[Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review].

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Apolipoprotein E Genotype Contributes to Motor Progression in Parkinson's Disease.

BACKGROUND: Emerging evidence indicates that the apolipoprotein E (APOE) ε4 exacerbates α-synuclein pathology. OBJECTIVE: To determine whether APOE ε4 contributes to motor progression in early Parkinson's disease (PD). METHODS: Longitudinal data were obtained from 384 patients with PD divided into APOE ε4 carriers (n = 85) and noncarriers (n = 299) in the Parkinson's Progression Marker Initiative. Participants underwent yearly motor assessments over a mean follow-up period of 78.9 months. Repeated measures and linear mixed models were used to test the effects of APOE ε4. RESULTS: The motor progression was significantly more rapid in patients with PD carrying APOE ε4 than in noncarriers (ß = 0.283, P = 0.026, 95% confidence interval: 0.033-0.532). Through subgroup analysis, we found that the effect of APOE ε4 was significant only in patients with high amyloid ß burden (ß = 0.761, P < 0.001, 95% confidence interval: 0.0356-1.167). CONCLUSIONS: APOE ε4 may be associated with rapid motor progression in PD. © 2021 International Parkinson and Movement Disorder Society.

Different patterns of exosomal α-synuclein between Parkinson's disease and probable rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. METHODS: In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. RESULTS: It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. CONCLUSIONS: Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.

Potential Chemoprevention of Paeoniflorin in Colitis-Associated Colorectal Cancer by Network Pharmacology, Molecular Docking, and In Vivo Experiment.

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

From inflammasome to Parkinson's disease: Does the NLRP3 inflammasome facilitate exosome secretion and exosomal alpha-synuclein transmission in Parkinson's disease?

A pivotal neuropathological manifestation of synucleinopathies, like Parkinson's disease (PD), is the aggregation of α-synuclein. In a recent cell-to-cell transmission model of α-synuclein, α-synuclein propagation was demonstrated to resemble that of prion proteins in the central nervous system. Furthermore, exosomes, as biomolecule carriers, have been shown to transmit α-synuclein from neuron to neuron. However, the mechanisms underlying exosomal α-synuclein transmission have not been well understood. The NLR family pyrin domain containing 3 protein (NLRP3) inflammasome activation in microglia, and the subsequent release of proinflammatory cytokines, are two crucial pathological events involved in neuroinflammation and PD progression. Research has revealed that the NLRP3 inflammasome may facilitate the secretion of extracellular vesicles, as well as exosomal transmission of proteins like aggregated α-synuclein. However, only a few reports have evaluated these pathogenic mechanisms. Herein we evaluate for the first time the current evidence for the involvement of the NLRP3 inflammasome in microvesicle generation by microglial cells, and the various mechanisms regarding the production, shedding, and content of exosomes in relation to α-synuclein transmission from neuron to neuron. Furthermore, we propose a model of microglial NLRP3 inflammasome-dependent exosome secretion and exosomal α-synuclein transmission in PD. This knowledge may lead to the identification of novel potential targets for drug development and stimulate further research in PD.

Parkinson's Disease in Teneurin Transmembrane Protein 4 (TENM4) Mutation Carriers.

INTRODUCTION: Mutations in the teneurin transmembrane protein 4 (TENM4) gene, known to be involved in neuropsychiatric disorders, have been identified in three pedigree of essential tremor (ET) from Spain. ET has overlapping clinical manifestations and epidemiological symptoms with Parkinson's disease (PD), suggesting these two disorders may reflect common genetic risk factors. In this study, we investigated clinical and genetic manifestations in four unrelated pedigrees with both ET and PD in which TENM4 variants were identified. METHODS: We subsequently explored whether TENM4 variants contributed to the risk of developing PD. The frequency of TENM4 variants was evaluated from four PD pedigrees and other 407 subjects. RESULTS: The results revealed 12 different novel heterozygous variants, all at low frequency. A clear general enrichment of TENM4 variants was detected in early onset PD patients (p < 0.001, OR = 5.264, 95% CI = 1.957-14.158). CONCLUSION: The results indicate that rare TENM4 variants may be associated with an increased risk of PD.

MRI-visible perivascular spaces are associated with cerebrospinal fluid biomarkers in Parkinson's disease.

Perivascular spaces in the brain have been known to communicate with cerebrospinal fluid and contribute to waste clearance in animal models. In this study, we sought to determine the association between MRI-visible enlarged perivascular spaces (EPVS) and disease markers in Parkinson's disease (PD). We obtained longitudinal data from 245 patients with PD and 98 healthy controls from the Parkinson's Progression Marker Initiative. Two trained neurologists performed visual ratings on T2-weighted images to characterize EPVS in the centrum semiovale (CSO), the basal ganglia (BG) and the midbrain. We found that a greater proportion of patients with PD had low grade BG-EPVS relative to healthy controls. In patients with PD, lower grade of BG-EPVS and CSO-EPVS predicted lower CSF α-synuclein and t-tau. Lower grade of BG-EPVS were also associated with accelerated Hoehn &Yahr stage progression in patients with baseline stage 1. BG-EPVS might be a valuable predictor of disease progression.

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease.

BACKGROUND: Excessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson's disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear. OBJECTIVE: To evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients. METHODS: We enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis. Spearman analysis was used to test the correlation of MRI-visible EPVS with clinical characteristics of patients. RESULTS: iRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Higher CSO-EPVS and BS-EPVS burdens were independent risk factors for iRBD. Furthermore, higher CSO-EPVS and SN-EPVS burdens were positively correlated with the severity of clinical symptom in iRBD patients, and higher BG-EPVS burden was positively correlated with the severity of cognitive impairment in PD patients. CONCLUSION: iRBD and PD patients have different MRI-visible EPVS burdens, which may be related with a compensatory mechanism in glymphatic system. Lower MRI-visible EPVS burden in PD patients may be a manifestation of severe brain waste drainage dysfunction. These findings shed light on the pathophysiologic relationship between iRBD and PD with respect to neuroimaging marker of PD.

Mechanical Thrombectomy Outcome Predictors in Stroke Patients with M2 Occlusion: A Single-Center Retrospective Study.

BACKGROUND: Mechanical thrombectomy (MT) has demonstrated benefit in patients with acute ischemic stroke due to proximal large-vessel occlusion. However, it is unclear whether these results can be extrapolated to patients with an occlusion of the second segment (M2) of the middle cerebral artery (MCA). We sought to study outcomes in patients with M2 occlusion treated with MT and to better understand clinical predictors of these outcomes. METHODS: We performed a single-center retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent stent retriever MT. We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: Thirty-seven patients were included in the analysis (median admission National Institutes of Health Stroke Scale [NIHSS] score, 15 [12-19], mean age 74 [67-80] years, 48.6% women). Good clinical outcome at 3 months (modified Rankin Scale ≤2) was achieved in 48.6% of patients. Baseline NIHSS was a predictor of clinical outcomes, based on modified Rankin Scale distribution at 3 months after MT (P = 0.015, odds ratio 1.63, 95% confidence interval 1.01-2.43). CONCLUSIONS: The results of our single-institution experience suggest that MT-based endovascular therapy for M2 occlusions is safe and effective. Baseline NIHSS was a predictor of outcomes in patients treated with MT for M2 segment occlusion of the MCA.

Mechanical Thrombectomy Using Solitaire in Acute Ischemic Stroke Patients with Vertebrobasilar Occlusion: A Prospective Observational Study.

BACKGROUND: The safety and effectiveness of endovascular mechanical thrombectomy in patients with acute vertebrobasilar occlusion (VBO) are debatable and undergoing evaluation. We report the clinical outcome and prognostic factors in a prospective cohort of acute ischemic stroke patients with VBO. METHODS: In total, 48 consecutive patients with acute VBO underwent mechanical thrombectomy using Solitaire. We analyzed clinical and imaging data and searched for predictors of good clinical outcome (modified Rankin scale score: 0-3). RESULTS: The median prethrombectomy National Institutes of Health Stroke Scale score was 22.0. The median duration from symptom onset to recanalization was 493.5 minutes. A total of 35.4% of the patients received rescue therapy. Recanalization (modified Thrombolysis In Cerebral Infarction: 2b-3) was successful in all patients. Clinically relevant intracranial hemorrhage was observed in 2 patients. After 90 days, good outcomes were obtained in 27 patients. The baseline National Institutes of Health Stroke Scale score, posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS), anesthesia type, and posterior communicating artery (PComA) patency were significantly associated with outcomes at 90 days in univariate analysis. Multivariate logistic regression indicated that high pc-ASPECTS at admission and PComA patency were independent predictors of good outcome at 90 days. CONCLUSIONS: Up to 60.4% of the patients reached good outcomes after endovascular treatment and 35.4% of the patients received rescue therapy, suggesting that mechanical thrombectomy using Solitaire in patients with stroke with VBO is safe and effective and that rescue therapy is readily required and employed. High baseline pc-ASPECTS and PComA patency were associated with better outcomes after thrombectomy in these patients.

Study of GCH1 and TH genes in Chinese patients with Parkinson's disease.

Whole-exome sequencing of Parkinson's disease (PD) patients has revealed that the frequency of GTP-cyclohydrolase I (GCH1) variants was significantly higher in patients than in controls. GCH1 rs11158026 was also found to increase the risk of PD. To investigate genetic contribution of dopa-responsive dystonia-related genes to PD, GCH1, and tyrosine hydroxylase (TH) were tested in PD patients. A total of 859 study subjects comprising 421 patients with PD and 438 controls were recruited. For GCH1 gene, one known variant (c.239G > A, p.S80N) was detected in a patient who was diagnosed with PD clinically. In TH, 3 heterozygous variants, c.1495G > A (p. V499M, rs1800033), c.334 A > G (p.V112M, rs6356), and c.813 G > A (p. K271K, rs6357), were identified. After stratification by age, the frequency of rs6356G allele was significantly lower (p = 0.041) for the late-onset PD group than controls. Our results indicate that to analyze the relationship between dopa-responsive dystonia-related genes and PD, it is important to screen GCH1 and test rs6356 of TH in a larger sample.

Disgust responding in obsessive-compulsive disorder with and without contamination washing symptoms / 中国心理卫生杂志

Objective:The present study aim to explore the difference and characteristics of disgust in obsessive-compulsive disorder(OCD) with/without contamination washing symptoms,adding to the growing literature on the heterogeneity and clinical treatment of OCD.Methods:Totally 66 patients with OCD meeting the criteria of International Statistical Classification of Diseases and Related Health Problems,Tenth Revision (ICD-10) and 51 healthy controls matched with gender,age and level of education were recruited.All patients were divided into two subgroups namely washing symptoms group(n =26) and other symptoms group(n =40) based on the contamination washing symptoms.Participants respectively completed the lexical decision task.The results of the tasks were indicators reflecting the disgust feelings,including the accuracy,reaction time to core disgust words,moral disgust words,neutral words,and the rating intensity of disgust provoked by all of the words.Results:The reaction time for core disgust words[(723 ± 89)ms,(746 ± 95) ms vs.(676 ± 96) ms] and moral disgust words[(772 ± 98)ms,(796± 92)ms vs.(723 ± 94)ms] were longer in both group of patients with OCD than in healthy controls.The patients also rated higher degree of disgust for core disgust words[(6.7 ± 1.5),(6.9 ± 1.6)vs.(5.8 ± 1.7)]and moral disgust words [(6.8 ± 1.7),(7.2 ± 1.3)vs.(6.3 ± 1.5)] than healthy controls (Ps ＜0.05).But there were no difference existed between patients with and without contamination washing symptoms on the results of lexical decision task(Ps ＜0.05).Conclusion:It shows that patients with OCD tend to experience intense disgust feelings,and there is no difference between contamination washing symptoms and other symptoms on disgust.These findings suggest that intense disgust feelings may play a role on the etiology and maintenance of OCD,and reducing disgust could be a potential approach for OCD treatment.