemic stroke. However, there is no defined relationship between RDW and neuronal damage in acute ischemic stroke (AIS). This study was designed to determine the relationship between RDW and neuronal damage in AIS patients. A total of 442 consecutive AIS patients from January 2018 to June 2019 were evaluated for neuronal damage, which was estimated by serum neuron-specific enolase (NSE) levels. Red blood cell distribution width-standard deviation (RDW-SD), a parameter that reflects the heterogeneity of red blood cell volume, was also assessed. We evaluated the association between the RDW-SD and serum NSE level through multivariate-adjusted linear regression analysis. Both the serum NSE level and the incidence of high NSE increased according to the increased RDW-SD tertile in AIS patients (p<0.01). There was a positive correlation between RDW-SD and serum NSE levels (r=0.275, 95% CI: 0.187-0.359, p<0.001). The beta coefficients (95% CI) between RDW-SD and serum NSE levels were 0.32 (0.21-0.42, p<0.001) and 0.26 (0.15-0.38, p<0.001), respectively, in AIS patients before and after adjusting for potential confounders. In conclusion, we found a significant positive association between RDW-SD and neuronal damage in AIS patients.

Serum albumin level is associated with the severity of neurological dysfunction of NMOSD patients.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system. Serum albumin (SA) has antioxidant, immunomodulatory and anti-inflammatory effects. However, the roles of SA in NMOSD have not been studied. The current study aimed to clarify the association of SA with disease severity and prognosis in NMOSD patients. METHODS: Serum levels of albumin were measured by Bromcresol Green method. Serum level measurements of interleukins were performed using enzyme-linked immunoassay (ELISA) method. RESULTS: Of all the 130 NMOSD patients, 96 patients were in the acute phase while 34 patients were in the remission phase of disease at the time of sampling. SA concentration was significantly correlated with EDSS score in patients in the acute phase but not in remission phase (r = - 0.388, p < 0.001 and r = - 0.467, p = 0.809, respectively). Logistic analysis revealed that SA was the only significant factor to predict severe NMOSD (EDSS 8.0-9.5) OR = 0.698, 95%CI 0.563-0.865, p = 0.001) after adjustment of other confounding factors. Furthermore, SA was negatively correlated with the serum level of IL-33 (r = -0.438, p = 0.016) in the acute phase of NMOSD patients. CONCLUSION: The current study found that low level of SA was an independent indicator of more severe neurological deficit in patients in acute phase of NMOSD. SA concentration was negatively correlated with the serum level of IL-33 in the acute phase of the disease, which implies that SA might participate in the immunopathology of NMOSD partly through its interaction with IL-33.

Lower serum interleukin-22 and interleukin-35 levels are associated with disease status in neuromyelitis optica spectrum disorders.

AIMS: The exact pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) remains unclear. A variety of cytokines are involved, but few studies have been performed to explore the novel roles of interleukin-22 (IL-22) and interleukin-35 (IL-35) in NMOSD. Therefore, this study was designed to investigate serum levels of IL-22 and IL-35, and their correlations with clinical and laboratory characteristics in NMOSD. METHODS: We performed a cross-section study, 18 patients with acute NMOSD, 23 patients with remission NMOSD, and 36 healthy controls were consecutively enrolled. Serum levels of IL-22 and IL-35 were measured by enzyme-linked immunosorbent assay (ELISA). The correlations between serum IL-22 and IL-35 levels and clinical and laboratory characteristics were evaluated by Spearman's rank or Pearson's correlation coefficient. RESULTS: The serum levels of IL-22 and IL-35 were significantly lower in patients with acute NMOSD and remission NMOSD than in healthy controls (IL-22: 76.96 ± 13.62 pg/mL, 87.30 ± 12.79 pg/mL, and 94.02 ± 8.52 pg/mL, respectively, P < .0001; IL-35: 45.52 ± 7.04 pg/mL, 57.07 ± 7.68 pg/mL, and 60.05 ± 20.181 pg/mL, respectively, P < .0001). Serum levels of IL-35 were negatively correlated with EDSS scores and cerebrospinal fluid protein levels (r = -.5438, P = .0002 and r = -.3523, P = .0258, respectively) in all patients. CONCLUSIONS: Lower serum levels of IL-22 and IL-35 are associated with disease status in NMOSD. Additionally, lower serum levels of IL-35 are associated with disease severity in NMOSD.

The differential expression of natural killer cells in NMOSD and MS.

Natural killer (NK) cells are involved in the pathogenesis of inflammatory demyelinating diseases of the central nervous system. However, the differential expressions of NK cells in the peripheral blood of patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are unknown. This study aimed to explore the differential expressions of NK cells in NMOSD and MS and evaluate the clinical implications of this difference. We performed a cross-sectional study to investigate the expression of NK cells in the peripheral blood of patients with NMOSD (n = 78) and MS (n = 24) and of healthy controls (HC, n = 27). Furthermore, we investigated the relationship between NK cell level and disease phase in 102 patients with NMOSD and MS through Spearman correlation analysis and receiver operating characteristic (ROC) analysis. Our results showed that the median (interquartile range) NK cell levels in acute-phase NMOSD patients, remission-phase NMOSD patients, acute-phase MS patients, and HC subjects were 114.10 (64.75-153.38) cells/µL, 167.60 (116.35-266.15) cells/µL, 282.55 (140.57-368.20) cells/µL, and 221.00 (170.40-269.55) cells/µL, respectively (p < 0.001). The Spearman correlation coefficient (95%) for the relationship between NK level and disease phase in NMOSD patients was 0.366 (0.150-0.550) (p < 0.001). Furthermore, ROC analysis revealed that patients with NK cell values lower than 172.200 cells/µL were more prone to have acute-phase NMOSD than MS. In conclusion, the expression of NK cells in peripheral blood was lower in patients with NMOSD than in patients with MS in the acute phase, and a low expression of NK cells may suggest having acute-phase NMOSD rather than MS.

Increased interleukin-18 level contributes to the development and severity of ischemic stroke.

Although interleukin-18 (IL-18) has been implicated in the pathophysiology of stroke, research findings concerning IL-18 level in stroke have been inconsistent. Thus, we performed a cross-sectional study in patients with first-episode ischemic stroke and then extracted relevant data from databases to validate our results. A total of 252 patients and 259 healthy subjects were recruited, and serum IL-18 level was evaluated in a cross-sectional study. Then, we extracted data and conducted a meta-analysis, including 2,928 patients and 3,739 controls to support our results. A 95% confidence interval for standardized mean difference (SMD) was calculated using a Z test. We found IL-18 was higher in stroke patients than in controls (2.39 ± 0.25 vs. 2.25 ± 0.28, F=8.60, p=0.004) and was negatively associated with the NIHSS scale (r = -0.14, p=0.028). A subsequent meta-analysis confirmed that IL-18 level was higher in stroke patients than in controls (SMD = 2.14, 95% CI = 1.54 ∼ 2.73, P< 0.001). IL-18 level increased with the severity of the stroke (p< 0.01). These findings revealed increased IL-18 level contributed to the development and severity of ischemic stroke, suggesting the potential of this biomarker to become an important reference for the early monitoring of ischemic stroke.

Puerarin alleviates streptozotocin (STZ)-induced osteoporosis in rats through suppressing inflammation and apoptosis via HDAC1/HDAC3 signaling.

Diabetic osteoporosis is a severe public health concern in the world. Puerarin (PU) is extensively attractive due to its superior bioactivities. In the study, we found that PU protected against streptozotocin (STZ)-induced osteoporotic changes in rats. PU treatment improved STZ-induced diabetes in rats, as evidenced by the reduced serum glucose and insulin levels. PU administration markedly attenuated bone loss and tartarate-resistant acid phosphatase (TRAP) activity in STZ-induced rats. Bone mineral density (BMD) was significantly decreased in diabetic rats, while being prevented by PU. STZ-induced impairments in microarchitecture of femoral tissues were markedly alleviated by PU treatment. In addition, bone-specific alkaline phosphatase (BALP), osteoprotegerin (OPG) and Runt-related transcription factor 2 (Runx2) levels in serum or tibia were improved by PU in STZ-injected rats; however, TRACP isoform 5b (TRACP-5b), carboxy-terminal collagen cross-links (ß-CTX) and receptor activator of nuclear factor-κB ligand (RANKL) levels were decreased. Further, PU treatment inhibited inflammation and apoptosis in STZ-treated rats. Additionally, STZ injection increased histone deacetylase (HDAC)-1 and -3 expressions in femoral heads of rats, which were relieved by PU treatment. Notably, both HDAC1 and HDAC3 could enhance osteoporosis in vitro, as proved by the decreased ALP and Runx2 levels and the increased TRAP expression. Inflammation and apoptosis were exacerbated by HDAC1/3 over-expression, which were markedly diminished by PU treatment. In contrast, suppressing HDAC1/3 significantly abrogated fructose (Fru)-elicited inflammation and apoptosis in cells. Collectively, our data illustrated that PU is a potential therapeutic option to prevent diabetic osteoporosis by inhibiting HDAC1/HDAC3 signaling.

Identification of association between rs1057317 polymorphism in TLR4 3'-untranslated region and the susceptibility to osteoporosis.

It has been proved that the expression of TLR4 is associated with a reduced risk of osteoporosis (OP). One single-nucleotide polymorphism located within the 3'-untranslated region (3'-UTR) of TLR4 may "generate" binding site of miR-34a and thereby associated with risk of OP. Bioinformatics analysis and luciferase reporter assay were used to specify the effect of polymorphisms on the interaction between miR-34a and TLR4 gene. Western blot analysis and real-time polymerase chain reaction were used to study the expressions of miR-34a, TLR4 in different groups or cells transfected with miR-34a mimics or inhibitor. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to estimate the effect of miR-34a on the apoptosis of osteoblast. TLR4 was identified as a target of miR-34a, with negative regulatory relationship predicted. The expression levels of miR-34a was comparable with each other between CC, CA, and AA groups, and the expression levels of TLR4 was evidently lower in CC compared with GG and GC groups. Also, TLR4 level in culture osteoblast (genotyped as CC) treated with miR-34a mimics was substantially downregulated compared with scramble control, while those cells (genotyped as CC) treated with miR-34a inhibitors showed increased expression of TLR4. Additionally, the apoptosis of osteoblast genotyped as CC was decreased following transfection with miR-34a mimics, while evidently promoted subsequent to transfect with miR-34a inhibitor. The regulatory association between rs1057317 polymorphism in TLR4 3'-UTR led to an inhibitory effect on the expression of TLR4 by miR-34a, which may explain the observed association between the polymorphism and the susceptibility to OP.