The severity assessment of Parkinson's disease based on plasma inflammatory factors and third ventricle width by transcranial sonography.

BACKGROUND: Predicting Parkinson's disease (PD) can provide patients with targeted therapies. However, disease severity can be roughly evaluated in clinical practice based on the patient's symptoms and signs. OBJECTIVE: The current study attempted to explore the factors linked with PD severity and construct a predictive model. METHOD: The PD patients and healthy controls were recruited from our study center while recording their basic demographic information. The serum inflammatory markers levels, such as Cystatin C (Cys C), C-reactive protein (CRP), RANTES (regulated on activation, normal T cell expressed and secreted), Interleukin-10 (IL-10), and Interleukin-6 (IL-6) were determined for all the participants. PD patients were categorized into early and mid-advanced groups based on the Hoehn and Yahr (H-Y) scale and evaluated using PD-related scales. LASSO logistic regression analysis (Model C) helped select variables based on clinical scale evaluations, serum inflammatory factor levels, and transcranial sonography measurements. The optimal harmonious model coefficient λ was determined via 10-fold cross-validation. Moreover, Model C was compared with multivariate (Model A) and stepwise (Model B) logistic regression. The area under the curve (AUC) of a receiver operator characteristic (ROC), brier score, calibration curve, and decision curve analysis (DCA) helped determine the discrimination and calibration of the predictive model, followed by configuring a forest plot and column chart. RESULTS: The study included 113 healthy individuals and 102 PD patients, with 26 early and 76 mid-advanced patients. Univariate analysis of variance screened out statistically significant differences among inflammatory markers Cys C and RANTES. The average Cys C level in the mid-advanced stage was significantly higher than in the early stage (p < 0.001) but not for RANTES (p = 0.740). The LASSO logistic regression model (λ.1se = 0.061) associated with UPDRS-I, UPDRS-II, UPDRS-III, HAMA, PDQ-39, and Cys C as the included independent variables revealed that the Model C discrimination and calibration (AUC = 0.968, Brier = 0.049) were superior to Model A (AUC = 0.926, Brier = 0.079) and Model B (AUC = 0.929, Brier = 0.071) models. CONCLUSION: The study results show multiple factors are linked with PD assessment. Moreover, the inflammatory marker Cys C and transcranial sonography measurement could objectively predict PD symptom severity, helping doctors monitor PD evolution in patients while targeting interventions.

Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.

BACKGROUND: Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies. METHODS: In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer. RESULTS: Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging. CONCLUSION: CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

The remediation potential and kinetics of Pb2+ adsorbed by the organic frameworks of Cladophora rupestris.

Cladophora rupestris is ubiquitous in many kinds of waterbodies, and C. rupestris biomass can serve as a carrier for adsorbing and transferring heavy metals. Batch experiments and characterization were performed. Results showed that the organic frameworks of C. rupestris (CROF) had a specific surface area of 2.58 m2/g and an external surface area of 2.06 m2/g. Many mesopores were present in CROF, mainly distributed in 2.5-7.5 nm. The zeta potentials were within the range of - 4.46 to - 13.98 mV in the tested pH of 2.0-9.0. CROF could effectively adsorb Pb2+ in large pH range. The maximum adsorption capacity (qmax) of Pb2+ on CROF was 15.02 mg/g, and 97% of Pb2+ was adsorbed onto CROF after 25 min. CROF had a preferential adsorption of Pb2+. The protein secondary structures and carbon skeletons of CROF all worked in adsorption. The main Pb2+ adsorption mechanisms were pore filling, electrostatic attraction, Pb-π interaction, and surface complexation. Therefore, it is valuable as a biosorbent for the removal of Pb2+ from waterbodies.

The mutual overlapping impact of stress and infection on mental health problems in adolescents and youths during and after COVID-19 pandemic in China.

BACKGROUND: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students. METHODS: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups. RESULTS: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001). LIMITATION: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms. CONCLUSION: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students.

The guiding effect of local field potential during deep brain stimulation surgery for programming in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery require subsequent programming, which is complex and cumbersome. The local field potential (LFP) in the deep brain is associated with motor symptom improvement. The current study aimed to identify LFP biomarkers correlated with improved motor symptoms in PD patients after DBS and verify their guiding role in postoperative programming. METHODS: Initially, the study included 36 PD patients undergoing DBS surgery. Temporary external electrical stimulation was performed during electrode implantation, and LFP signals around the electrode contacts were collected before and after stimulation. The stimulating contact at 6 months of programming was regarded as the optimal and effective stimulating contact. The LFP signal of this contact during surgery was analyzed to identify potential LFP biomarkers. Next, we randomly assigned another 30 PD patients who had undergone DBS to physician empirical programming and LFP biomarker-guided programming groups and compared the outcomes. RESULTS: In the first part of the study, LFP signals of electrode contacts changed after electrical stimulation. Electrical stimulation reduced gamma energy and the beta/alpha oscillation ratio. The different programming method groups were compared, indicating the superiority of beta/alpha oscillations ratio-guided programming over physician experience programming for patients' improvement rate (IR) of UPDRS-III. There were no significant differences in the IR of UPDRS-III, post-LED, IR-PDQ39, number of programmings, and the contact change rate between the gamma oscillations-guided programming and empirical programming groups. CONCLUSION: Overall, the findings reveal that gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming in PD patients after DBS. Instead of relying solely on spike action potential signals from single neurons, LFP biomarkers can provide the appropriate depth for electrode placement.

Bilateral globus pallidus interna deep brain stimulation in the treatment of mixed cerebral palsy in ataxia with dyskinesia: a case report.

Background: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined. Methods: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction. Results: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels. Conclusion: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time.

Deep brain stimulation improves central nervous system inflammation in Parkinson's disease: Evidence and perspectives.

BACKGROUND: In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD. METHODS: We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed. RESULTS: RANTES (p < 0.001) and TNF-α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (rs  = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1  = 0.644, p = 0.033 and rs2  = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF-α levels. CONCLUSION: The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.

Effect of deep brain stimulation compared with drug therapy alone on the progression of Parkinson's disease.

Background: Parkinson's disease (PD) symptoms deteriorate with disease progression. Although deep brain stimulation (DBS) can effectively improve the motor signs of PD patients, it is not yet known whether DBS surgery, which is an invasive treatment modality, may change the progression of PD. Objective: The aim of this work was to compare the effect of DBS with that of drug treatment on the progression of PD. Methods: A total of 77 patients with PD with the Hoehn and Yahr scale (HY) stage of 2.5 or 3 were included, and were divided into 34 in the drug therapy alone group (Drug-G) and 43 in the DBS therapy group (DBS-G). All patients were subjected to a follow-up of 2 years, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the Montreal Cognitive Assessment (MOCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) scores. In addition, the quality of life of patients and the burden on their family were assessed by the 39-item PD questionnaire (PDQ-39) scores, daily levodopa equivalent dose (LED), patient's annual treatment-related costs, and the Zarit Caregiver Burden Scale (ZCBS) score. The changes in relevant scale scores between the two groups were compared at each follow-up stage. Results: The UPDRS-III score of the patients in the "off" state increased from year to year in both groups, and the degree of increase of this score was greater in the DBS-G than in the Drug-G group. The MOCA score in both groups began to decline in the 2nd year of follow-up, and the decline was greater in the Drug-G than in the DBS-G group. DBS treatment did not affect patients' psychiatric disorders. The PDQ39, LED, costs, and ZCBS were negatively correlated with the follow-up time in patients in the DBS-G group, and positively correlated with the follow-up time in patients in the Drug-G. Conclusion: PD is progressive regardless of treatment. The findings from this follow-up study suggest that the disease progression of patients in DBS-G may be slightly faster compared to the drug-G, but the advantages of DBS are also evident. Indeed, DBS better improves patient's motor signs and quality of life and reduces the family burden. In addition, DBS has less impact on patients in terms of cognitive and mental effects.

A pilot study of viscoelastic agent to prevent recurrent vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy.

BACKGROUND: To evaluate the possibilty of preventing recurrent vitreous hemorrhage (RVH) after vitrectomy in proliferative diabetic retinopathy (PDR) patients with unabsorbed vitreous hemorrhage (VH) by intravitreal injection of viscoelastic agent (VA) at the end of the surgery and compared its effect with triamcinolone acetonide (TA). METHODS: This was a pilot prospective, observational study. PDR patients with VH who underwent vitrectomy were assigned to 3 groups according to the tamponade applicated at the end of the surgery, including VA group (intravitreally injected 1 ml VA if the retina was prone to bleed during the operation), TA group (intravitreally injected 2 mg TA when there was much exudates), or balanced salt solution (BSS) group (no tamponade). Then postoperative follow-up was performed routinely until 6 months after surgery. The primary outcome was the incidence of RVH, secondary outcome were the best-corrected visual acuity (BCVA) and introcular pressure (IOP). Cataract formation and other complication were also assessed. RESULTS: A total of 68 eyes, from 68 patients, were included. 18,18,32 eyes were enrolled in the VA group, TA group and BSS group, respectively. The integral incidence of RVH after vitrectomy was 5.6%, 5.6% and 12.5% respectively (P = 0.602). There was no early RVH in VA or TA group, whereas 3 early RVHs were identified in BSS group, however there was no significant difference (P = 0.171). Every group had one late RVH case. In all groups, final BCVA showed significant improvement compared to baseline. BCVA at any postoperative visit showed no significant differences among 3 groups. Mean IOP was higher 1 week after surgery in VA group compared with the other groups; however, in other times the differences were not significant. No cataract formation and other complication was noted in 3 groups. CONCLUSION: Intravitreal injection of VA or TA at the end of vitrectomy for PDR patients with unabsorbed VH tend to reduce the incidence of early RVH after vitrectomy similarly. As VA was preferred to applicate in the eyes that were prone to bleed, intravitreal injection of VA at the end of vitrectomy might be a promising method for preventing RVH in PDR patients.

Altered brain network centrality in Parkinson's disease patients after deep brain stimulation: a functional MRI study using a voxel-wise degree centrality approach.

OBJECTIVE: After deep brain stimulation (DBS), patients with Parkinson's disease (PD) show improved motor symptoms and decreased verbal fluency, an effect that occurs before the initiation of DBS in the subthalamic nucleus. However, the underlying mechanism remains unclear. This study aimed to evaluate the effects of DBS on whole-brain degree centrality (DC) and seed-based functional connectivity (FC) in PD patients. METHODS: The authors obtained resting-state functional MRI data of 28 PD patients before and after DBS surgery. All patients underwent MRI scans in the off-stimulation state. The DC method was used to evaluate the effects of DBS on whole-brain FC at the voxel level. Seed-based FC analysis was used to examine network function changes after DBS. RESULTS: After DBS surgery, PD patients showed significantly weaker DC values in the left middle temporal gyrus, left supramarginal gyrus, and left middle frontal gyrus, but significantly stronger DC values in the midbrain, left precuneus, and right precentral gyrus. FC analysis revealed decreased FC values within the default mode network (DMN). CONCLUSIONS: This study demonstrated that the DC of DMN-related brain regions decreased in PD patients after DBS surgery, whereas the DC of the motor cortex increased. These findings provide new evidence for the neural effects of DBS on voxel-based whole-brain networks in PD patients.

Reciprocal perspective as a super learner improves drug-target interaction prediction (MUSDTI).

The identification of novel drug-target interactions (DTI) is critical to drug discovery and drug repurposing to address contemporary medical and public health challenges presented by emergent diseases. Historically, computational methods have framed DTI prediction as a binary classification problem (indicating whether or not a drug physically interacts with a given protein target); however, framing the problem instead as a regression-based prediction of the physiochemical binding affinity is more meaningful. With growing databases of experimentally derived drug-target interactions (e.g. Davis, Binding-DB, and Kiba), deep learning-based DTI predictors can be effectively leveraged to achieve state-of-the-art (SOTA) performance. In this work, we formulated a DTI competition as part of the coursework for a senior undergraduate machine learning course and challenged students to generate component DTI models that might surpass SOTA models and effectively combine these component models as part of a meta-model using the Reciprocal Perspective (RP) multi-view learning framework. Following 6 weeks of concerted effort, 28 student-produced component deep-learning DTI models were leveraged in this work to produce a new SOTA RP-DTI model, denoted the Meta Undergraduate Student DTI (MUSDTI) model. Through a series of experiments we demonstrate that (1) RP can considerably improve SOTA DTI prediction, (2) our new double-cold experimental design is more appropriate for emergent DTI challenges, (3) that our novel MUSDTI meta-model outperforms SOTA models, (4) that RP can improve upon individual models as an ensembling method, and finally, (5) RP can be utilized for low computation transfer learning. This work introduces a number of important revelations for the field of DTI prediction and sequence-based, pairwise prediction in general.

Tuning the Surface Characteristics and Mechanical Properties of Y2O3 Coatings on a Graphene Matrix via Laser Micro Melting.

The effects of laser parameters on the microstructure and properties of plasma-sprayed yttrium oxide coating on the graphite matrix were investigated. Tensile strength, porosity, roughness, and scratch meter tests were carried out to evaluate the critical load and mechanical properties of the coating after spraying and laser micro-melting. When the porosity and surface roughness of the coating are minimum, the critical load of the coating is 7.85 N higher than that of the spraying surface. After laser micromelting, the crystal phase of Y2O3 coating surface does not change, the crystallinity is improved, and fine grain strengthening occurs. When the laser power density is 75 W/mm2, the scanning speed is 30 mm/s, and the defocusing distance is 40 mm, the film base bonding performance and wear resistance of the material reach the maximum value. The failure of Y2O3 coating is mainly due to the degradation of mechanical properties such as film base bonding strength, surface porosity, and surface roughness, which leads to the local collapse of the material. The coating after laser micro-melting only presents particle disintegration at the end of the scratch area.

Development of Unilateral Peri-Lead Edema Into Large Cystic Cavitation After Deep Brain Stimulation: A Case Report.

Background and Importance: Deep brain stimulation (DBS) has been approved to treat a variety of movement disorders, including Parkinson's disease (PD), essential tremor, and dystonia. Following the DBS surgery, some perioperative and even delayed complications due to intracranial and hardware-related events could occur, which may be life-threatening and require immediate remedial measures. Clinical Presentation: We report a case of an older woman with advanced PD who developed the unique complication of unilateral cyst formation at the tip of the DBS electrode after undergoing bilateral placement of subthalamic nucleus DBS. After a period of controlled motor symptoms, the patient showed new neurological deficits related to right peri-lead edema. However, the new neurological symptoms regressed quickly over several days with stereotactic implantation of a puncture needle to drain the cyst fluid without removing the affected lead. Conclusion: The occurrence of an intraparenchymal cyst following DBS surgery is a rare but life-threatening complication that could relate to edema around the electrodes or cerebrospinal fluid tracking. Stereotactic aspiration makes the intracranial cyst regress safely and effectively and ensures that the electrode is in the optimal position of the target nucleus to achieve an effective DBS surgery.

The Effects of Different Anesthesia Methods on the Treatment of Parkinson's Disease by Bilateral Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) surgery for Parkinson's disease (PD) is routinely performed at medical centers worldwide. However, it is debated whether general anesthesia (GA) or traditional local anesthetic (LA) is superior. Purpose: This study aims to compare the effects of LA and GA operation methods on clinical improvement in patients with PD, such as motor and non-motor symptoms, after STN-DBS surgery at our center. Method: A total of 157 patients with PD were retrospectively identified as having undergone surgery under LA (n = 81) or GA (n = 76) states. In this study, the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III) in three states, levodopa-equivalent-daily-dose (LEDD), surgical duration, intraoperative microelectrode recording (iMER) signal length, postoperative intracranial volume, electrode implantation error, neuropsychological function, quality of life scores, and complication rates were collected and compared. All patients with PD were routinely followed up at 6, 12, 18, and 24 months postoperatively. Result: Overall improvement in UPDRS-III was demonstrated at postoperative follow-up, and there was no significant difference between the two groups in medication-off, stimulation-off state and medication-off, stimulation-on state. However, UPDRS-III scores in medication-on, stimulation-on state under GA was significantly lower than that in the LA group. During postoperative follow-up, LEDD in the LA group (6, 12, 18, and 24 months, postoperatively) was significantly lower than in the GA group. However, there were no significant differences at baseline or 1-month between the two groups. The GA group had a shorter surgical duration, lower intracranial volume, and longer iMER signal length than the LA group. However, there was no significant group difference in electrode implantation accuracy and complication rates. Additionally, the Hamilton Anxiety Scale (HAMA) was significantly lower in the GA group than the LA group at 1-month follow-up, but this difference disappeared at longer follow-up. Besides, there was no significant group difference in the 39-item Parkinson's Disease Questionnaire (PDQ-39) scale scores. Conclusion: Although both groups showed overall motor function improvement without a significant postoperative difference, the GA group seemed superior in surgical duration, intracranial volume, and iMER signal length. As the accuracy of electrode implantation can be ensured by iMER monitoring, DBS with GA will become more widely accepted.

Altered Interhemispheric Functional Connectivity Associated With Early Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease.

Background: Patients with Parkinson's disease (PD) experience a decline in verbal fluency (VF) immediately after undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN). This phenomenon is thought to be related to surgical microlesions. Purpose: We investigated the alterations in interhemispheric functional connectivity after STN-DBS in PD patients. We also evaluated the correlation between these changes and decreased VF scores. Method: Overall, 30 patients with PD were enrolled in the study. Resting-state functional magnetic resonance imaging scans were performed twice, once before and once after DBS, in PD patients. Voxel-mirrored homotopic connectivity (VMHC) was applied in order to evaluate the synchronicity of functional connectivity between the hemispheres. Result: After undergoing STN-DBS, PD patients demonstrated reduced VMHC value in the posterior cerebellum lobe, angular gyrus, precuneus/posterior cingulate gyrus (PCC), supramarginal gyrus, superior frontal gyrus (SFG) (medial and dorsolateral) and middle frontal gyrus (MFG). In addition, we observed a significant positive correlation between the altered VMHC value in the SFG and MFG and the change of phonemic VF scores. Conclusion: PD patients demonstrated an interhemispheric coordination disorder in the prefrontal cortex, cerebellum, supramarginal gyrus and DMN after undergoing STN-DBS. The positive correlation between reduced VMHC value in the SFG and MFG and the changes of VF scores provides a novel understanding with regard to the decline of VF after DBS.

China's Economic Forecast Based on Machine Learning and Quantitative Easing.

In this paper, six variables, including export value, real exchange rate, Chinese GDP, and US IPI, and their seasonal variables, are used as determinants to model and forecast China's export value to the US using three methods: BP neural network, ARIMA, and AR-GARCH. Error indicators were chosen to compare the simulated and predicted results of the three models with the real values. It is found that the results of all three models are satisfactory, although there are some differences in their simulation and forecasting capabilities, but the ARIMA model has a clear advantage. This paper analyses the reasons for these results and proposes suggestions for improving China's exports in the context of the models.

Epigenetic modifications in chronic rhinosinusitis with and without nasal polyps.

Chronic rhinosinusitis (CRS) has brought a huge socioeconomic burden. However, its mechanism is still elusive, which may involve genetic, environmental and some other factors. Epigenetic analyses have been conducted to explore the mechanisms underlying CRS. Here, we reviewed the fruits in the epigenetic studies on DNA methylation, histone modification, and non-coding RNA regulation. We concluded that the epigenetic research on CRS has made great breakthroughs, especially in the past 5 years and the field of microRNAs. "Epigenetic therapies" are expected to be designed to treat CRS in the future.

Inhibition of glioblastoma progression by Urolithin A in vitro and in vivo by regulating Sirt1-FOXO1 axis via ERK/AKT signaling pathways.

Glioblastoma (GBM) is the most universal and devastating primary intracranial neoplasm in the central nervous system. Urolithin A (UA) possesses many pharmacological and biological activities, but its function in GBM is not clear. CCK-8 and colony formation test were used to measure the anti-proliferative potency of UA against GBM cells. Flow cytometry was applied to evaluate cell cycle arrest and apoptosis of U251 and U118 MG cells upon UA incubation. Quantitative real-time PCR and western blotting were conducted to test the regulatory effect of UA on the expression of Sirt1 and FOXO1. Immunodeficient mice were implanted with GBM cells for in vivo validation of the anti-cancer effect of UA. We found UA repressed the proliferation, migration and invasion of glioblastoma cells, while also inhibiting the induction of colony formation ability and epithelial to mesenchymal transition (EMT) in a time- or dose-dependent manner. The does-dependent relationship of UA inducing the cell cycle arrest and apoptosis of glioblastoma cells was identified. Furthermore, UA could enhance the expression levels of Sirt1 and FOXO1 and the knockdown of Sirt1 blocked the inhibitory effects of UA on the proliferation and migration of glioblastoma cells and correspondingly modified the expression level of FOXO1. Overexpression of Sirt1 restored the despaired inhibitory effect of UA induced by Sirt1 knockout on the proliferation and migration of glioblastoma cells. In animal experiments, UA decreased the tumor size and weight of glioblastoma in xenograft nude mice and promoted the expression of Sirt1 and FOXO1 in transplanted tumors. Our findings presented in this study indicate that UA exerts a repressive effect on glioblastoma cells in vivo and in vitro by regulating the Sirt1-FOXO1 axis via the ERK and AKT pathways, indicating that UA is a new novel therapeutic candidate for the treatment of glioblastoma.

Altered Regional Homogeneity and Functional Connectivity during Microlesion Period after Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) undergoing deep brain electrode implantation experience a temporary improvement in motor symptoms before the electrical stimulation begins. We usually call this the microlesion effect (MLE), but the mechanism behind it is not clear. PURPOSE: This study aimed to assess the alterations in brain functions at the regional and whole-brain levels, using regional homogeneity (ReHo) and functional connectivity (FC), during the postoperative microlesion period after deep brain stimulation (DBS) in PD patients. METHOD: Resting-state functional MRI data were collected from 27 PD patients before and after the first day of DBS and 12 healthy controls (HCs) in this study. The ReHo in combination with FC analysis was used to investigate the alterations of regional brain activity in all the subjects. RESULTS: There were increased ReHo in the basal ganglia-thalamocortical circuit (left supplementary motor area and bilateral paracentral lobule), whereas decreased ReHo in the default mode network (DMN) (left angular gyrus, bilateral precuneus), prefrontal cortex (bilateral middle frontal gyrus), and the cerebello-thalamocortical (CTC) circuit (Cerebellum_crus2/1_L) after DBS. In addition, we also found abnormal FC in the lingual gyrus, cerebellum, and DMN. CONCLUSION: Microlesion of the thalamus caused by electrode implantation can alter the activity of the basal ganglia-thalamocortical circuit, prefrontal cortex, DMN, and CTC circuit and induce abnormal FC in the lingual gyrus, cerebellum, prefrontal cortex, and DMN among PD patients. The findings of this study contribute to the understanding of the mechanism of MLE.

Altered Spontaneous Neural Activity and Functional Connectivity in Parkinson's Disease With Subthalamic Microlesion.

BACKGROUND: Transient improvement in motor symptoms are immediately observed in patients with Parkinson's disease (PD) after an electrode has been implanted into the subthalamic nucleus (STN) for deep brain stimulation (DBS). This phenomenon is known as the microlesion effect (MLE). However, the underlying mechanisms of MLE is poorly understood. PURPOSE: We utilized resting state functional MRI (rs-fMRI) to evaluate changes in spontaneous brain activity and networks in PD patients during the microlesion period after DBS. METHOD: Overall, 37 PD patients and 13 gender- and age-matched healthy controls (HCs) were recruited for this study. Rs-MRI information was collected from PD patients three days before DBS and one day after DBS, whereas the HCs group was scanned once. We utilized the amplitude of low-frequency fluctuation (ALFF) method in order to analyze differences in spontaneous whole-brain activity among all subjects. Furthermore, functional connectivity (FC) was applied to investigate connections between other brain regions and brain areas with significantly different ALFF before and after surgery in PD patients. RESULT: Relative to the PD-Pre-DBS group, the PD-Post-DBS group had higher ALFF in the right putamen, right inferior frontal gyrus, right precentral gyrus and lower ALFF in right angular gyrus, right precuneus, right posterior cingulate gyrus (PCC), left insula, left middle temporal gyrus (MTG), bilateral middle frontal gyrus and bilateral superior frontal gyrus (dorsolateral). Functional connectivity analysis revealed that these brain regions with significantly different ALFF scores demonstrated abnormal FC, largely in the temporal, prefrontal cortices and default mode network (DMN). CONCLUSION: The subthalamic microlesion caused by DBS in PD was found to not only improve the activity of the basal ganglia-thalamocortical circuit, but also reduce the activity of the DMN and executive control network (ECN) related brain regions. Results from this study provide new insights into the mechanism of MLE.