Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Subthalamic nucleus-deep brain stimulation improves autonomic dysfunctions in Parkinson's disease.

BACKGROUND: To study the effects of subthalamic nucleus-deep brain stimulation (STN-DBS) on autonomic dysfunctions in Parkinson's disease (PD) patients. METHODS: A total of 57 PD patients who underwent bilateral STN-DBS from March to December 2018, were retrospectively analyzed. Preplanned assessments at baseline and postoperatively at 1, 3, and 6 months also included the Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-Aut), the Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39), the Hamilton Anxiety Rating Scale (HAMA), and the Hamilton Depression Rating Scale (HAMD). RESULTS: The SCOPA-Aut scores improved significantly [14.59% (18.32%), 24.00% (27.05%), 22.16% (27.07%), all P < 0.001] at 1 month, 3 months, and 6 months of STN-DBS, respectively. Analysis of the SCOPA-Aut sub-items showed significant improvements only in urine and thermoregulation sub-items at 6 months after surgery (P < 0.001). There was no significant correlation between improvements of SCOPA-Aut scores and improvements of PDQ-39 scores (P > 0.05) at 6 months after surgery. SCOPA-Aut scores were positively correlated with age (r = 0.428, P = 0.001); the improvements of SCCOPA-Aut scores were positively correlated with improvements of HAMA and HAMD scores (HAMA: r = 0.325, P = 0.015; HAMD: r = 0.265, P = 0.049) at 6 months after surgery. CONCLUSION: STN-DBS improved autonomic dysfunction symptoms of PD patients, and urinary and thermoregulatory sub-items of autonomic dysfunction were improved in the short-term after surgery. There was a close relationship between improved autonomic symptoms and improved anxiety and depression 6 months after surgery. We should therefore direct more attention to autonomic dysfunctions in PD involving detailed preoperative evaluations and postoperative follow-ups, to improve the quality of life of patients.

LncRNA H19 contributes to hippocampal glial cell activation via JAK/STAT signaling in a rat model of temporal lobe epilepsy.

BACKGROUND: Astrocyte and microglia activation are well-known features of temporal lobe epilepsy that may contribute to epileptogenesis. However, the mechanisms underlying glia activation are not well understood. Long non-coding RNA (lncRNA) H19 has diverse functions depending on physiological or pathological state, and its role in epilepsy is unknown. We previously demonstrated that H19 was significantly upregulated in the latent period of epilepsy and may be associated with cell proliferation and immune and inflammatory responses. We therefore speculated that H19 is involved in the hippocampal glial cell activation during epileptogenesis. METHODS: H19 was overexpressed or knocked down using an adeno-associated viral vector delivery system. A rat status epilepticus model was induced by intra-amygdala kainic acid injection. Astrocyte and microglia activation were assessed by immunofluorescence and western blot analyses. Expression of proinflammatory cytokines and components of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were evaluated with western blotting. RESULTS: H19 overexpression induced the activation of astrocytes and microglia and the release of proinflammatory cytokines (interleukin-1ß and interleukin-6 and tumor necrosis factor-α) in the hippocampus, whereas H19 knockdown inhibited status epilepticus-induced glial cell activation. Moreover, H19 activated JAK/STAT signaling by promoting the expression of Stat3 and c-Myc, which is thought to be involved in astrocyte activation. CONCLUSIONS: LncRNA H19 contributes to hippocampal glial cell activation via modulation of the JAK/STAT pathway and could be a therapeutic tool to prevent the development of epilepsy.

Abnormal hippocampal functional network and related memory impairment in pilocarpine-treated rats.

OBJECTIVE: Although abnormal hippocampal structure and impaired spatial memory have been revealed in a pilocarpine rat model of temporal lobe epilepsy (TLE), the brain functional network changes are still unclear. The aim of the present study was to investigate the changes of brain functional connectivity related to the hippocampus and the associated memory impairment in a pilocarpine model of TLE. METHODS: Functional magnetic resonance imaging signals were recorded in pilocarpine-treated rats and controls by using a 7.0 T magnetic resonance scanner, and independent component analysis was performed to determine the hippocampal functional network. Behavioral tests, including novel location test, novel object test, and episodic memory test, were utilized to evaluate different aspects of memory impairment. RESULTS: Memory impairment was observed in the TLE group in all three behavior tests. As compared to control, decreased connectivity of the hippocampal functional network was observed in the anterior dorsal hippocampus, the amygdala, the thalamus, the motor cortex, and the somatosensory cortex in the TLE group. Meanwhile, increased connectivity was found in the visual cortex, the mesencephalon, and the insula in the TLE group. Correlation analysis revealed that functional connections between the hippocampal network and brain regions such as the dorsal hippocampus and the thalamus specifically relate to the spatial memory behavior, whereas connections between the hippocampal network and regions such as the amygdala, the motor cortex, the somatosensory cortex, and the mesencephalon relate to both the spatial and the object memory performance. SIGNIFICANCE: Our results indicated a trend of decreased connectivity in the hippocampal functional network, as well as spatial, object, and episodic memory impairment in the pilocarpine-induced TLE rat. Moreover, connections within the hippocampal network showed a relationship with spatial memory, and connections between the hippocampal network and regions in other networks revealed an association with both spatial and object memory.

Whole-transcriptome screening reveals the regulatory targets and functions of long non-coding RNA H19 in epileptic rats.

Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown. In the present study, high-throughput microarray analysis was used to explore the influence of H19 on gene expression in an epileptic rat model. A large number of genes were differentially expressed at the transcriptional level when H19 was overexpressed or knocked down. Series test of cluster analysis further distinguished genes associated with H19. Function and pathway analyses demonstrated that H19 has diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis, and activation of MAPK. This study implicates H19 in a broad spectrum of epileptogenic processes, thereby providing a range of targets for further mechanistic investigations.

An Evaluation Analysis for Computed Tomography Image Quality of Primary Liver Cancer Lesions Based on Deep Learning Image Reconstruction.

BACKGROUND: Abdominal multi-slice helical computed tomography (CT) and contrast-enhanced scanning have been widely recognized clinically. OBJECTIVE: The impact of the deep learning image reconstruction (DLIR) on the quality of dynamic contrast-enhanced CT imaging of primary liver cancer lesions was evaluated through comparison with the filtered back projection (FBP) and the new generation of adaptive statistical iterative reconstruction-V (ASIR-V). METHODS: We evaluated the image noise of the lesion, fine structures inside the lesion, and diagnostic confidence in 48 liver cancer subjects. The CT values of the solid part of the lesion and the adjacent normal liver tissue and the systolic and diastolic blood pressure (SD) values of the right paravertebral muscle were measured. The muscle SD value was considered as the background noise of the image, and the signal noise ratio (SNR) and contrast signal-to-noise ratio (CNR) of the lesion and normal liver parenchyma were calculated. RESULTS: High consistency in the evaluation of image noise (Kappa = 0.717). The Kappa values for margin/pseudocapsule, fine structure within the lesion, and diagnostic confidence were 0.463, 0.527, and 0.625, respectively. Besides, the differences in SD, SNR and CNR data of reconstructed lesion images among the six groups were statistically significant. CONCLUSION: The contrast-enhanced CT image noise of DLIR-H in the portal venous phase is much lower than that of ASIR-V and FBP in primary liver cancer patients. In terms of the lesion structure display, the new reconstruction algorithm DLIR is superior.

Emotional symptoms and cognitive function outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts and the volume of tissue activated.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), that can improve patients' motor and non-motor symptoms. However, there are differences in the improvement of patients' emotional symptoms and cognitive function. OBJECTIVE: To investigate the impact of active contact location and the volume of tissue activated (VTA) on patients' emotional symptoms and cognitive function in STN-DBS in PD. METHODS: A total of 185 PD patients were included in this study. We evaluated them using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE) scales at the preoperative, 1- and 12-month postoperative time points. Leads were positioned in standard space using the Lead-DBS toolbox, and VTA was calculated for analysis. RESULTS: When the lead active contact was closer to the ventral side of the STN, the patients' HAM-A improvement rate was higher, and when the active contact was closer to the anterior and dorsal sides of the STN, the patients' MoCA improvement rate was higher. Stimulation of the sensorimotor zone was more favorable to the improvement of HAM-A and HAM-D in patients. And, the stimulation of the associative zone was more favorable to the improvement of MoCA in patients. CONCLUSION: Our results provide evidence that the 12-month outcomes of cognitive function and emotional symptoms in PD patients with STN-DBS were closely related to the specific location of the active contacts in the STN and influenced by the VTA.

Association between long-term green space exposure and mortality in China: A difference-in-differences analysis of national data in 2000, 2010 and 2019.

BACKGROUND: Effects of green space on human health have been well-documented in western, high-income countries. Evidence for similar effects in China is limited. Moreover, the underlying mechanisms linking green space and mortality are yet to be established. We therefore conducted a nation-wide study to assess the association between green space and mortality in China using a difference-in-difference approach, which applied a causal framework and well controlled unmeasured confounding. In addition, we explored whether air pollution and air temperature could mediate the association. METHODS: In this analysis, we collected data on all-cause mortality and sociodemographic characteristics for each county in China from the 2000 and 2010 censuses and the 2020 Statistical Yearbook. Green space exposure was assessed using county-level normalized difference vegetation index (NDVI) and the percentage of green space (forest, grasslands, shrub land and wetland). We applied a difference-in-differences approach to evaluate the association between green space and mortality. We also performed mediation analysis (by air pollution and air temperature). RESULTS: Our sample consisted of 2726 counties in 2000 and 2010 as well as 1432 counties in 2019. In the 2000 versus 2019 comparison, a 0.1 unit increase in NDVI was associated with a 2.4 % reduction in mortality [95 % confidence interval (CI) 0.4-4.3 %], and a 10 % increase in percentage of green space was associated with a 4.7 % reduction (95 % CI 0-9.2 %) in mortality. PM2.5 and air temperature mediated 0.3 % to 12.3 % of the associations. CONCLUSIONS: Living in greener counties may be associated with lower risk of mortality in China. These findings could indicate the potential of a population-level intervention to reduce mortality in China, which has important public health implications at the county level.

[Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats].

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

Correlation between Electrode Location and Anxiety Depression of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

Objectives: our group explored the correlation between postoperative coordinates of the electrode contacts, VTA, and anxiety and depression symptoms in Parkinson's disease (PD) patients after subthalamic nucleus deep brain stimulation (STN-DBS). Methods: STN-DBS was conducted on PD patients (n = 57) for six months with follow-up. Clinical outcomes were explored using the unified Parkinson's disease rating scale Part III (UPDRS-III), the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D) before and after surgery. At the Montreal Neurological Institute (MNI), the location of active contacts and the volume of tissue activated (VTA) were calculated. Results: patient evaluations took place preoperatively and follow-ups took place at 1 month, 3 months, and 6 months. The average patient improvement rates for HAM-A and HAM-D scores at the 6-month follow-up were 41.7% [interquartile range (IQR) 34.9%] and 37.5% (IQR 33.4%), respectively (both p < 0.001). In medication-off, there were negative correlations between the HAM-A improvement rate and the Z-axis coordinate of the active contact (left side: r = −0.308, p = 0.020; right side: r = −0.390, p = 0.003), and negative correlations between the HAM-D improvement rate and the Z-axis coordinate of the active contact (left side: r = −0.345, p = 0.009; right side: r = −0.521, p = 0.001). There were positive correlations between the HAM-A and HAM-D scores improvement rate at 6 months after surgery and bilateral VTA in the right STN limbic subregion (HAM-A: r = 0.314, p = 0.018; HAM-D: r = 0.321, p = 0.015). Conclusion: bilateral STN-DBS can improve anxiety and depression symptoms in PD patients. The closer the stimulation to the ventral limbic region of the STN, the more significant the improvement in anxiety and depression symptoms of PD patients.

Transcriptome Sequencing Reveal That Rno-Rsf1_0012 Participates in Levodopa-Induced Dyskinesia in Parkinson's Disease Rats via Binding to Rno-mir-298-5p.

Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson's disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop structure, which can regulate gene expression and participate in many biological processes. However, the biological roles of circRNAs in LID are not completely known. In the present study, we established typical LID rat models by unilateral lesions of the medial forebrain bundle and repeated levodopa therapy. High-throughput next-generation sequencing was used to screen circRNAs differentially expressed in the brain of LID and non-LID (NLID) rats, and key circRNAs were selected according to bioinformatics analyses. Regarding fold change ≥2 and p < 0.05 as the cutoff value, there were a total of 99 differential circRNAs, including 39 up-regulated and 60 down-regulated circRNAs between the NLID and LID groups. The expression of rno-Rsf1_0012 was significantly increased in the striatum of LID rats and competitively bound rno-mir-298-5p. The high expression of target genes PCP and TBP in LID rats also supports the conclusion that rno-Rsf1_0012 may be related to the occurrence of LID.

[Association of filaggrin gene polymorphism with atopic dermatitis in southern Chinese Han population].

OBJECTIVE: To investigate the association of filaggrin gene (FLG) polymorphism with atopic dermatitis (AD) in southern Chinese Han population. METHODS: The frequencies of the 13 known FLG gene single nucleotide polymorphism(SNPs), including 3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X, were detected in a cohort of 50 AD patients and 100 control individuals using polymerase chain reaction (PCR) and DNA sequencing. RESULTS: FLG 3321delA and 441delA were detected in 14 (28%) and 6 (12%) AD patients, respectively. The other 11 SNPs were not detected in the patients. None of the 13 SNPs was detected in the controls. CONCLUSION: The results suggested that the FLG gene might be associated with atopic dermatitis susceptibility in southern Chinese Han population.

Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy.

BACKGROUND: Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level. METHODS: We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. RESULTS: The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance. CONCLUSION: Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

The risk of shoulder pain after laparoscopic surgery for infertility is higher in thin patients.

Postlaparoscopic shoulder pain (PLSP) is a common clinical problem that needs to be addressed by medical professionals who are currently perform laparoscopic surgeries. The purpose of this study was to determine the perioperative clinical factors and demographic characteristics associated with PLSP. A prospective observational study was performed with 442 inpatients undergoing laparoscopic surgery for infertility. The pain visual analogue scale was used as the measuring instrument. To identify the predictors of PLSP, we performed multivariate conditional logistic regression. PLSP was correlated with body mass index (BMI, odds ratio = 0.815). The incidence of shoulder pain and more severe shoulder pain in patients with a lower BMI was significantly higher than it was in patients with a higher BMI, and BMI was significantly negatively correlated with PLSP. Most of the patients (95%) began to experience shoulder pain on the first postoperative day, and it rarely occurred on the day of surgery. Patients with lower BMI presented a higher risk of reporting shoulder pain on the first postoperative day. We should identify high-risk patients in advance and make specific treatment plans according to the characteristics of their symptoms.

Radiomics Analysis of Magnetic Resonance Imaging Facilitates the Identification of Preclinical Alzheimer's Disease: An Exploratory Study.

Diagnosing Alzheimer's disease (AD) in the preclinical stage offers opportunities for early intervention; however, there is currently a lack of convenient biomarkers to facilitate the diagnosis. Using radiomics analysis, we aimed to determine whether the features extracted from multiparametric magnetic resonance imaging (MRI) can be used as potential biomarkers. This study was part of the Sino Longitudinal Study on Cognitive Decline project (NCT03370744), a prospective cohort study. All participants were cognitively healthy at baseline. Cohort 1 (n = 183) was divided into individuals with preclinical AD (n = 78) and controls (n = 105) using amyloid-positron emission tomography, and this cohort was used as the training dataset (80%) and validation dataset (the remaining 20%); cohort 2 (n = 51) was selected retrospectively and divided into "converters" and "nonconverters" according to individuals' future cognitive status, and this cohort was used as a separate test dataset; cohort three included 37 converters (13 from the Alzheimer's Disease Neuroimaging Initiative) and was used as another test set for independent longitudinal research. We extracted radiomics features from multiparametric MRI scans from each participant, using t-tests, autocorrelation tests, and three independent selection algorithms. We then established two classification models (support vector machine [SVM] and random forest [RF]) to verify the efficiency of the retained features. Five-fold cross-validation and 100 repetitions were carried out for the above process. Furthermore, the acquired stable high-frequency features were tested in cohort three by paired two-sample t-tests and survival analyses to identify whether their levels changed with cognitive decline and impact conversion time. The SVM and RF models both showed excellent classification efficiency, with an average accuracy of 89.7-95.9% and 87.1-90.8% in the validation set and 81.9-89.1% and 83.2-83.7% in the test set, respectively. Three stable high-frequency features were identified, all based on the structural MRI modality: the large zone high-gray-level emphasis feature of the right posterior cingulate gyrus, the variance feature of the left superior parietal gyrus, and the coarseness feature of the left posterior cingulate gyrus; their levels were correlated with amyloid-ß deposition and predicted future cognitive decline (areas under the curve 0.649-0.761). In addition, levels of the variance feature at baseline decreased with cognitive decline and could affect the conversion time (p < 0.05). In conclusion, this exploratory study shows that the radiomics features of multiparametric MRI scans could represent potential biomarkers of preclinical AD.

The lncRNA H19 binding to let-7b promotes hippocampal glial cell activation and epileptic seizures by targeting Stat3 in a rat model of temporal lobe epilepsy.

OBJECTIVES: Glial cell activation contributes to the inflammatory response and occurrence of epilepsy. Our preliminary study demonstrated that the long non-coding RNA, H19, promotes hippocampal glial cell activation during epileptogenesis. However, the precise mechanisms underlying this effect remain unclear. MATERIALS AND METHODS: H19 and let-7b were overexpressed or silenced using an adeno-associated viral vector in vivo. Their expression in a kainic acid-induced epilepsy model was evaluated by real-time quantitative PCR, fluorescence in situ hybridization, and cytoplasmic and nuclear RNA isolation. A dual-luciferase reporter assay was used to evaluate the direct binding of let-7b to its target genes and H19. Western blot, video camera monitoring and Morris water maze were performed to confirm the role of H19 and let7b on epileptogenesis. RESULTS: H19 was increased in rat hippocampus neurons after status epilepticus, which might be due to epileptic seizure-induced hypoxia. Increased H19 aggravated the epileptic seizures, memory impairment and mossy fibre sprouting of the epileptic rats. H19 could competitively bind to let-7b to suppress its expression. Overexpression of let-7b inhibited hippocampal glial cell activation, inflammatory response and epileptic seizures by targeting Stat3. Moreover, overexpressed H19 reversed the inhibitory effect of let-7b on glial cell activation. CONCLUSIONS: LncRNA H19 could competitively bind to let-7b to promote hippocampal glial cell activation and epileptic seizures by targeting Stat3 in a rat model of temporal lobe epilepsy.

Electromyography Biomarkers for Quantifying the Intraoperative Efficacy of Deep Brain Stimulation in Parkinson's Patients With Resting Tremor.

Introduction: Deep brain stimulation (DBS) is an effective therapy for resting tremor in Parkinson's disease (PD). However, quick and objective biomarkers for quantifying the efficacy of DBS intraoperatively are lacking. Therefore, we aimed to study how DBS modulates the intraoperative neuromuscular pattern of resting tremor in PD patients and to find predictive surface electromyography (sEMG) biomarkers for quantifying the intraoperative efficacy of DBS. Methods: Intraoperative sEMG of 39 PD patients with resting tremor was measured with the DBS on and off, respectively, during the intraoperative DBS testing stage. Twelve signal features (time and frequency domains) were extracted from the intraoperative sEMG data. These sEMG features were associated with the clinical outcome to evaluate the efficacy of intraoperative DBS. Also, an sEMG-based prediction model was established to predict the clinical improvement rate (IR) of resting tremor with DBS therapy. Results: A typical resting tremor with a peak frequency of 4.93 ± 0.98 Hz (mean ± SD) was measured. Compared to the baseline, DBS modulated significant neuromuscular pattern changes in most features except for the peak frequency, by decreasing the motor unit firing rate, amplitude, or power and by changing the regularity pattern. Three sEMG features were detected with significant associations with the clinical improvement rate (IR) of the tremor scale: peak frequency power (R = 0.37, p = 0.03), weighted root mean square (R = 0.42, p = 0.01), and modified mean amplitude power (R = 0.48, p = 0.003). These were adopted to train a Gaussian process regression model with a leave-one-out cross-validation procedure. The prediction values from the trained sEMG prediction model (1,000 permutations, p = 0.003) showed a good correlation (r = 0.47, p = 0.0043) with the true IR of the tremor scale. Conclusion: DBS acutely modulated the intraoperative resting tremor, mainly by suppressing the amplitude and motor unit firing rate and by changing the regularity pattern, but not by modifying the frequency pattern. Three features showed strong robustness and could be used as quick intraoperative biomarkers to quantify and predict the efficacy of DBS in PD patients with resting tremor.

Pallidal versus subthalamic nucleus deep brain stimulation for levodopa-induced dyskinesia.

OBJECTIVE: To compare the efficacy of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on reducing levodopa-induced dyskinesia (LID) in Parkinson's disease, and to explore the potential underlying mechanisms. METHODS: We retrospectively assessed clinical outcomes in 43 patients with preoperative LID who underwent DBS targeting the STN (20/43) or GPi (23/43). The primary clinical outcome was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) and secondary outcomes included changes in the total daily levodopa equivalent dose, the drug-off Unified Parkinson Disease Rating Scale Part Ⅲ at the last follow-up (median, 18 months), adverse effects, and programming settings. Correlation analysis was used to find potential associated factors that could be used to predict the efficacy of DBS for dyskinesia management. RESULTS: Compared to baseline, both the STN group and the GPi group showed significant improvement in LID with 60.73 ± 40.29% (mean ± standard deviation) and 93.78 ± 14.15% improvement, respectively, according to the UDysRS score. Furthermore, GPi-DBS provided greater clinical benefit in the improvement of dyskinesia (P < 0.05) compared to the STN. Compared to the GPi group, the levodopa equivalent dose reduction was greater in the STN group at the last follow-up (43.81% vs. 13.29%, P < 0.05). For the correlation analysis, the improvement in the UDysRS outcomes were significantly associated with a reduction in levodopa equivalent dose in the STN group (r = 0.543, P = 0.013), but not in the GPi group (r = -0.056, P = 0.801). INTERPRETATION: Both STN and GPi-DBS have a beneficial effect on LID but GPi-DBS provided greater anti-dyskinetic effects. Dyskinesia suppression for STN-DBS may depend on the reduction of levodopa equivalent dose. Unlike the STN, GPi-DBS might exert a direct and independent anti-dyskinesia effect.

Integrated analysis of exosomal lncRNA and mRNA expression profiles reveals the involvement of lnc-MKRN2-42:1 in the pathogenesis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common movement disorder for which diagnosis mainly depends on the medical history and clinical symptoms. Exosomes are now considered an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids, and genetic material. Long noncoding (lnc) RNA in exosomes plays a critical role in many diseases, including neurodegenerative disease. AIM: To study expression differences for lncRNAs in peripheral blood exosomes of PD patients compared with healthy individuals and to look for lncRNAs that might be related to the pathogenesis of PD. MATERIALS AND METHODS: We recruited PD patients along with age- and sex-matched healthy individuals as healthy controls and evaluated levels of lncRNAs extracted from exosomes in plasma samples via next-generation sequencing and real-time quantitative PCR. Correlation analysis was conducted for the clinical characteristics of PD patients and the expression of selected lncRNAs. RESULTS: We found 15 upregulated and 24 downregulated exosomal lncRNAs in the PD group. According to bioinformatics analyses, we chose lnc-MKRN2-42:1 for further study. Interestingly, lnc-MKRN2-42:1 was positively correlated with the MDS-UPDRS III score for PD patients. CONCLUSION: Our study suggested that lnc-MKRN2-42:1 may be involved in the occurrence and development of PD.

Integrated transcriptome expression profiling reveals a novel lncRNA associated with L-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson's disease (PD). Long noncoding RNAs regulate gene expression and participate in many biological processes. However, the role of long noncoding RNAs in LID is not well understood. In the present study, we examined the lncRNA transcriptome profile of a rat model of PD and LID by RNA sequence and got a subset of lncRNAs, which were gradually decreased during the development of PD and LID. We further identified a previously uncharacterized long noncoding RNA, NONRATT023402.2, and its target genes glutathione S-transferase omega (Gsto)2 and prostaglandin E receptor (Ptger)3. All of them were decreased in the PD and LID rats as shown by quantitative real-time PCR, fluorescence in situ hybridization and western blotting. Pearson's correlation analysis showed that their expression was positively correlated with the dyskinesia score of LID rats. In vitro experiments by small interfering RNA confirmed that slicing NONRATT023402 inhibited Gsto2 and Ptger3 and promoted the inflammatory response. These results demonstrate that NONRATT023402.2 may have inhibitive effects on the development of PD and LID.