Pharmacological and Behavioral Interventions for Fatigue in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aims to evaluate pharmacological and behavioral interventions for the treatment of fatigue in Parkinson's disease (PD) patients. METHODS: We systematically searched PubMed, PsycINFO, Web of Science, EMBASE, CNKI, Wan fang, and VIP up to July 31, 2022. We used Revman 5.3 software for the meta-analysis. The outcomes included Fatigue Severity Scale (FSS) and Parkinson's Fatigue Scale (PFS). The mean difference (MD) and 95% confidence intervals (CI) were collected or calculated. RESULTS: Thirteen randomized controlled trials (RCTs) with a total of 1758 patients were included. The meta-analysis showed that current clinical treatments reduced FSS (MD: -1.60, 95% CI: -3.14 to -0.05) and PFS (MD: -0.61, 95% CI: -1.17 to -0.05) in patients with PD. Subgroup meta-analysis showed that: (1) neither pharmacological interventions nor behavioral interventions reduced FSS in PD patients; (2) dopaminergic drugs dose-dependently significantly reduced the PFS in patients with PD; (3) behavioral interventions have an almost significant effect (MD: -6.69, 95% CI: -13.71 to 0.33, P = 0.06, I2 = 74%) on alleviating PFS in PD patients; (4) vestibular rehabilitation training significantly reduced the PFS in patients with PD. CONCLUSIONS: Current clinical treatments alleviate fatigue in PD patients. Dopaminergic drugs may act a stronger effect than amphetamines. Behavioral interventions, especially vestibular rehabilitation training, may be a promising way for the treatment of fatigue in patients with PD though further evidence is still needed.

Research on Traditional Chinese Medicine: Domain Knowledge Graph Completion and Quality Evaluation.

BACKGROUND: Knowledge graphs (KGs) can integrate domain knowledge into a traditional Chinese medicine (TCM) intelligent syndrome differentiation model. However, the quality of current KGs in the TCM domain varies greatly, related to the lack of knowledge graph completion (KGC) and evaluation methods. OBJECTIVE: This study aims to investigate KGC and evaluation methods tailored for TCM domain knowledge. METHODS: In the KGC phase, according to the characteristics of TCM domain knowledge, we proposed a 3-step "entity-ontology-path" completion approach. This approach uses path reasoning, ontology rule reasoning, and association rules. In the KGC quality evaluation phase, we proposed a 3-dimensional evaluation framework that encompasses completeness, accuracy, and usability, using quantitative metrics such as complex network analysis, ontology reasoning, and graph representation. Furthermore, we compared the impact of different graph representation models on KG usability. RESULTS: In the KGC phase, 52, 107, 27, and 479 triples were added by outlier analysis, rule-based reasoning, association rules, and path-based reasoning, respectively. In addition, rule-based reasoning identified 14 contradictory triples. In the KGC quality evaluation phase, in terms of completeness, KG had higher density and lower sparsity after completion, and there were no contradictory rules within the KG. In terms of accuracy, KG after completion was more consistent with prior knowledge. In terms of usability, the mean reciprocal ranking, mean rank, and hit rate of the first N tail entities predicted by the model (Hits@N) of the TransE, RotatE, DistMult, and ComplEx graph representation models all showed improvement after KGC. Among them, the RotatE model achieved the best representation. CONCLUSIONS: The 3-step completion approach can effectively improve the completeness, accuracy, and availability of KGs, and the 3-dimensional evaluation framework can be used for comprehensive KGC evaluation. In the TCM field, the RotatE model performed better at KG representation.

A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid ß accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.

Microscopic Mechanism of CO2 Displacement Oil in Different Pore Throat Radius Segments of Tight Sandstone Reservoirs.

The micropore structure of tight sandstone affects the efficiency of CO2 displacement of crude oil. As the pressure changes, the oil displacement efficiency (E d) in segments with different pore radii changes, and the asphaltene precipitation in the pores causes alterations in the pore structure and wettability, which constrain E d. Ten samples of tight sandstone from the Yanchang Formation in the Ordos Basin were selected for this study. A variety of methods, including X-ray diffraction (XRD), casting thin sections (CTS), scanning electron microscopy (SEM), high-pressure mercury intrusion (HPMI), CT scanning, and nuclear magnetic resonance (NMR) combined with CO2 displacement, were used to study the efficiency of crude oil utilization and the amount of asphaltene deposited at different pore-throat radii, and then the impacts of pressure, pore structure, and wettability changes on E d were discussed. The findings indicate that samples have three types: macropore-fine throats (MF), medium pore-tiny throats (MT), and small pore-microthroats (SM). The MT exhibits a favorable configuration. The pore-throat radius of each sample can be divided into two segments, namely, large pore segments (PL) and small pore segments (PS), and the PL has a significant E d. The E d of the MF-type PS is constrained by pressure. The E d of PL is significantly affected by the pressure sensitivity for the MT, while the E d of PL for the SM structure is more affected by pressure. Changes in wettability and the precipitation of asphaltene are the results of the reaction between crude oil and CO2. In the MF, asphaltene precipitates from the PL, while in the MT and SM, asphaltene precipitates both from the PL and PS. The amount of asphaltene precipitation strongly affects the E d in PS. The oil wettability increases more obviously with better pore-throat configurations. This study offers a reference and foundational understanding for evaluating CO2 displacement in tight sandstone reservoirs.

Pore- and Core-Scale Recovery Performance of Consortium Bacteria from Low-Permeability Reservoir.

Performance evaluation of microorganisms that have emulsifying and degrading effects on crude oil has been extensively conducted in the laboratory. However, the ultimate goal of microbial enhanced oil recovery is field application, so the pilot simulation experiments are crucial. In this study, a micro-visualization model and the real cores were chosen to investigate the actual recovery efficiency and the mechanism of the consortium bacteria B-ALL, which has been proven to have good emulsification and degradation effects in lab studies in porous media. At the same time, the cast thin sections and rate-controlled porosimetry were combined to analyze the pore throat structure of the displacement core. It was found that the recovery efficiency was positively correlated with the microbial injection volume as well as the incubation time. For the microscopic model with high pores and high permeability, the efficiency of secondary water flooding can be increased by 44.77% after six days of incubation with two pore volume microbes. For the real tight cores, the maximum secondary water flooding efficiency under the same condition was 6.98%. Through visual modeling, microorganisms increase the oil washing efficiency mainly by emulsification and changing the wettability. The generated oil droplets will play a role in plugging and improving the wave efficiency. However, tight reservoirs have the characteristics of large pores and small throats, and curved and necking throats are developed, greatly reducing permeability. The microbial recovery efficiency was lower under shorter cultivation times. This study provides a practical basis for the application of consortium bacteria in tight oil fields to enhance recovery.

Association between systemic lupus erythematosus and disruption of gut microbiota: a meta-analysis.

OBJECTIVE: Recent studies reported that SLE is characterised by altered interactions between the microbiome and immune system. We performed a meta-analysis of publications on this topic. METHODS: Case-control studies that compared patients with SLE and healthy controls (HCs) and determined the diversity of the gut microbiota and the abundance of different microbes were examined. Stata/MP V.16 was used for the meta-analysis. A Bonferroni correction for multiple tests was used to reduce the likelihood of false-positive results. RESULTS: We included 11 case-control studies that examined 373 patients with SLE and 1288 HCs. These studies were performed in five countries and nine cities. Compared with HCs, patients with SLE had gut microbiota with lower Shannon-Wiener diversity index (weighted mean difference=-0.22, 95% CI -0.32 to -0.13, p<0.001) and lower Chao1 richness (standardised mean difference (SMD)=-0.62, 95% CI -1.04 to -0.21, p=0.003). Patients with SLE had lower abundance of Ruminococcaceae (SMD = -0.49, 95% CI -0.84 to -0.15,p=0.005), but greater abundance of Enterobacteriaceae (SMD=0.45, 95% CI 0.01 to 0.89, p=0.045) and Enterococcaceae (SMD=0.53, 95% CI 0.05 to 1.01, p=0.03). However, only the results for Ruminococcaceae passed the Bonferroni correction (p=0.0071). The two groups had no significant differences in Lachnospiraceae and Bacteroides (both p>0.05). Patients with SLE who used high doses of glucocorticoids had altered gut microbiota based on the Chao1 species diversity estimator, and hydroxychloroquine use appeared to reduce the abundance of Enterobacteriaceae. CONCLUSIONS: Patients with SLE have imbalanced gut microbiota, with a decrease in beneficial bacteria and an increase in harmful bacteria. Drugs used to treat SLE may also alter the gut microbiota of these patients.