An improved gray wolf optimization algorithm solving to functional optimization and engineering design problems.

As a newly proposed optimization algorithm based on the social hierarchy and hunting behavior of gray wolves, grey wolf algorithm (GWO) has gradually become a popular method for solving the optimization problems in various engineering fields. In order to further improve the convergence speed, solution accuracy, and local minima escaping ability of the traditional GWO algorithm, this work proposes a multi-strategy fusion improved gray wolf optimization (IGWO) algorithm. First, the initial population is optimized using the lens imaging reverse learning algorithm for laying the foundation for global search. Second, a nonlinear control parameter convergence strategy based on cosine variation is proposed to coordinate the global exploration and local exploitation ability of the algorithm. Finally, inspired by the tunicate swarm algorithm (TSA) and the particle swarm algorithm (PSO), a nonlinear tuning strategy for the parameters, and a correction based on the individual historical optimal positions and the global optimal positions are added in the position update equations to speed up the convergence of the algorithm. The proposed algorithm is assessed using 23 benchmark test problems, 15 CEC2014 test problems, and 2 well-known constraint engineering problems. The results show that the proposed IGWO has a balanced E&P capability in coping with global optimization as analyzed by the Wilcoxon rank sum and Friedman tests, and has a clear advantage over other state-of-the-art algorithms.

The association of CSF biomarkers and cognitive decline with choroid plexus volume in early Parkinson's disease.

OBJECTIVE: This study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume. METHODS: Data on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects. RESULTS: At baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aß1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aß1-42/αsyn ratio. CONCLUSION: CP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins.

Neuronavigated repetitive transcranial magnetic stimulation improves depression, anxiety and motor symptoms in Parkinson's disease.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a potential treatment option for Parkinson's disease patients with depression (DPD), but conflicting results in previous studies have questioned its efficacy. Method: To investigate the safety and efficacy of neuronavigated high-frequency rTMS at the left DLPFC in DPD patients, we conducted a randomized, double-blind, sham-controlled study (NCT04707378). Sixty patients were randomly assigned to either a sham or active stimulation group and received rTMS for ten consecutive days. The primary outcome was HAMD, while secondary outcomes included HAMA, MMSE, MoCA and MDS-UPDRS-III. Assessments were performed at baseline, immediately after treatment, 2 weeks, and 4 weeks post-treatment. Results: The GEE analysis showed that the active stimulation group had significant improvements in depression, anxiety, and motor symptoms at various time points. Specifically, there were significant time-by-group interaction effects in depression immediately after treatment (ß, -4.34 [95% CI, -6.90 to -1.74; P = 0.001]), at 2 weeks post-treatment (ß, -3.66 [95% CI, -6.43 to -0.90; P = 0.010]), and at 4 weeks post-treatment (ß, -4.94 [95% CI, -7.60 to -2.29; P < 0.001]). Similarly, there were significant time-by-group interaction effects in anxiety at 4 weeks post-treatment (ß, -2.65 [95% CI, -4.96 to -0.34; P = 0.024]) and in motor symptoms immediately after treatment (ß, -5.72 [95% CI, -9.10 to -2.34; P = 0.001] and at 4 weeks post-treatment (ß, -5.43 [95% CI, -10.24 to -0.61; P = 0.027]). Conclusion: The study suggested that neuronavigated high-frequency rTMS at left DLPFC is effective for depression, anxiety, and motor symptoms in PD patients.

Motor progression phenotypes in early-stage Parkinson's Disease: A clinical prediction model and the role of glymphatic system imaging biomarkers.

BACKGROUND: Substantial heterogeneity of motor symptoms in Parkinson's disease (PD) poses a challenge to disease prediction. OBJECTIVES: The aim of this study was to construct a nomogram model that can distinguish different longitudinal trajectories of motor symptom changes in early-stage PD patients. METHODS: Data on 90 patients with 5-years of follow-up were collected from the Parkinson's Progression Marker Initiative (PPMI) cohort. We used a latent class mixed modeling (LCMM) to identify distinct progression patterns of motor symptoms, and backward stepwise logistic regression with baseline information was conducted to identify the potential predictors for motor trajectory and to develop a nomogram. The performance of the nomogram model was then evaluated using the optimism-corrected C-index for internal validation, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for discrimination, the calibration curve for predictive accuracy, and decision curve analysis (DCA) for its clinical value. RESULTS: We identified two trajectories for motor progression patterns. The first, Class 1 (Motor deteriorated group), was characterized by sustained, continuously worsening motor symptoms, and the second, Class 2 (Motor stable group), had stable motor symptoms throughout the follow-up period. The best combination of 7 baseline variables was identified and assembled into the nomogram: Scopa-AUT [odds ratio (OR), 1.11; p = 0.091], Letter number sequencing (LNS) (OR, 0.76; p = 0.068), the asymmetry index of putamen (OR, 0.95; p = 0.034), mean caudate uptake (OR, 0.14; p = 0.086), CSF pTau/α-synuclein (OR, 0.00; p = 0.011), CSF tTau/Aß (OR, 25434806; p = 0.025), and the index for diffusion tensor image analysis along the perivascular space (ALPS-index) (OR, 0.02; p = 0.030). The nomogram achieved good discrimination, with an original AUC of 0.901 (95% CI, 0.813-0.989), and the bias-corrected concordance index (C-index) with 1,000 bootstraps was 0.834. The calibration curve and DCA also suggested both the high accuracy and clinical usefulness of the nomogram, respectively. CONCLUSIONS: This study proposes an effective nomogram to predict different motor progression patterns in early-stage PD. Furthermore, the imaging biomarker indicating glymphatic function could be an independent predictive factor for PD motor progression.

The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross-Sectional Studies.

OBJECTIVE: Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, the clinical evidence of this association remains lacking. METHODS: In this study, the index for diffusion tensor image analysis along the perivascular space (ALPS index) was calculated to evaluate glymphatic function. RESULTS: Overall, 289 patients with PD were enrolled in the cross-sectional study. The ALPS index was found to be negatively correlated with age, disease severity, and dyskinesia. In the longitudinal study, the information on a total of 95 PD patients with 5-year follow-up examinations was collected from the Parkinson's Progression Marker Initiative, 33 of which were classified into the low ALPS index group, and all others were classified into the mid-high ALPS index group based on the first tertile of the baseline ALPS index. The results of longitudinal regression indicated that there was a significant main group effect on autonomic dysfunction, as well as on activities of daily living. In addition, the low ALPS index group had faster deterioration in MDS-UPDRS part III and part II, Symbol Digit Modalities Test and Hopkins Verbal Learning Test. Path analysis showed that ALPS index acted as a significant mediator between tTau/ Aß1-42 and cognitive change in the Symbol Digit Modalities Test score at year 4 and year 5. INTERPRETATION: The ALPS index, an neuroimaging marker of glymphatic function, is correlated with PD disease severity, motor symptoms, and autonomic function, and is predictive of faster deterioration in motor symptoms and cognitive function. Additionally, glymphatic function may mediate the pathological role of toxic protein in cognitive decline. ANN NEUROL 2023;94:672-683.

Diffusion along perivascular spaces provides evidence interlinking compromised glymphatic function with aging in Parkinson's disease.

AIMS: The aim of the study was to evaluate the glymphatic function and its related factors in patients with Parkinson's disease (PD) and patients with PD of different ages using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. METHODS: Medical records and imaging data of 93 patients with idiopathic PD and 42 age- and sex-matched healthy controls (HCs) were retrospectively reviewed and analyzed. The diffusivity along the perivascular spaces, projection fibers, and association fibers were calculated on diffusion tensor imaging (DTI) to acquire the analysis along the perivascular space (ALPS) index. RESULTS: PD patients exhibited a reduced ALPS index compared with the HCs. Negative correlations between the ALPS index and clinical information including age, age at disease onset, Parkinson's disease sleep scale 2nd version (PDSS-2) scores, and history of diabetes mellitus were revealed in the PD group. Besides, a negative correlation between the ALPS index and the severity of motor symptoms was identified in the subgroup aged 65 and above, rather than in the younger ones. CONCLUSIONS: The results demonstrate that reduced ALPS index, a potential noninvasive measure of compromised glymphatic activity, is involved in the pathophysiology of PD, especially in the aged ones and those with sleep disorders.

Renin-angiotensin system blockers affect cognitive decline in Parkinson's disease: The PPMI dataset.

OBJECTIVE: To explore the potential clinical effects of renin-angiotensin system blocker (RASB, angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs)) in patients from the Parkinson's Progress Marker Initiative (PPMI) study database. METHODS: One hundred and seven untreated, newly diagnosed PD patients with hypertension, from the PPMI were included. We measured cognitive performance, biomarkers in CSF, and magnetic resonance imaging (MRI) during the five follow-up years for patients exposed or not to renal-angiotensin system blockers. Sixteen PD patients with hypertension underwent [18F]florbetaben positron emission tomography (PET) scanning. SUVRs of region of interest (ROI) were calculated and compared within different groups. RESULT: Treatment with ARBs but not ACEIs improved global cognitive function evaluated by MoCA score in PD patients with hypertension compared to other hypertensive medicines up to 5 years follow up. Specifically, ARBs improved visuospatial, memory, executive abilities, processing speed attention test scores in PD. There was no significant impact of ARBs on α-syn, tau, Aß in CSF. RASBs reduced [18F] florbetaben uptake in cortex and subcortex nuclei in the brain. CONCLUSIONS: These results show potential protective effect with ARBs in cognitive impairment of parkinson's disease with hypertension.

Distinct Bile Acid Signature in Parkinson's Disease With Mild Cognitive Impairment.

Backgrounds: Bile acid (BA) plays a crucial role in various neurodegenerative diseases, including Parkinson's disease (PD). However, no clinical evidence supports BA's potential role in patients with PD with mild cognitive impairment (PD-MCI). Objectives: This study aimed at investigating the differential BA profile between patients with PD-MCI and those with normal cognitive function (PD-NC). Methods: Ultra-high performance liquid chromatography-MS/MS was applied for BA quantitation. After between-group differences of the BA profile were addressed, orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and the area under the receiver-operating-characteristic curve (AUC-ROC) were implemented for further verification. Results: Lower levels of chenodeoxycholic acid (CDCA), cholic acid (CA), and ursodeoxycholic acid (UDCA) were significantly associated with PD-MCI (p < 0.01 for both; VIP ≈ 2.67, 1.66, and 1.26, respectively). AUC-ROC were 78.1, 74.2, and 74.5% for CDCA, CA, and UDCA, respectively. Conclusion: CA, CDCA, and UDCA might be distinct BA signatures for patients with PD-MCI.

The psoas muscle density as a predictor of postoperative complications and 30-day mortality for acute mesenteric ischemia patients.

OBJECTIVE: Low muscle mass and quality is associated with poor surgical outcomes. Psoas muscle density (PMD)is a validated surrogate for muscle quality that can be easily measured from a clinical computed tomography (CT) scan. The objective of this study was to investigate the association between PMD and short-term postoperative outcomes in patients with acute mesenteric ischemia (AMI). METHODS: From April 2006 and September 2019, the clinical data of all patients who underwent surgical intervention with a preoperative diagnosis of AMI and had preoperative non-contrast CT images available were retrospectively reviewed. PMD was measured by CT at the third lumbar vertebra. The lowest quartile of PMD for men and women in all patients was used as sex-specific cut-off values for low PMD. Univariate and multivariate analyses evaluating risk factors of postoperative complications and 30-day mortality were performed. RESULTS: The cohort consisted of 88 patients with a mean age of 58.8 ± 16.2 years, of whom 21 (23.9%) patients had low PMD based on the diagnostic cut-off values (40.5 HU for men and 28.4 HU for women), 35 (39.8%) patients developed complications within 30 days of the operation, and 10 (11.3%) patients died within 30 days of surgery. Low PMD patients had a higher risk of postoperative complications and 30-day mortality than patients without low PMD patients. In a multivariate analysis, low PMD and low psoas muscle area (PMA) were independent predictors of postoperative complications. However, only low PMD remained an independent risk factor for 30-day mortality. CONCLUSIONS: Preoperative assessment of the PMD on CT can be a practical method for identifying AMI patients at risk for postoperative complications and 30-day mortality.

Non-pharmacological treatment for Parkinson disease patients with depression: a meta-analysis of repetitive transcranial magnetic stimulation and cognitive-behavioral treatment.

Background: Nowadays, antidepressants still are the mainstay of treatment for depression in Parkinson's disease (PD) but some recent studies report that medication might aggravate motor symptoms in PD patients. This meta-analysis aims to assess the effect of non-pharmacological treatments for depression in patients with PD.Materials and Methods: Only randomized controlled trials (RCTs) were included. The participants were PD patients with comorbid depression (dPD). The interventions had the equivalent effect of non-pharmacological treatments alone compared with control(s). Scores of depression scale were selected as the primary outcome, while scores of Unified Parkinson's Disease Rating Scale part III and the incidence of side effects were the secondary outcome. The statistics were pooled and presented as weighted mean differences (WMDs), standardized mean differences (SMDs), or risk ratios (RRs) with their 95% confidence intervals (CIs).Results: Fifteen articles were eventually included; twelve studies reported on repetitive transcranial magnetic stimulation (rTMS) and three used cognitive behavioral therapy (CBT). Other interventions failed to have qualified studies. Our data indicated that both rTMS and CBT could significantly improve depression scores in a short term (SMD = -0.621, 95% CI [-0.964, -0.278]; SMD = -1.148, 95% CI [-1.498, -0.798], respectively). In addition, rTMS could alleviate motor symptom (WMD = -2.617, 95% CI [-4.183, -1.051]) and was relatively safe (RR = 1.054, 95% CI [0.698, 1.592]).Conclusion: Our data suggest that rTMS can safely alleviate depression and motor symptoms in dPD at least for a short period. Moreover, compared with clinical monitoring, CBT can improve depressive symptoms.

Alterations in intrinsic functional networks in Parkinson's disease patients with depression: A resting-state functional magnetic resonance imaging study.

AIMS: The aim of this research was to investigate the alterations in functional brain networks and to assess the relationship between depressive impairment and topological network changes in Parkinson's disease (PD) patients with depression (DPD). METHODS: Twenty-two DPD patients, 23 PD patients without depression (NDPD), and 25 matched healthy controls (HCs) were enrolled. All participants were examined by resting-state functional magnetic resonance imaging scans. Graph theoretical analysis and network-based statistic methods were used to analyze brain network topological properties and abnormal subnetworks, respectively. RESULTS: The DPD group showed significantly decreased local efficiency compared with the HC group (P = .008, FDR corrected). In nodal metrics analyses, the degree of the right inferior occipital gyrus (P = .0001, FDR corrected) was positively correlated with the Hamilton Depression Rating Scale scores in the DPD group. Meanwhile, the temporal visual cortex, including the bilateral middle temporal gyri and right inferior temporal gyrus in the HC and NDPD groups and the left posterior cingulate gyrus in the NDPD group, was defined as hub region, but not in the DPD group. Compared with the HC group, the DPD group had extensive weakening of connections between the temporal-occipital visual cortex and the prefrontal-limbic network. CONCLUSIONS: These results suggest that PD depression is associated with disruptions in the topological organization of functional brain networks, mainly involved the temporal-occipital visual cortex and the posterior cingulate gyrus and may advance our current understanding of the pathophysiological mechanisms underlying DPD.

Role of Frailty and Comorbidity Status in Predicting Morbidity and Mortality in Patients with Acute Mesenteric Ischemia.

BACKGROUND: This study was performed to determine the association of frailty and comorbidity status with postoperative morbidity and mortality in patients with acute mesenteric ischemia (AMI). METHODS: Patients diagnosed with AMI between April 2006 and September 2019 were enrolled in this study. Frailty was evaluated by sarcopenia which was diagnosed by third lumbar vertebra psoas muscle area (PMA). Comorbidity status was evaluated by the Charlson Comorbidity Index (CCI) score. Univariate and multivariate analyses evaluating the risk factors for postoperative morbidity and mortality were performed. RESULTS: Of the 174 patients, 86 were managed conservatively and 88 underwent surgery. In surgically managed patients, 39.8% developed complications within 30 days of surgery. Ten patients died within 30 days of the operation. In the univariate analyses, white blood cell >10 g/L, low PMA, CCI score ≥2, and bowel resection were associated with postoperative complications. Multivariate analysis revealed that low PMA, CCI score ≥2, and bowel resection were independent predictors of postoperative complications. CONCLUSIONS: This study demonstrated that low PMA, CCI score ≥2, and bowel resection were independent risk factors for postoperative complications in patients with AMI. Preoperative assessment of frailty using PMA and the evaluation of comorbidity status using CCI may serve as helpful tools in preoperative risk assessment and should be integrated into scoring systems for surgically treated AMI.

Gut Microbiota Altered in Mild Cognitive Impairment Compared With Normal Cognition in Sporadic Parkinson's Disease.

Background and Aim: Gut bacteria play an important role in the pathogenesis of Parkinson's disease (PD). However, the alteration of fecal microbiota in PD with cognitive impairment remains unexplored. This study aimed to explore whether the gut microbiota of patients with PD having mild cognitive impairment (PD-MCI) were different from those with PD having normal cognition (PD-NC) and from healthy controls (HC). Also, the study probed the association between altered gut microbiota and cognitive ability in patients with PD. Methods: The fecal bacteria composition and short-chain fatty acids of 13 patients with PD-MCI, 14 patients with PD-NC, and 13 healthy spouses were analyzed using 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. Results: Compared with HC, the fecal microbial diversities increased in patients with PD-MCI and PD-NC. After adjusting the influence of age, sex, body mass index, education, and constipation using the statistical method, the relative abundances of two families (Rikenellaceae and Ruminococcaceae) and four genera (Alistipes, Barnesiella, Butyricimonas, and Odoribacter) were found to be higher in the feces of the PD-MCI group compared with the other two groups. Moreover, the abundance of genus Blautia and Ruminococcus decreased obviously in the PD-MCI group compared with the PD-NC group. Further, the abundance of genera Butyricimonas, Barnesiella, Alistipes, Odoribacter, and Ruminococcus negatively correlated with cognition ability. Conclusion: Compared with HC and patients with PD-NC, the gut microbiota of patients with PD-MCI was significantly altered, particularly manifesting in enriched genera from Porphyromonadaceae family and decreased the abundance of genera Blautia and Ruminococcus.

lncRNA KCNQ1OT1 Suppresses the Inflammation and Proliferation of Vascular Smooth Muscle Cells through IκBa in Intimal Hyperplasia.

Inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the key events in intimal hyperplasia. This study aimed to explore the mechanism by which long non-coding RNA (lncRNA) KCNQ1OT1 affects VSMC inflammation and proliferation in this context. A vein graft (VG) model was established in mice to introduce intimal hyperplasia. Isolated normal VSMCs were induced with platelet-derived growth factor type BB (PDGF-BB), and the cell proliferation, migration, and secretion of inflammatory factors were determined. The results showed that KCNQ1OT1 was downregulated in the VSMCs from mice with intimal hyperplasia and in the PDGF-BB-treated VSMCs, and such downregulation of KCNQ1OT1 resulted from the increased methylation level in the KCNQ1OT1 promoter. Overexpressing KCNQ1OT1 suppressed PDFG-BB-induced VSMC proliferation, migration, and secretion of inflammatory factors. In VSMCs, KCNQ1OT1 bound to the nuclear transcription factor kappa Ba (IκBa) protein and increased the cellular IκBa level by reducing phosphorylation and promoting ubiquitination of the IκBa protein. Meanwhile, KCNQ1OT1 promoted the expression of IκBa by sponging miR-221. The effects of KCNQ1OT1 knockdown on promoting VSMC proliferation, migration, and secretion of inflammatory factors were abolished by IκBa overexpression. The roles of KCNQ1OT1 in reducing the intimal area and inhibiting IκBa expression were proved in the VG mouse model after KCNQ1OT1 overexpression. In conclusion, KCNQ1OT1 attenuated intimal hyperplasia by suppressing the inflammation and proliferation of VSMCs, in which the mechanism upregulated IκBa expression by binding to the IκBa protein and sponging miR-221.

Changes of brain structural network connection in Parkinson's disease patients with mild cognitive dysfunction: a study based on diffusion tensor imaging.

INTRODUCTION: Previous studies have found that white matter (WM) alterations might be correlated in Parkinson's disease (PD) patients with cognitive impairment. This study aimed to investigate WM structural network connectome alterations in PD patients with mild cognitive impairment (PD-MCI) and assess the relationship between cognitive impairment and structural topological network changes in PD patients. METHODS: All 31 healthy controls (HCs) and 71 PD patients (43 PD-NC and 28 PD-MCI) matched for age, sex and education underwent 3.0 T MRI and diffusion tensor imaging (DTI) scan. Graph theoretical analyses and network-based statistical (NBS) analyses were performed to identify the structural WM networks and subnetwork changes in PD-MCI. RESULTS: PD-MCI patients showed significantly decreased global efficiency (Eglob) and increased shortest path length (Lp) compared with the HC group. Several nodal efficiencies showed significant differences in multiple brain regions among the three groups. The nodal efficiency of the orbitofrontal part was closely related to the overall cognitive ability and multiple sub-cognitive domains. Moreover, NBS analyses identified eight one-connect subnetworks, three two-connect subnetworks and two multi-connect subnetworks with reduced connectivity that characterizes the WM structural organization in PD-MCI patients. The two multi-connect subnetworks were located on the bilateral lobe, and both were centered on the orbitofrontal part. CONCLUSIONS: This study provided new evidence that PD with cognitive dysfunction is associated with WM structural alterations. The nodal efficiency and sub-network analyses focusing on the orbitofrontal part might provide new ideas to explore the physiological mechanism of PD-MCI.

Macrophage Migration Inhibitory Factor Mediates Neuroprotective Effects by Regulating Inflammation, Apoptosis and Autophagy in Parkinson's Disease.

The influence of neuroinflammation in the development and progression of Parkinson's disease (PD) remains unknown. Macrophage migration inhibitory factor (MIF) is a multipotent and key cytokine involved in the pathogenesis of acute and chronic inflammatory and immune disorders. The aim of this study was to investigate the neuroprotective effects mediated by MIF in PD. Cellular apoptosis was measured by RT-qPCR analysis, fluorescence-activated cell sorting (FACS) analysis and western blotting. JC-1 staining was used to analyze the mitochondrial membrane potential (MMP). The formation of autophagosomes was detected by western blot analysis. Autophagic flux was assessed by tandem mRFP-GFP-LC3 fluorescence microscopy. Expression of MIF, cleaved-PARP and LC3B-II was increased significantly in both acute and chronic PD animal models. MIF was positively associated with IL-10 (P < 0.001), but inversely with TNF-α (P < 0.05). The PD cells (1 mM MPP+ treated group) showed an increase in early-apoptotic cells by FACS. Upregulating MIF expression resulted in a lower concentration of cleaved-PARP than the control group (P < 0.001). The MMP was higher in the MIF upregulated group than in the MIF knockdown group (P < 0.001). Upregulating MIF expression resulted in a higher concentration of LC3B-II than the control group (P < 0.001). Finally, LC3 puncta were markedly increased in the MIF upregulated group and in the MIF + MPP+ group. This study indicates that MIF mediates a neuroprotective effect via suppressing inflammatory responses, inhibiting apoptosis and inducing autophagy in PD.

Interfering histone deacetylase 4 inhibits the proliferation of vascular smooth muscle cells via regulating MEG3/miR-125a-5p/IRF1.

In this study, we investigated the role ofhistone deacetylase 4 (HDAC4) and MEG3/miR-125a-5p/interferonregulatoryfactor 1 (IRF1) on vascular smooth muscle cell (VSMCs)proliferation. Platelet derived growth factor (PDGF)-BB was used toinduce the proliferation and migration of VSMCs. The expressionsof MEG3, miR-125a-5p, HDAC4 and IRF1in VSMCs were detectedby qRT-PCR and western blot, respectively. ChIP assay was usedto determine the relationship between MEG3 and HDAC4. Doubleluciferase reporter assay was used to test the regulation betweenmiR-125-5p and IRF1. Results showed that PDGF-BB decreasedthe expression of MEG3 and IRF1, while increased the expressionof miR-125a-5p and HDAC4. In addition, HDAC4 knockdowninhibited the proliferation and migration of VSMCs via upregulatingMEG3 and downregulating miR-125a-5p. MiR-125a-5p inhibitorcould repress the proliferation and migration of VSMCs andalleviate intimal hyperplasia (IH) by directly upregulating IRF1expression. These results suggested that HDAC4 interferenceinhibited PDGF-BB-induced VSMCs proliferation via regulatingMEG3/miR-125a-5p/IRF1 axis, and then alleviated IH.

Determination of Risk Factors and Establishment of a Prediction Model for Immediate Technical Failure during Endovascular Treatment of Femoropopliteal Occlusive Disease.

BACKGROUND: For long femoropopliteal occlusive lesions, the immediate technical failure (ITF) of endovascular treatment (EVT) is relatively high. Therefore, this study aims to reveal risk factors and establish a prediction model of ITF of EVT in femoropopliteal occlusive disease (FPOD) patients based on preoperative clinical date that may be helpful to the clinical procedures. METHODS: A retrospective analysis of 1,563 FPOD patients who underwent above-the-knee EVT was undertaken. Univariate analysis with chi-squared test was used to screen risk factors from preoperative clinical data. Multivariable analysis with logistic regression was used to generate a model for predicting the ITF rate of EVT, which was evaluated through the receiver operating characteristic curve and another independent cohort of 242 FPOD patients. RESULTS: Risk factors for ITF during EVT in FPOD included age (>80 years, X1), the absence of diabetes mellitus (X2), low-density lipoprotein (>160 mg/dL, X3), lesion calcification (X4), lesion length (>20 cm, X5), ostial occlusion of superficial femoral artery (SFA) (X6), and SFA lesion involving the popliteal artery (X7). A logistic regression model was established based on the equation: -6.504 + 1.236X1 + 0.945X2 + 1.406X3 + 1.136X4 + 1.059X5 + 2.307X6 + 2.194X7. Scores were given to risk factors as follows: X1 (yes = 12, no = 0), X2 (yes = 9, no = 0), X3 (yes = 14, no = 0), X4 (yes = 11, no = 0), X5 (yes = 11, no = 0), X6 (yes = 23, no = 0), and X7 (yes = 22, no = 0). We determined that the optimal comprehensive score for predicting EVT failure was 39, with a sensitivity of 0.847 and a specificity of 0.8. Among these 242 peripheral arterial disease patients, 12 of 14 patients who had failed EVT had a comprehensive score of >39. CONCLUSIONS: We identified a number of risk factors of ITF during the above-the-knee EVT and established a prediction model that may be used for guidance in clinical practice.

[The significance of calcification in the thyroid papillary carcinoma].

OBJECTIVE: To study the significance of calcification in the thyroid papillary carcinoma. METHOD: Retrospectively analyze 88 cases of thyroid papillary carcinoma. RESULT: There was no association between calcification with age,TSH and TNM. But calcification was related to the size of tumor (P < 0.05). In addition, the level of TSH has no relationship with the size of tumor. CONCLUSION: Calcification especially microcalcification may have significant relationship with thyroid papillary carcinoma and be directly related to the size of tumor. The larger size of tumor implies the higher possibility of calcification.