Discovery of cinnamamide/ester triazole hybrids as potential treatment for Alzheimer's disease.

Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aß-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aß toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aß deposition in Aß1-42-injured mice. Mechanistically, the compound regulated APP processing by promoting the ADAM10-associated nonamyloidogenic signaling and inhibiting the BACE1-mediated amyloidogenic pathway. Moreover, it suppressed intracellular AChE activity and tau phosphorylation. Therefore, compound 4j may be a promising multitargeted active molecule against AD.

Knowledge Mapping of Inflammasome and Pyroptosis in Stroke: A Bibliometric Analysis (2007-2023).

BACKGROUND: Stroke is a major contributor to disability and death worldwide. Studies have demonstrated that inflammasome/pyroptosis and its mediated inflammatory response are important factors aggravating brain injury after stroke. We aimed to investigate and map the knowledge structure and global trends on inflam- masome/pyroptosis in stroke. METHODS: All relevant documents were obtained from the Web of Science on 5 June 2023. Bibliometric visualization diagrams were created using VOSviewer and CiteSpace. Excel was used for statistical analysis and drawing graphs. RESULTS: A total of 1106 publications were included, with more articles published each year, especially since 2014. China (740 papers), Zhejiang University (57 papers), Wang J (25 papers), and the Journal of Neuroinflammation (45 papers) were the most productive countries, institutions, authors, and journals, respectively. The United States was the country with highest centrality (0.56) and total link strength (171), and all of the top 10 institutions were in China. China and the U.S. cooperated closely. The centralities of the top 10 authors were all lower than 0.01; no leader has yet emerged in this field. "NLRP3 inflammasome" ranked first with 447 occurrences among 2136 keywords, of which 56 terms appeared more than 10 times when categorized into four clusters: cluster 1 (inflammation), cluster 2 (pyroptosis), cluster 3 (NLRP3 inflammasome), and cluster 4 (neuroinflammation). The studies focused on the mechanisms of inflammasome/pyroptosis in stroke were mainly limited to cell and animal experiments. CONCLUSION: Interest in inflammasome/pyroptosis in stroke is progressively increasing. The NLRP3 inflammasome is the most extensively studied and has been a research hotspot. The mechanisms of cell death in stroke are complex and future studies are needed to strengthen the clinical research on the relationship between pyroptosis-related processes and stroke, determine at which stage NLRP3 inflammasome activation, and clarify the detailed mechanism of NLRP3 in stroke.

Identification of Montelukast as flavivirus NS2B-NS3 protease inhibitor by inverse virtual screening and experimental validation.

Flavivirus, such as Dengue Virus (DENV) and Zika virus (ZIKV), infects millions of people and cause the death of thousands of people every year. Despite many efforts, there is no approved anti-flaviviral treatment available. In particular, some antiflavivirus compounds were investigated the cellular activities of DENV and ZIKV, but lacking the exploration of specific target enzyme, thereby resulting in the hindrance of structure-based drug design. One example is Montlukast, which was found to inhibit the replicon replication in DENV and ZIKV infected cells, with EC50 values as 1.03 µM (DENV) and 1.14 µM (ZIKV), while the underlying mechanism remains unclear. In our study, the inhibitory mechanisms of Montelukast against the replicon replication of DENV and ZIKV infected cells were studied by using in silico approaches including inverse virtual screening (IVS), molecular dynamics (MD) simulations and binding free energy calculation, and validated through in vitro protease assay, confirming Montelukast could bind to NS2B-NS3 proteases of DENV and ZIKV as a competitive inhibitor (IC50 for DENV: 25.65 µM, for ZIKV: 15.57 µM). Moreover, Montelukast has no potential off-target effect on NS2B-NS3 protease from thrombin and trypsin inhibitory assay. Overall, Montelukast may be used as a potential candidate to block NS2B-NS3 protease as well as lead for structural modification.

Discovery of highly potent DENV NS2B-NS3 covalent inhibitors containing a phenoxymethylphenyl residue.

Dengue virus (DENV) has developed rapidly in the past few decades and has been becoming the most widespread arbovirus in the world. The vital role of NS2B-NS3 in virus replication and maturation of relevant proteins makes it the most promising target for anti-DENV drug discovery, although none of NS2B-NS3 inhibitors have been approved for the market so far. In this study, potent NS2B-NS3 covalent inhibitors were discovered via chemical modification of a published covalent inhibitor WSL-01 (IC50 = 129 nM), yielding promising analogs WSL-75 and WSL-84 (IC50 = 24.8 nM and IC50 = 32.89 nM, respectively) with more than 10-fold increased enzymatic activities compared to the lead compound, and no evident cellular toxicity was observed. Further comprehensive structure-activity relationship analysis through covalent docking and molecular dynamics simulation provides informative understanding of the binding modes of covalent inhibitors targeting NS2B-NS3, which would be beneficial for novel NS2B-NS3 inhibitory development.

Synthetic analogues of memantine as neuroprotective and influenza viral inhibitors: in vitro and physicochemical studies.

Drug compounds including memantine moieties are an important group of biologically active agents for different pathologies, including the Alzheimer's disease. In the present study, a series of memantine derivatives incorporating amino acid residues have been synthesized and their neuroprotective in vitro evaluation in respect of the Alzheimer's disease, involving the effects on the resistance to Aß toxicity, excitotoxicity, oxidative stress, hypoxia, and neuroinflammation has been studied. The cytotoxicities of the compounds were detected by CPE assay. TC50 and IC50 were determined using Reed and Muench method. Solubility and distribution were measured using a shake-flask method. Permeability of the compounds was studied using Franz diffusion cell and Permeapad™ barrier. These compounds displayed apparent multi-neuroprotective effects against copper-triggered Aß toxicity, glutamate-induced excitotoxicity, and oxidative and hypoxic injuries. They also showed the ability to inhibit the inflammatory cytokine release from the activated microglia and potential anti-neuroinflammatory effects. Especially, two most promising compounds H-4-F-Phe-memantine and H-Tyr-memantine demonstrated the equivalent functional bioactivities in comparison with the positive control memantine hydrochloride. Higher solubility in muriatic buffer than in phosphate buffer was detected. The distribution coefficients showed the optimal lipophilicity for compounds. The presented results propose new class of memantine derivatives as potential drug compounds. Based on the experimental results, the correlations have been obtained between the biological, physicochemical parameters and structural descriptors. The correlation equations have been proposed to predict the properties of new memantine derivatives knowing only the structural formula.

Old drug new tricks: Chlorhexidine acts as a potential allosteric inhibitor toward PAK1.

This paper describes the identification of chlorhexidine, an agent commonly used in clinical as a novel potential allosteric inhibitor of PAK1. In cellular assays, chlorhexidine showed a good inhibitory profile, and its inhibitory profile was even better than IPA-3, a well-known allosteric inhibitor. In pharmacology experiments, chlorhexidine successfully inhibited the relief of PAK1 dimer and inhibited the activation of PAK1. Our findings offer an insight for the new drug development of PAK1 inhibitor. We also provide a possible explanation for the phenomenon that the application of the chlorhexidine in peritoneal lavage inhibited the development of tumor.

Two Histidines in an α-Helix: A Rigid Co2+ -Binding Motif for PCS Measurements by NMR Spectroscopy.

Pseudocontact shifts (PCS) generated by paramagnetic metal ions present valuable long-range information in the study of protein structural biology by nuclear magnetic resonance (NMR) spectroscopy. Faithful interpretation of PCSs, however, requires complete immobilization of the metal ion relative to the protein, which is difficult to achieve with synthetic metal tags. We show that two histidine residues in sequential turns of an α-helix provide a binding site for a Co2+ ion, which positions the metal ion in a uniquely well-defined and predictable location. Exchange between the bound and free cobalt is slow on the timescale defined by chemical shifts, but the NMR resonance assignments are nonetheless readily transferred from the diamagnetic to the paramagnetic NMR spectrum by an Iz Sz -exchange experiment. The double-histidine-Co2+ motif offers a straightforward, inexpensive, and convenient way of generating precision PCSs in proteins.

Luteolin Inhibits Fibrillary ß-Amyloid1-40-Induced Inflammation in a Human Blood-Brain Barrier Model by Suppressing the p38 MAPK-Mediated NF-κB Signaling Pathways.

Amyloid-ß peptides (Aß) exist in several forms and are known as key modulators of Alzheimer's disease (AD). Fibrillary Aß (fAß) has been found to disrupt the blood-brain barrier (BBB) by triggering and promoting inflammation. In this study, luteolin, a naturally occurring flavonoid that has shown beneficial properties in the central nervous system, was evaluated as a potential agent to preserve barrier function and inhibit inflammatory responses at the BBB that was injured by fAß1-40. We established an in vitro BBB model by co-culturing human brain microvascular endothelial cells (hBMECs) and human astrocytes (hAs) under fAß1-40-damaged conditions and investigated the effect of luteolin by analyzing cellular toxicity, barrier function, cytokine production and inflammation-related intracellular signaling pathways. Our results demonstrated that, in cells injured by fAß1-40, luteolin increased cell viability of hBMECs and hAs. The cytoprotection of the co-culture against the damage induced by fAß1-40 was also increased at both the apical and basolateral sides. Luteolin protected the barrier function by preserving transendothelial electrical resistance and relieving aggravated permeability in the human BBB model after being exposed to fAß1-40. Moreover, in both the apical and basolateral sides of the co-culture, luteolin reduced fAß1-40-induced inflammatory mediator and cytokine production, including cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin 1 ß (IL-1ß), interleukin 6 (IL-6), and interleukin 8 (IL-8), however it did not show sufficient effects on scavenging intracellular reactive oxygen species (ROS) in hBMECs and hAs. The mechanism of BBB protection against fAß1-40-induced injury may be related to the regulation of inflammatory signal transduction, which involves inhibition of p38 mitogen-activated protein kinase (MAPK) activation, downregulation of phosphorylated inhibitory κB kinase (phosphor-IKK) levels, relief of inhibitory κB α (IκBα) degradation, blockage of nuclear factor κB (NF-κB) p65 nuclear translocation, and reduction of the release of inflammatory cytokines. Moreover, the employment of p38 MAPK and NF-κB inhibitors reversed luteolin-mediated barrier function and cytokine release. Taken together, luteolin may serve as a potential therapeutic agent for BBB protection by inhibiting inflammation following fAß1-40-induced injury.

The Prescription trends and dosing appropriateness analysis of novel oral anticoagulants in ischemic stroke patients: a retrospective study of 9 cities in China.

Background: Novel oral anticoagulants (NOACs) have been recommended by guidelines as the first-line drugs for preventing cardiogenic stroke. We aimed to provide an overview of the prescription trends and dosing appropriateness of NOACs in China. Methods: We conducted a retrospective analysis of NOAC prescriptions using the Hospital Prescription Analysis Cooperation Project data from 2016 to 2022. Various patient features, such as gender, age, city, year, source, department visited, original diagnosis, dosing, cost, and insurance type, were collected and analyzed to examine the trends and dosing appropriateness of NOAC usage in ischemic stroke patients. Results: 62,014 NOAC prescriptions were analyzed, including 16,602 for dabigatran, 45,253 for rivaroxaban, and 159 for apixaban. 85.14% of the patients were aged 65 or above, and tertiary hospitals accounted for 95.97% of NOAC prescriptions. NOAC prescriptions rose from 1828 in 2016 to 13,998 in 2021 but dropped to 13,166 in 2022. The percentage of annual prescriptions for NOACs among stroke patients has increased from 0.05% in 2016 to 0.37% in 2022. Total drug cost increased from ¥704541.18 in 2016 to ¥4128648.44 in 2021, then decreased to ¥1680109.14 in 2022. Prescriptions were divided into 48,321 appropriate and 11,262 inappropriate dosing groups, showing significant differences in medications, age, year, city type, hospital level, source, insurance type, and department visited (all p < 0.001). The median drug cost for inappropriate dosing was higher than for appropriate dosing (¥55.20 VS ¥83.80). The top comorbidities in ischemic stroke patients were atrial fibrillation (35.30%), hypertension (32.75%), and coronary heart disease (16.48%). Conclusion: The application of NOACs in the Chinese population is increasing. Our findings highlight the frequent deviation from labeled dosing of NOACs in clinical practice. Continued efforts are necessary to promote the appropriate use of NOACs according to the standard dosage in the drug insert.

Correction: Wang et al. Microarray Profile of Long Noncoding RNA and Messenger RNA Expression in a Model of Alzheimer's Disease. Life 2020, 10, 64.

We have updated the email addresses of Li Zeng and Hailun Jiang as the two authors' previous email addresses are no longer in use [...].

COVID-19, vaccination and migraine: Causal association or epiphenomenon?

BACKGROUND: Diverse studies have revealed discrepant evidence concerning the causal association between Corona Virus Disease 2019 (COVID-19) and COVID-19 vaccination in relation to migraines. Investigating the correlation between the former two factors and migraines can facilitate policymakers in the precise formulation of comprehensive post-pandemic interventions while urging the populace to adopt a judicious perspective on COVID-19 vaccination. METHODS: We undertook a Mendelian randomization (MR) study. The primary assessment of the causal relationship between the three different COVID-19 exposures and migraine was conducted using the standard inverse variance weighted (IVW) approach. In the supplementary analysis, we also employed two methodologies: the weighted median estimator (WME) and the MR-Egger regression. Ultimately, the reliability and stability of the outcomes were assessed via Cochran's Q test, the leave-one-out method, the MR-Egger intercept test, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. RESULTS: The results indicate an absence of correlation between genetically predicted COVID-19 (①Very severe respiratory confirmed COVID-19: odds ratio [OR], 1.0000881; 95%CI, 0.999748-1.000428; p = 0.6118; ②Hospitalized COVID-19: OR, 1.000024; 95%CI, 0.9994893-1.000559; p = 0.931;③SARS-CoV-2 infection: OR, 1.000358; 95%CI, 0.999023-1.001695; p = 0.5993) and the risk of migraine. Furthermore, the MR-Egger regression and WME also yielded no evidence of COVID-19 elevating the risk of migraine occurrence. Sensitivity analysis affirmed the robustness and consistency of all outcomes. CONCLUSIONS: The results of this study do not offer genetic evidence to substantiate a causal relationship between COVID-19 and migraines. Thus, the deduction drawn from COVID-19 genetic data is that COVID-19 vaccination is unlikely to exert an impact on the occurrence of migraines, though this conclusion warrants further investigation.

The mechanistic effects of acupuncture in rodent neurodegenerative disease models: a literature review.

Neurodegenerative diseases refer to a battery of medical conditions that affect the survival and function of neurons in the brain, which are mainly presented with progressive loss of cognitive and/or motor function. Acupuncture showed benign effects in improving neurological deficits, especially on movement and cognitive function impairment. Here, we reviewed the therapeutic mechanisms of acupuncture at the neural circuit level in movement and cognition disorders, summarizing the influence of acupuncture in the dopaminergic system, glutamatergic system, γ-amino butyric acid-ergic (GABAergic) system, serotonergic system, cholinergic system, and glial cells at the circuit and synaptic levels. These findings can provide targets for clinical treatment and perspectives for further studies.

Acupuncture for insomnia symptoms in hypertensive patients: a systematic review and meta-analysis.

Purpose: In the realm of pain management, traditional Chinese medicine, specifically acupuncture, has garnered increasing attention. This meta-analysis pioneers the evaluation of acupuncture's effectiveness in treating insomnia among hypertensive patients. Methods: We conducted a comprehensive search across several databases-PubMed, Web of Science, Cochrane Library, WANFANG, China National Knowledge Infrastructure (CNKI), Sinomed, and the Chinese Journal of Science and Technology (VIP). Additionally, forward and backward articles of studies published from the inception of these databases until 10 September 2023, were reviewed. This systematic review and meta-analysis included all randomized controlled trials (RCTs) focusing on acupuncture for insomnia in hypertensive patients, without imposing language or date restrictions. We rigorously assessed all outcome measures reported in these trials. The evidence was synthesized by calculating the difference between mean differences (MD) in symptom change. The quality of the evidence was determined using the Cochrane Risk of Bias tool. This study is registered with PROSPERO under number CRD42023461760. Results: Our analysis included 16 RCTs, comprising 1,309 patients. The findings revealed that acupuncture was significantly more effective than the control group in reducing insomnia symptoms, as indicated by a greater decrease in the PSQI score (MD = -3.1, 95% CI [-3.77 to -2.62], p < 0.00001). Additionally, improvements in both systolic and diastolic blood pressure were more pronounced in the acupuncture group compared to the control group (SBP: MD = -10.31, 95% CI [-16.98 to -3.64], p = 0.002; DBP: MD = -5.71, 95% CI [-8.19 to -3.23], p < 0.00001). These results suggest that acupuncture not only improves sleep quality but also lowers blood pressure in patients suffering from hypertension and insomnia. Further research is warranted to elucidate optimal acupuncture points and the duration of treatment for maximized therapeutic effect.Systematic review registration:https://www.crd.york.ac.uk/prospero, CRD42023461760.

Assessment of corticospinal tract remodeling based on diffusion tensor imaging in the treatment of motor dysfunction after ischemic stroke by acupuncture: A meta-analysis.

BACKGROUND: To investigate the efficacy of acupuncture in improving motor dysfunction after ischemic stroke (IS) and to investigate the effect of acupuncture on corticospinal tract (CST) remodeling using diffusion tensor imaging. METHODS: Published literature on the effect of acupuncture on CST remodeling after IS using diffusion tensor imaging in the form of randomized controlled trials (RCTs) were systematically retrieved and screened from Cochrane Library, Web of Science, PubMed, Embase, CNKI, CBM, VIP, and Wanfang databases from inception to December 2022. The methodological quality of the included studies was critically and independently evaluated by 2 reviewers using the Cochrane Risk of Bias Assessment Tool for RCTs. The correlated data were extracted using the pre-designed form, and all analyses were performed using Reviewer Manager version 5.4. RESULTS: Eleven eligible RCTs involving 459 patients were eventually included. The combined evidence results showed that the acupuncture group significantly improved patients' National Institute of Health stroke scale, Fugl-Meyer Assessment Scale, and Barthel index compared with conventional medical treatment. The acupuncture group significantly promoted remodeling of the CST, as reflected by an increase in fractional anisotropy (FA) throughout the CST [MD = 0.04, 95% CI (0.02, 0.07), P = .001], and in addition, subgroup analysis showed that the acupuncture group significantly improved FA in the infarct area compared with conventional medical treatment at around 4 weeks [MD = 0.04, 95% CI (0.02, 0.06), P = .0002] and FA of the affected cerebral peduncle [MD = 0.03, 95% CI (0.00, 0.07), P = .02]. Also, compared with conventional medical treatment, the acupuncture group significantly increased average diffusion coefficient of the affected cerebral peduncle [MD = -0.21, 95% CI (-0.28, -0.13), P < .00001]. CONCLUSION: The results of the meta-analysis suggest that acupuncture therapy can improve the clinical manifestations of motor dysfunction in patients after IS and advance a possibly beneficial effect on CST remodeling. However, due to the number and quality of eligible studies, these findings need to be further validated in more standardized, rigorous, high-quality clinical trials.

Prospective observational studies on nutrition intake and the incidence of cognitive impairment in middle-aged and older adults: A protocol for systematic review and meta-analysis.

INTRODUCTION: According to several studies, a specific dietary pattern can reduce the risk of dementia and cognitive impairment. However, the robustness of these results has not been tested. The study intends to investigate the association between nutrition intake and cognitive impairment in middle-aged and older adults (≥45-years) and provide reliable, evidence-based references for healthcare decision-makers, researchers, and policymakers. REVIEW QUESTION: Are the dietary characteristics of community-dwelling adults (≥45-years) associated with the occurrence of cognitive impairment? OBJECTIVES: The primary objective of this protocol is to synthesize the longitudinal observational evidence on the relationship between nutrition intake patterns and the incidence of cognitive impairment in middle-aged and older adults (≥45-years), and to provide detailed dietary recommendations for the prevention of cognitive impairment in this population. METHODS AND ANALYSIS: Cohort studies conducted among adults (≥45-years) will be included. The following electronic databases will be searched for relevant records published by July 2023, with a restriction on language to English: Pubmed, Medline, Embase, Web of science, Cochrane Library. The studies will be selected, the data will be extracted, and the bias risk will be assessed by two independent investigators. The Meta-analysis of Observational Studies in Epidemiology guidelines will be followed to summarize observational studies, and the protocol will adhere to the recommendations from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Endnote X9 will be used to manage data screening. We will use Review Manager 5.4 and Stata 16.0 to conduct data analysis, and a random-effects model will be applied to pool clinically homogenous studies. The results will be presented based on the form of nutrition intake. For assessing publication bias, Egger's test and visual inspection of funnel plots will be utilized. ETHICS AND DISSEMINATION: As this study does not involve primary data, ethical approval is not required. The final report will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: A registration number of DOI 10.17605/OSF.IO/NAKC3 was assigned to it on October 15, 2022 on Prospero.

Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease.

AIMS: Alzheimer's disease (AD) is a neurodegenerative disease with challenging early diagnosis and effective treatments due to its complex pathogenesis. AD patients are often diagnosed after the appearance of the typical symptoms, thereby delaying the best opportunity for effective measures. Biomarkers could be the key to resolving the challenge. This review aims to provide an overview of application and potential value of AD biomarkers in fluids, including cerebrospinal fluid, blood, and saliva, in diagnosis and treatment. METHODS: A comprehensive search of the relevant literature was conducted to summarize potential biomarkers for AD in fluids. The paper further explored the biomarkers' utility in disease diagnosis and drug target development. RESULTS: Research on biomarkers mainly focused on amyloid-ß (Aß) plaques, Tau protein abnormal phosphorylation, axon damage, synaptic dysfunction, inflammation, and related hypotheses associated with AD mechanisms. Aß42 , total Tau (t-Tau), and phosphorylated Tau (p-Tau), have been endorsed for their diagnostic and predictive capability. However, other biomarkers remain controversial. Drugs targeting Aß have shown some efficacy and those that target BACE1 and Tau are still undergoing development. CONCLUSION: Fluid biomarkers hold considerable potential in the diagnosis and drug development of AD. However, improvements in sensitivity and specificity, and approaches for managing sample impurities, need to be addressed for better diagnosis.

Corrigendum: Tilianin extracted from Dracocephalum moldavica L. induces intrinsic apoptosis and drives inflammatory microenvironment response on pharyngeal squamous carcinoma cells via regulating TLR4 signaling pathways.

[This corrects the article DOI: 10.3389/fphar.2020.00205.].

Application of diffusion tensor imaging in the diagnosis of post-stroke aphasia: a meta-analysis and systematic review.

Introduction: Diffusion Tensor Imaging (DTI) indicators of different white matter (WM) fibers and brain region lesions for post-stroke aphasia (PSA) are inconsistent in existing studies. Our study examines the consistency and differences between PSA tests performed with DTI. In addition, obtaining consistent and independent conclusions between studies was made possible by utilizing DTI in PSA assessment. Methods: In order to gather relevant studies using DTI for diagnosing PSA, we searched the Web of Science, PubMed, Embase, and CNKI databases. Based on the screening and evaluation of the included studies, the meta-analysis was used to conduct a quantitative analysis. Narrative descriptions were provided for studies that met the inclusion criteria but lacked data. Results: First, we reported on the left hemisphere. The meta-analysis showed that fractional anisotropy (FA) of the arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF), inferior frontal-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF) were decreased in the PSA group in comparison with the healthy controls (p < 0.00001). However, in the comparison of axial diffusivity (AD), there was no statistically significant difference in white matter fiber tracts in the dual-stream language model of the PSA group. Elevated radial diffusivity (RD) was seen only in the IFOF and ILF (PIFOF = 0.01; PILF = 0.05). In the classic Broca's area, the FA of the PSA group was decreased (p < 0.00001) while the apparent diffusion coefficient was elevated (p = 0.03). Secondly, we evaluated the white matter fiber tracts in the dual-stream language model of the right hemisphere. The FA of the PSA group was decreased only in the IFOF (p = 0.001). AD was elevated in the AF and UF (PAF < 0.00001; PUF = 0.009). RD was elevated in the AF and UF (PAF = 0.01; PUF = 0.003). The other fiber tracts did not undergo similar alterations. Conclusion: In conclusion, DTI is vital for diagnosing PSA because it detects WM changes effectively, but it still has some limitations. Due to a lack of relevant language scales and clinical manifestations, diagnosing and differentiating PSA independently remain challenging. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=365897.

Erratum: Implications of miR-148a-3p/p35/PTEN signaling in tau hyperphosphorylation and autoregulatory feedforward of Akt/CREB in Alzheimer's disease.

[This corrects the article DOI: 10.1016/j.omtn.2021.11.019.].

Acupuncture for the treatment of thalamencephalic and mesencephalic injury secondary to electrical trauma: A case report.

In a case of thalamencephalic and mesencephalic injury secondary to electrical trauma, a 29-year-old patient has been receiving manual acupuncture for 17 months in National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion. As a result of treatment, the patient's self-care ability and quality of life have greatly improved. In order to fully understand how acupuncture can benefit neurological sequelae resulting from electrical trauma, further research is needed. Additionally, there should be consideration given to the promotion of acupuncture therapy in the neurological sequelae of electric shock.