Exploring the Light-Emitting Agents in Renilla Luciferases by an Effective QM/MM Approach.

Bioluminescence is a fascinating natural phenomenon, wherein organisms produce light through specific biochemical reactions. Among these organisms, Renilla luciferase (RLuc) derived from the sea pansy Renilla reniformis is notable for its blue light emission and has potential applications in bioluminescent tagging. Our study focuses on RLuc8, a variant of RLuc with eight amino acid substitutions. Recent studies have shown that the luminescent emitter coelenteramide can adopt multiple protonation states, which may be influenced by nearby residues at the enzyme's active site, demonstrating a complex interplay between protein structure and bioluminescence. Herein, using the quantum mechanical consistent force field method and the semimacroscopic protein dipole-Langevin dipole method with linear response approximation, we show that the phenolate state of coelenteramide in RLuc8 is the primary light-emitting species in agreement with experimental results. Our calculations also suggest that the proton transfer (PT) from neutral coelenteramide to Asp162 plays a crucial role in the bioluminescence process. Additionally, we reproduced the observed emission maximum for the amide anion in RLuc8-D120A and the pyrazine anion in the presence of a Na+ counterion in RLuc8-D162A, suggesting that these are the primary emitters. Furthermore, our calculations on the neutral emitter in the engineered AncFT-D160A enzyme, structurally akin to RLuc8-D162A but with a considerably blue-shifted emission peak, aligned with the observed data, possibly explaining the variance in emission peaks. Overall, this study demonstrates an effective approach to investigate chromophores' bimolecular states while incorporating the PT process in emission spectra calculations, contributing valuable insights for future studies of PT in photoproteins.

Revisiting the predictive role of truncal-type occlusion sign for acute large vessel stroke treated by endovascular thrombectomy: A scoping review.

Background and purpose The truncal type occlusion (TTO) sign observed during endovascular thrombectomy (EVT) is thought to predict the etiology and prognosis of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, the interpretation of the present results and the clinical utility of this sign needs further investigation. This scoping meta-review aimed to assess the predictive value of the TTO sign, thus identifying methodological limitations in current study designs. Methods Studies published up to January 2023 were identified by systematically searching PubMed, Embase, and Web of Science. A meta-analysis was performed to quantitatively synthesize the evidence on the predictive value of the TTO sign. An 8-point scale was introduced to narratively summarize the current evidence level and methodological quality of included studies. Results We included 10 studies in this review. For the prediction of intracranial atherosclerotic stenosis, the sensitivity, specificity, PLR and NLR of the TTO sign were 0.73, 0.87, 5.5 and 0.31, respectively (all p<0.05). For recanalization failure after primary thrombectomy, the sensitivity, specificity, PLR and NLR were 0.44, 0.91, 4.9 and 0.61, respectively (all p<0.05). The strength of evidence was low due to the methodological limitations and lack of adjustment for potential confounders. Conclusion The predictive values of the TTO sign for the etiology of LVO-AIS was considerable but seemed limited for current interpretation. Several confounders could influence the determination and predictive value of the TTO sign, requiring methodological adjustments in future research. Endovascular practitioners encountering this sign during thrombectomy should draw specific attention to stroke etiology, thus promoting timely adjustment of intra- and postprocedural strategies.

Prognostic value of the neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis.

BACKGROUND: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and poor prognostics in acute ischemic stroke (AIS) patients who receive intravenous thrombolysis (IVT) remains controversial. The purpose of this systematic review and meta-analysis was to evaluate the association between the NLR and poor prognosis after IVT. Furthermore, we aimed to determine whether the NLR at admission or post-IVT plays a role in AIS patients who received IVT. METHODS: The PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases were searched for relevant articles until October 7, 2020. Cohort and case-control studies were included if they were related to the NLR in AIS patients treated with IVT. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were pooled to estimate the relationship between NLR and poor prognosis after IVT. A random effects model was used to calculate the pooled data. RESULTS: Twelve studies, including 3641 patients, met the predefined inclusion criteria. Higher NLRs were associated with an increased risk of hemorrhagic transformation (HT) (OR = 1.33, 95 % CI = 1.14-1.56, P < 0.001) and a poor 3-month functional outcome (OR = 1.64, 95 % CI = 1.38-1.94, P < 0.001) in AIS patients who received IVT. Subgroup analysis suggested that the NLR at admission rather than post-IVT was associated with a higher risk of HT (OR = 1.33, 95 % CI = 1.01-1.75, P = 0.039). There was no statistically significant difference between higher NLRs and 3-month mortality (OR = 1.14, 95 % CI = 0.97-1.35, P = 0.120). CONCLUSIONS: A high NLR can predict HT and poor 3-month functional outcomes in AIS patients who receive IVT. The NLR at admission rather than the post-IVT NLR was an independent risk factor for an increased risk of HT after IVT.

Comparison of the Diagnostic Performances of Ultrasound, High-Resolution Magnetic Resonance Imaging, and Positron Emission Tomography/Computed Tomography in a Rabbit Carotid Vulnerable Plaque Atherosclerosis Model.

OBJECTIVES: Our study aimed to evaluate the diagnostic performances of 3 routine examination methods for cerebrovascular disease in a rabbit carotid artery atherosclerosis model. METHODS: A total of 12 New Zealand rabbits were included: 4 in a control group and 8 in an experimental group. A clinically relevant atherosclerosis rabbit model was induced by left common carotid artery ligation and a 12-week high-fat diet. Atherosclerosis was further confirmed by a histopathologic analysis. Then carotid ultrasound (US) imaging, high-resolution magnetic resonance imaging (HRMRI), and positron emission tomography (PET)/computed tomography (CT) were performed on this model to evaluate the diagnostic performances. RESULTS: Carotid US showed plaque formation in the left common carotid artery and little plaque in the right common carotid artery in the experimental group. In addition, HRMRI showed stenosis formation in the left common carotid artery in the experimental group. At the horizontal level, plaques were found in the left common carotid artery, and no plaques were found in the right common carotid artery in the experimental group. Also, PET/CT showed local hypermetabolism and vulnerable plaques in the left common carotid artery of the experimental group, whereas no hypermetabolism was found in the right common carotid artery of the experimental group. Moreover, the soft plaques detected by carotid US were different from the vulnerable plaques detected by PET/CT. The unstable plaques on HRMRI were the same as the hypermetabolic vulnerable plaques on PET/CT. CONCLUSIONS: High-resolution MRI is recommended for the evaluation of neck and intracranial vascular stenosis and plaque properties in patients with stroke.

Knockdown of microRNA-17-5p Enhances the Neuroprotective Effect of Act A/Smads Signal Loop After Ischemic Injury.

Cerebral ischemic injury is a leading cause of human mortality and disability, seriously threatening human health in the world. Activin A (Act A), as a well-known neuroprotective factor, could alleviate ischemic brain injury mainly through Act A/Smads signaling. In our previous study, a noncanonical Act A/Smads signal loop with self-amplifying property was found, which strengthened the neuroprotective effect of Act A. However, this neuroprotective effect was limited due to the self-limiting behavior mediated by Smad anchor for receptor activation (SARA) protein. It was reported that microRNA-17-5p (miR-17-5p) could suppress the expression of SARA in esophageal squamous cell carcinoma. Thus we proposed that knockdown of miR-17-5p could strengthen the neuroprotective effect of Act A/Smads signal loop through SARA. To testify this hypothesis, oxygen-glucose deficiency (OGD) was introduced to highly differentiated rattus pheochromocytoma (PC12) cells. After the transfection of miR-17-5p mimic or inhibitor, the activity of Act A signal loop was quantified by the expression of phosphorylated Smad3. The results showed that suppression of miR-17-5p up-regulated the expression of SARA protein, which prolonged and strengthened the activity of Act A signaling through increased phosphorylation of downstream Smad3 and accumulation of Act A ligand. Further luciferase assay confirmed that SARA was a direct target gene of miR-17-5p. These practical discoveries will bring new insight on the endogenous neuroprotective effects of Act A signal loop by interfering a novel target: miR-17-5p.

Suppressed microRNA-96 inhibits iNOS expression and dopaminergic neuron apoptosis through inactivating the MAPK signaling pathway by targeting CACNG5 in mice with Parkinson's disease.

BACKGROUND: There have been a number of reports implicating the association of microRNAs (miRs) and the MAPK signaling pathway with the dopaminergic neuron, which is involved in the development of Parkinson's disease (PD). The present study was conducted with aims of exploring the role of miR-96 in the activation of iNOS and apoptosis of dopaminergic neuron through the MAPK signaling pathway in mice with PD. METHODS: The miR and the differentially expressed gene in PD were screened out and the relationship between them was verified. A mouse model of PD induced by MPTP and was then constructed and treated with miR-96 mimic/inhibitor and CACNG5 overexpression plasmid to extract nigral dopaminergic neuron for the purpose of detecting the effect of miR-96 on PD. The TH and iNOS positive neuronal cells, the apoptotic neuronal cells by TUNEL staining, and expression of miR-96, CACNG5, iNOS, p38MAPK, p-p38MAPK, c-Fos, Bax, and Bcl-2 in substantia nigra dopaminergic neuronal tissues were evaluated. RESULTS: The results obtained from the aforementioned procedure were then verified by cell culture of the SH-SY5Y cells, followed by treatment with miR-96 mimic/inhibitor, CACNG5 overexpression plasmid and the inhibitor of the MAPK signaling pathway. CACNG5 was confirmed as a target gene of miR-96. The inhibition of miR-96 resulted in a substantial increase in nigral cells, TH positive cells and expression of CACNG5 and Bcl-2 in nigral dopaminergic neuronal tissues, and a decrease in iNOS positive cells, apoptotic neuronal cells, and expression of iNOS, p38MAPK, p-p38MAPK, c-Fos, and Bax. CONCLUSION: The above results implicated that the downregulation of miR-96 inhibits the activation of iNOS and apoptosis of dopaminergic neuron through the blockade of the MAPK signaling pathway by promoting CACNG5 in mice with PD.

Association between SORL1 polymorphisms and the risk of Alzheimer's disease.

A meta-analysis was performed to identify empirical data assessing the effects of a single nucleotide polymorphisms of sortilin related receptor on Alzheimer's disease based on 14 studies involving 37941 cases and 49727 control studies. Analysis showed, (i) Increased risk between the single nucleotidepolymorphisms (rs641120, rs1010159) and Alzheimer's disease susceptibility inAsian populations, (ii) Single nucleotide polymorphism rs689021 was associatedwith decreased risk in Caucasians, and (iii) Single nucleotide polymorphismrs641120 was detected as a decreased risk in both populations. Given thesedata, crucial evidence is provided to demonstrate that a significantrelationship exists between SORL1 polymorphisms and susceptibility to Alzheimer's disease.

Efficacy and Prognostic Value of Partial Sensory Rhizotomy and Microvascular Decompression for Primary Trigeminal Neuralgia: A Comparative Study.

BACKGROUND This study aimed to compare the efficacy and prognostic value of partial sensory rhizotomy (PSR) and microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). MATERIAL AND METHODS From June 2010 to June 2012, 117 patients with PTN were recruited for the study, of which 52 cases were treated with MVD (the MVD group) and 65 cases were treated with PSR (the PSR group). Visual Analog Scoring (VAS) was performed at 1 and 2 weeks, and at 1, 3, and 6 month after surgery. The overall response rate (ORR) was determined 1 month after surgery. Barrow Neurological Institute score was adopted to value the reoccurrence at 6, 12, 24, and 36 months after surgery. A 3-year follow-up was conducted and the complications were recorded. RESULTS The ORR 2 weeks after surgery in the MVD and PSR groups was 98.08% and 84.62%, respectively. One and 2 weeks after surgery, the VAS was lower in the MVD group than in the PSR group, but there was no significant difference in VAS between the 2 groups at 1, 3, and 6 months after surgery. Three years after surgery, the recurrence rate was significantly lower in the MVD group than in the PSR group. The recurrence-free survival time was longer in the MVD group than in the PSR group. The occurrence rates of herpes and total postoperative complications were significantly higher in the PSR group than in the MVD group. CONCLUSIONS Compared with PSR, MVD is more suitable for PTN treatment, with less disturbance, lower recurrence rate, and better efficacy.

Activin A/Smads signaling pathway negatively regulates Oxygen Glucose Deprivation-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Activin A (Act A), a member of the transforming growth factor-beta (TGF-ß), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells. In addition, we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy. The activation of JNK and p38 MAPK pathways in OGD-treated PC12 cells was suppressed by exogenous Act A and enhanced by ActRIIA-Ab. Together, our results suggest that Act A/Smads signaling pathway negatively regulates OGD-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop.

Activin A (Act A), a member of transforming growth factor-ß superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling.

The ABCD2 score may underestimate the short-term risk of stroke in Chinese population: A meta-analysis.

OBJECTIVES: The ABCD2 score has been commonly used to triage patients with transient ischemic attack (TIA) who are at high risk for imminent stroke. However, its accuracy in predicting short-term stroke risk among TIA patients in China remains unclear. METHODS: All eligible studies published up to May 2014 were identified by searching Medline, PubMed, Embase, the China Knowledge Resource Integrated Database (CNKI) and the China Biological Medicine Database (CBM-disc), as well as unpublished articles manually scanned. The strength of the associations between treatments and outcomes was estimated by incorporated risk ratios (RRs) and 95% confidence intervals (CIs) using the Mantel-Haenszel statistical method. RESULTS: Eight and 32 studies, which validated the value for predicting the risk of stroke 2 and 7 days after TIA respectively, were included. We calculated the RRs and CIs for 2- and 7-day prediction for stroke (low: RR=0.43, 95% CI=0.17-1.10, I2=0%; moderate: RR=0.42, 95% CI=0.26-0.67, I2=0%; high: RR=0.32, 95% CI=0.21-0.48, I2=0%; and low: RR=0.29, 95% CI=0.20-0.44, I2=0%; moderate: RR=0.27, 95% CI=0.23-0.33, I2=0%; high: RR=0.22, 95% CI=0.18-0.27, I2=1%). CONCLUSIONS: This meta-analysis indicated that the ABCD2 score may highly under-predict the short-term occurrence of stroke after TIA for the Chinese population compared with the original model derived from Caucasian populations, which may lead to neglect of the short-term risk for stroke in the clinical practice.

Anti-fatigue effects of polysaccharides extracted from Portulaca oleracea L. in mice.

Portulaca oleracea L. has been used as a food and medicinal plant for thousands of years in China. Polysaccharides extracted from P. oleracea L. (POP) are its main bioactive compound and have multiple pharmacological activities. However, anti-fatigue effects of POP have not yet been tested. This study was designed to investigate the anti-fatigue effects of POP in mice using the rotarod and forced swimming tests. The mice were randomly divided into four groups, namely normal control group, low-dose POP supplementation group, medium-dose POP supplementation group and high-dose POP supplementation group. The normal control group received distilled water and the supplementation groups received different doses of POP (75, 150 and 300 mg/kg, respectively). The POP or distilled water was administered orally and daily for 30 day. After 30 days, the rotarod and forced swimming tests were performed and then several biochemical parameters related to fatigue were determined. The data showed that POP prolonged the riding times and exhaustive swimming times of mice, decreasing blood lactic acid and serum urea nitrogen levels, as well as increasing the liver and muscle glycogen contents. These results indicated that POP had the anti-fatigue effects.

Enhancement of therapeutic potential of mesenchymal stem cell by IGF-1 delivery in PLGA microspheres for tissue regeneration.

The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.

Effects of SARA on oxygen-glucose deprivation in PC12 cell line.

Ischemic stroke is a major composition of cerebrovascular disease, seriously threatening to human health in the world. Activin A (ActA), belonging to transforming growth factor-beta (TGF-ß) super family, plays an important role in the hypoxic-ischemic brain injury through ActA/Smads pathway. While as an essential phosphorylation assistor in TGF-ß signaling, the functions and mechanisms of smad anchor for receptor activation (SARA) in ischemic brain injury remain poorly understood. To solve this problem and explore the pathological processes of ischemic stroke, we used an Oxygen-Glucose deprivation (OGD) model in nerve growth factor-induced differentiated rattus PC12 pheochromocytoma cells and down regulated the expressions of SARA by RNA interference technology. Our results showed that the repression of SARA before OGD exposure reduced the expressions of Smad2, 3, 4 mRNA and the phosphorylation rate of Smad2 protein, but it did not affect the mRNA expressions of Smad7. After OGD treatment, ActA/Smads pathway was activated and the expression of SARA in the SARA pre-repression group was significantly up-regulated. The pre-repression of SARA increased the sensitivities of nerve-like cells to OGD damage. Moreover, the mRNA expression of Smad7 which was supposed to participate in the negative feedback of ActA/Smads pathway was also elevated due to OGD injury. Taken together, these results suggest a positive role of SARA in assisting the phosphorylation of Smad2 and maintaining the neuron protective effect of ActA/Smads pathway.

Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells.

Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

Neuroprotective Effects of Activin A against Cerebral Ischemia/Reperfusion Injury in Mice by Enhancing Nrf2 Expression to Attenuate Neuronal Ferroptosis.

Activin A (Act A) is a member of the transforming growth factor-ß (TGF-ß) superfamily and can protect against ischemic cerebral injury. Ferroptosis, a newly discovered type of programmed cell death, contributes to the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). However, little is known on whether Act A can modulate neuronal ferroptosis to protect against CIRI in a mouse model of middle cerebral artery occlusion (MCAO) and an HT22 cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The results indicated that Act A treatment relieved CIRI by improving neurological deficits and reducing the infarct volume in mice. MCAO stimulated iron accumulation and malondialdehyde formation and upregulated ACSL4 expression but downregulated GPX4 expression, a hallmark of ferroptosis in the brain of mice. Treatment with Act A significantly mitigated MCAO-triggered ferroptosis in the brain of mice. Furthermore, Act A treatment enhanced the MCAO-upregulated nuclear factor erythroid-2-related factor 2 (Nrf2) expression in the brains of mice. Similar results were observed in HT22 cells following OGD/R and pretreatment with Act A. The neuronal protective effect of Act A in HT22 cells was attenuated by treatment with ML385, an Nrf2 inhibitor. To conclude, Act A attenuated CIRI by enhancing Nrf2 expression and inhibiting neuronal ferroptosis.

Multi-Target Neuroprotection of Thiazolidinediones on Alzheimer's Disease via Neuroinflammation and Ferroptosis.

Alzheimer's disease (AD) is the main cause of dementia in older age. The prevalence of AD is growing worldwide, causing a tremendous burden to societies and families. Due to the complexity of its pathogenesis, the current treatment of AD is not satisfactory, and drugs acting on a single target may not prevent AD progression. This review summarizes the multi-target pharmacological effects of thiazolidinediones (TZDs) on AD. TZDs act as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and long-chain acyl-CoA synthetase family member 4 (ACSL4) inhibitors. TZDs ameliorated neuroinflammation and ferroptosis in preclinical models of AD. Here, we discussed recent findings from clinical trials of pioglitazone in the treatment of AD, ischemic stroke, and atherosclerosis. We also dissected the major limitations in the clinical application of pioglitazone and explained the potential benefit of pioglitazone in AD. We recommend the use of pioglitazone to prevent cognitive decline and lower AD risk in a specific group of patients.

Comparative Efficacy and Acceptability of Cholinesterase Inhibitors and Memantine Based on Dosage in Patients with Vascular Cognitive Impairment: A Network Meta-analysis.

BACKGROUND: Considering the lack of direct comparison between cholinesterase inhibitors and memantine in patients with vascular cognitive impairment (VCI), determining how to choose the best treatment plan remains inconclusive. Hence, we conducted the network meta-analysis to compare the efficacy and acceptability of these drugs. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for double-blind randomized controlled trials (RCTs) for the treatment of VCI, which involved donepezil, galantamine, rivastigmine, and memantine, from database inception to January 1, 2020. Then, a network meta-analysis based on the frequency method was conducted. RESULTS: Eleven RCTs were included. Compared with the placebo, in terms of efficacy, donepezil 5 mg (standardized mean difference = -1.11, 95% confidence interval = -1.88 to -0.34), donepezil 10 mg (-1.44, -2.31 to -0.56), galantamine 24 mg (-1.99, -3.03 to -0.95), and memantine 20 mg (-1.89, -2.93 to -0.86) were more effective for the cognition of ADAS-cog, and donepezil 5 mg (0.46, 0.12 to 0.81), donepezil 10 mg (0.76, 0.34 to 1.17), and rivastigmine 12mg (0.60, 0.10 to 1.10) exhibited superior benefits for the cognition of MMSE. Donepezil 10 mg (-0.25, -0.44 to -0.06; -1.47, -2.79 to -0.15) exhibited improvements for CDR-SB and EXIT25, respectively. In terms of acceptability, memantine was found to be the best. CONCLUSION: Donepezil 5 mg, donepezil 10 mg, galantamine 24 mg, memantine 20 mg, and rivastigmine 12 mg exerted beneficial effects on cognition, and donepezil 10mg provided beneficial effects for executive function and global status. Based on the network meta-analysis, donepezil 10 mg might be the best choice, considering the benefits on cognition function, executive function and global status, but doserelated adverse reactions need to be noted. In the meantime, memantine is a better comprehensive choice in terms of efficacy and safety.

Neurovascular compression syndrome:Trigeminal neuralgia, hemifacial spasm, vestibular paroxysmia, glossopharyngeal neuralgia, four case reports and review of literature.

Neurovascular compression syndrome is caused by vessels touching a cranial nerve, resulting in clinical manifestations of abnormal sensory or motor symptoms. The most common manifestations are trigeminal neuralgia and hemifacial spasm. However, neurovascular compression of the vestibular nerve or glossopharyngeal nerve are rare. In this article, we describe four typical cases of neurovascular compression syndrome. In addition, we analyze the main features of the etiology, neuroimaging, and treatment of this disease.