Zanubrutinib delays selinexor resistance evolution in biopsy sample-derived primary central nervous system lymphoma models.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive lymphoma of the brain with poor prognosis. The scarcity of cell lines established using PCNSL makes it difficult to conduct preclinical studies on new drugs. We aimed to explore the effect of selinexor combined with zanubrutinib in PCNSL using established PCNSL cells and an orthotopic PCNSL model. Primary PCNSL cells were successfully cultured. Selinexor inhibited proliferation, induced G1 phase arrest, and promoted apoptosis, however, induced drug resistance in PCNSL. Selinexor combined with zanubrutinib had a synergistic effect on PCNSL and prevented the onset of selinexor resistance in PCNSL by inhibiting AKT signaling. Moreover, selinexor combined with zanubrutinib notably slowed tumor growth and prolonged survival compared to that of the control. Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in vitro and prolonged survival in vivo.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

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.

Transcriptome sequencing of circular RNA reveals the involvement of hsa-SCMH1_0001 in the pathogenesis of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease. Exosomes are endosome-derived extracellular vesicles that can take part in intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs characterized by covalently closed-loop structures, which perform a crucial function in many diseases. AIM: To clarify the expression and function of exosomal circRNSs of PD patients and look for circRNAs that might be related to the pathogenesis of PD. MATERIALS AND METHODS: We examined circRNA and mRNA expression profiles in peripheral exosomes from PD patients (n = 23) and healthy controls (n = 15) using next-generation sequencing (NGS) technology, functional annotation, and quantitative polymerase chain reaction. Correlation analysis was performed between the expression levels of the circRNAs and the clinical characteristics of PD patients. The binding miRNAs and target genes were predicted using TargetScanHuman, miRDB, and miRTarBase. The predicted target genes were compared with the differentially expressed mRNAs in sequencing results. RESULTS: According to the NGS, 62 upregulated and 37 downregulated circRNAs in the PD group were screened out. Correlation analysis revealed that hsa-SCMH1_0001 has strong clinical relevance. We identified 17 potential binding miRNAs of hsa-SCMH1_0001 with 149 potential target genes. ARID1A and C1orf115 belong to the intersection of the predicted target genes and the differentially expressed mRNAs obtained by sequencing. CONCLUSION: This study suggested that hsa-SCMH1_0001 and its target genes ARID1A and C1orf115 are downregulated in PD patients and may be involved in the occurrence of PD.

Masson pine pollen aqueous extract ameliorates cadmium-induced kidney damage in rats.

Introduction: Cadmium (Cd) is a hazardous environmental pollutant present in soil, water, and food. Accumulation of Cd in organisms can cause systematic injury and damage to the kidney. The Masson pine pollen aqueous extract (MPPAE) has attracted increasing attention due to its antioxidant activity and ability to enhance immunity. Methods: In this study, we investigated the potential of MPPAE to protect against Cd-induced kidney damage in rats and the underlying mechanism. The transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, were explored. Results: The concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were both significantly altered after treatment with MPPAE. Furthermore, sequencing and analysis of the transcriptome and metabolome of rats with Cd-induced kidney damage, following treatment with MPPAE, revealed differential expression of numerous genes and metabolites compared with the untreated control rats. These differentially expressed genes (DEGs) included detoxification-related genes such as cytochrome P450 and the transporter. The differentially expressed metabolites (DEMs) included 4-hydroxybenzoic acid, L-ascorbate, and ciliatine. Conjoint transcriptome and metabolome analysis showed that several DEGs were correlated with DEMs. Conclusion: These preliminary findings indicate the potential of MPPAE for the treatment of toxic metal poisoning.

Neurosurgical robots in China: State of the art and future prospect.

Neurosurgical robots have developed for decades and can effectively assist surgeons to carry out a variety of surgical operations, such as biopsy, stereo-electroencephalography (SEEG), deep brain stimulation (DBS), and so forth. In recent years, neurosurgical robots in China have developed rapidly. This article will focus on several key skills in neurosurgical robots, such as medical imaging systems, automatic manipulator, lesion localization techniques, multimodal image fusion technology, registration method, and vascular imaging technology; introduce the clinical application of neurosurgical robots in China, and look forward to the potential improvement points in the future based on our experience and research in the field.

The NONRATT023402.2/rno-miR-3065-5p/NGFR axis affects levodopa-induced dyskinesia in a rat model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) is a common motor complication in Parkinson's disease. However, few studies have focused on the pathogenesis of LID at the transcriptional level. NONRATT023402.2, a long non-coding RNA (lncRNA) that may be related to LID was discovered in our previous study and characterized in rat models of LID. In the present study, NONRATT023402.2 was overexpressed by injection of adeno-associated virus (AAV) in striatum of LID rats, and 48 potential target genes, including nerve growth factor receptor (NGFR) were screened using next-generation sequencing and target gene predictions. The NONRATT023402.2/rno-miR-3065-5p/NGFR axis was verified using a dual luciferase reporter gene. Overexpression of NONRATT023402.2 significantly increased the abnormal involuntary movements (AIM) score of LID rats, activated the PI3K/Akt signaling pathway, and up-regulated c-Fos in the striatum. NGFR knockdown by injection of ShNGFR-AAV into the striatum of LID rats resulted in a significant decrease in the PI3K/Akt signaling pathway and c-Fos expression. The AIM score of LID rats was positively correlated with the expressions of NONRATT023402.2 and NGFR. A dual luciferase reporter assay showed that c-Fos, as a transcription factor, bound to the NONRATT023402.2 promoter and activated its expression. Together, the results showed that NONRATT023402.2 regulated NGFR expression via a competing endogenous RNA mechanism, which then activated the PI3K/Akt pathway and promoted c-Fos expression. This suggested that c-Fos acted as a transcription factor to activate NONRATT023402.2 expression, and form a positive feedback regulation loop in LID rats, thus, aggravating LID symptoms. NONRATT023402.2 is therefore a possible novel therapeutic target for LID.

Utilization, surgical populations, centers, coverages, regional balance, and their influential factors of deep brain stimulation for Parkinson's disease: a large-scale multicenter cross-sectional study from 1997 to 2021.

BACKGROUND: Deep brain stimulation (DBS) is an emerging and effective therapy for Parkinson's disease (PD). However, little is known about its utilization, surgical populations, centers, coverages, regional balance, and influential factors. MATERIALS AND METHODS: This large-scale multicenter cross-sectional study was conducted using a national census involving 74 Chinese centers. National DBS populations and centers for PD were investigated in 1997-2021, and regional sociodemographic features, surgical populations, related resources, and insurance policies in 2020 were explored. RESULTS: Since the first DBS surgery in 1997, a total of 38 122 PD patients from 349 centers underwent DBS by 2021, which covered 1.118% (1.108-1.129) of patients and 0.954% (0.933-0.976) of centers. Significant upward trends in the annual surgical population and coverages were observed with rapid climbing rates, while the annual surgical centers and their coverage showed two growth peaks in 2002-2006 and 2010-2018, correlating with clinical approvals and new technologies. A total of 103 070 (51 165-154 975) PD patients [2.088% (1.351-2.825) coverage] and 603 (72-1134) centers [1.356% (1.126-1.586) coverage] are predicted to conduct DBS by 2030. The new remotely programmed DBS technology was recoded as the first application in 2015 and rapidly increased to 2771 (47.39%, 46.11-48.67) patients with 10 507 remote programming sessions annually in 2021. Provinces in the eastern and central regions had better economic status, more surgical patients, higher insurance affordability, and more related resources than those in the western and northeastern regions. Higher gross domestic product per capita ( ß =5.041, 3.324-6.758 and ß =0.008, 0.004-0.012; all P <0.001) and more functional neurosurgery doctors ( ß =3.596, 0.353-6.839; P =0.031 and ß =0.010, 0.002-0.017; P =0.013) positively influenced surgical populations and coverages, while higher insurance levels ( ß =128.888, 64.702-193.075; P <0.001) positively influenced surgical coverages. CONCLUSION: Although surgical populations, centers, and coverages of DBS for PD have rapidly improved and are predicted to show future increases, this is still insufficient to cover potential eligible patients. Regionally imbalanced health coverage should be given attention to promote coordinated development.

Identification of influential observations in high-dimensional survival data through robust penalized Cox regression based on trimming.

Penalized Cox regression can efficiently be used for the determination of biomarkers in high-dimensional genomic data related to disease prognosis. However, results of Penalized Cox regression is influenced by the heterogeneity of the samples who have different dependent structure between survival time and covariates from most individuals. These observations are called influential observations or outliers. A robust penalized Cox model (Reweighted Elastic Net-type maximum trimmed partial likelihood estimator, Rwt MTPL-EN) is proposed to improve the prediction accuracy and identify influential observations. A new algorithm AR-Cstep to solve Rwt MTPL-EN model is also proposed. This method has been validated by simulation study and application to glioma microarray expression data. When there were no outliers, the results of Rwt MTPL-EN were close to the Elastic Net (EN). When outliers existed, the results of EN were impacted by outliers. And whenever the censored rate was large or low, the robust Rwt MTPL-EN performed better than EN. and could resist the outliers in both predictors and response. In terms of outliers detection accuracy, Rwt MTPL-EN was much higher than EN. The outliers who "lived too long" made EN perform worse, but were accurately detected by Rwt MTPL-EN. Through the analysis of glioma gene expression data, most of the outliers identified by EN were those "failed too early", but most of them were not obvious outliers according to risk estimated from omics data or clinical variables. Most of the outliers identified by Rwt MTPL-EN were those who "lived too long", and most of them were obvious outliers according to risk estimated from omics data or clinical variables. Rwt MTPL-EN can be adopted to detect influential observations in high-dimensional survival data.

A retrospective evaluation of Bayesian-penalized likelihood reconstruction for [15O]H2O myocardial perfusion imaging.

BACKGROUND: New Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: We analyzed cardiac [15O]H2O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml-1⋅min-1 vs 1.86 ± 0.21 g⋅ml-1⋅min-1) and no ischemia (3.26 ± 0.34 g⋅ml-1⋅min-1 vs 3.28 ± 0.34 g⋅ml-1⋅min-1). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml-1⋅min-1 and 1.12 ± 0.06 g⋅ml-1⋅min-1). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions CONCLUSION: OSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [15O]H2O PET due to suspected obstructive coronary artery disease.

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.

[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.

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.

Myocardial perfusion quantification with Rb-82 PET: good interobserver agreement of Carimas software on global, regional, and segmental levels.

PURPOSE: To estimate the interobserver agreement of the Carimas software package (SP) on global, regional, and segmental levels for the most widely used myocardial perfusion PET tracer-Rb-82. MATERIALS AND METHODS: Rest and stress Rb-82 PET scans of 48 patients with suspected or known coronary artery disease (CAD) were analyzed in four centers using the Carimas SP. We considered values to agree if they simultaneously had an intraclass correlation coefficient (ICC) > 0.75 and a difference < 20% of the median across all observers. RESULTS: The median values on the segmental level were 1.08 mL/min/g for rest myocardial blood flow (MBF), 2.24 mL/min/g for stress MBF, and 2.17 for myocardial flow reserve (MFR). For the rest MBF and MFR, all the values at all the levels fulfilled were in excellent agreement. For stress MBF, at the global and regional levels, all the 24 comparisons showed excellent agreement. Only 1 out of 102 segmental comparisons (seg. 14) was over the adequate agreement limit-23.5% of the median value (ICC = 0.95). CONCLUSION: Interobserver agreement for Rb-82 PET myocardial perfusion quantification analyzed with Carimas is good at any LV segmentation level-global, regional, and segmental. It is good for all the estimates-rest MBF, stress MBF, and MFR.

Relationship between electrode position of deep brain stimulation and motor symptoms of Parkinson's disease.

BACKGROUND: To investigate the relationship between the position of bilateral STN-DBS location of active contacts and the clinical efficacy of STN-DBS on motor symptoms in Parkinson's disease (PD) patients. METHODS: Retrospectively analyze the clinical data of 57 patients with PD who underwent bilateral STN-DBS from March 2018 to December 2018. Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39) before operation and within 6 months after operation, determine the location of activated contacts and volume of tissue activated (VTA) in the Montreal Neurological Institute (MNI) space, and analyze their correlation with the improvement rate of motor symptoms (UPDRS-III score improvement rate). RESULTS: After 6 months of follow up, the UPDRS-III scores of 57 patients (Med-off) were improved by 55.4 ± 18.9% (P<0.001) compared with that before operation. The improvement rate of PDQ-39 scores [(47.4 ± 23.2)%, (P < 0.001)] and the reduction rate of LEDD [(40.1 ± 24.3)%, (P < 0.01)] at 6 months postoperation were positively correlated with the improvement rate of motor symptoms (Med-off)(PDQ-39:r = 0.461, P<0.001; LEDD: r = 0.354, P = 0.007), the improvement rate of UPDRS-III (Med-off) and the Z-axis coordinate of the active contact in the MNI space were positively correlated (left side: r = 0.349,P = 0.008;right side: r = 0.369,P = 0.005). In the MNI space, there was no correlation between the UPDRS-III scores improvement rate (Med-off) at 6 months after operation and bilateral VTA in the STN motor subregion, STN associative subregion and STN limbic subregion of the active electrode contacts of 57 patients (all P > 0.05). At 6 months after surgery, the difference between the Z-axis coordinate in the different improvement rate subgroups(<25, 25 to 50%, and>50%) in the MNI space was statistically significant (left side: P = 0.030; right side: P = 0.024). In the MNI space, there was no statistically significant difference between the groups in the VTA of the electrode active contacts (all P > 0.05). CONCLUSION: STN-DBS can improve the motor symptoms of PD patients and improve the quality of life. The closer the stimulation is to the STN dorsolateral sensorimotor area, the higher the DBS is to improve the motor symptoms of PD patients.

Quantification of Myocardial Dosimetry and Glucose Metabolism Using a 17-Segment Model of the Left Ventricle in Esophageal Cancer Patients Receiving Radiotherapy.

OBJECTIVE: Previous studies have shown that increased cardiac uptake of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET) may be an indicator of myocardial injury after radiotherapy (RT). The primary objective of this study was to quantify cardiac subvolume dosimetry and 18F-FDG uptake on oncologic PET using a 17-segment model of the left ventricle (LV) and to identify dose limits related to changes in cardiac 18F-FDG uptake after RT. METHODS: Twenty-four esophageal cancer (EC) patients who underwent consecutive oncologic 18F-FDG PET/CT scans at baseline and post-RT were enrolled in this study. The radiation dose and the 18F-FDG uptake were quantitatively analyzed based on a 17-segment model. The 18F-FDG uptake and doses to the basal, middle and apical regions, and the changes in the 18F-FDG uptake for different dose ranges were analyzed. RESULTS: A heterogeneous dose distribution was observed, and the basal region received a higher median mean dose (18.36 Gy) than the middle and apical regions (5.30 and 2.21 Gy, respectively). Segments 1, 2, 3, and 4 received the highest doses, all of which were greater than 10 Gy. Three patterns were observed for the myocardial 18F-FDG uptake in relation to the radiation dose before and after RT: an increase (5 patients), a decrease (13 patients), and no change (6 patients). In a pairing analysis, the 18F-FDG uptake after RT decreased by 28.93 and 12.12% in the low-dose segments (0-10 Gy and 10-20 Gy, respectively) and increased by 7.24% in the high-dose segments (20-30 Gy). CONCLUSION: The RT dose varies substantially within LV segments in patients receiving thoracic EC RT. Increased 18F-FDG uptake in the myocardium after RT was observed for doses above 20 Gy.

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.

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.