Transplantation of Wnt5a-modified Bone Marrow Mesenchymal Stem Cells Promotes Recovery After Spinal Cord Injury via the PI3K/AKT Pathway.

Spinal cord injury (SCI) is a severe neurological condition that can lead to paralysis or even death. This study explored the potential benefits of bone marrow mesenchymal stem cell (BMSC) transplantation for repairing SCI. BMSCs also differentiate into astrocytes within damaged spinal cord tissues hindering the cell transplantation efficacy, therefore it is crucial to enhance their neuronal differentiation rate to facilitate spinal cord repair. Wnt5a, an upstream protein in the non-classical Wnt signaling pathway, has been implicated in stem cell migration, differentiation, and neurite formation but its role in the neuronal differentiation of BMSCs remains unclear. Thus, this study investigated the role and underlying mechanisms of Wnt5a in promoting neuronal differentiation of BMSCs both in vivo and in vitro. Wnt5a enhanced neuronal differentiation of BMSCs in vitro while reducing astrocyte differentiation. Additionally, high-throughput RNA sequencing revealed a correlation between Wnt5a and phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT) signaling, which was confirmed by the use of the PI3K inhibitor LY294002 to reverse the effects of Wnt5a on BMSC neuronal differentiation. Furthermore, transplantation of Wnt5a-modified BMSCs into SCI rats effectively improved the histomorphology (Hematoxylin and eosin [H&E], Nissl and Luxol Fast Blue [LFB] staining), motor function scores (Footprint test and Basso-Beattie-Bresnahan [BBB]scores)and promoted neuron production, axonal formation, and remodeling of myelin sheaths (microtubule associated protein-2 [MAP-2], growth-associated protein 43 [GAP43], myelin basic protein [MBP]), while reducing astrocyte production (glial fibrillary acidic protein [GFAP]). Therefore, targeting the Wnt5a/PI3K/AKT pathway could enhance BMSC transplantation for SCI treatment.

The α4 Nicotinic Acetylcholine Receptor Is Necessary for the Initiation of Organophosphate-Induced Neuronal Hyperexcitability.

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.

Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice.

OBJECTIVE: Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism. METHODS: Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot. RESULTS: The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1ß, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae. CONCLUSIONS: Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment.

Noninvasive Brain Stimulation for Motor Dysfunction After Incomplete Spinal Cord Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to examine the effectiveness of noninvasive brain stimulation on motor dysfunction after incomplete spinal cord injury. METHODS: The PubMed, Embase, and Cochrane Library were searched from the inception dates to April 30, 2022. Randomized controlled trials comparing the effects of noninvasive brain stimulation and sham stimulation on motor dysfunction in patients with incomplete spinal cord injury were included. Two reviewers performed the data extraction and assessed study quality using Cochrane Collaboration's Tool. The primary outcomes involved upper limb function, lower limb function, spasticity, and activities of daily living. They were analyzed using meta-analysis method and the results were reported as standardized mean difference with 95% confidence interval. RESULTS: Fourteen studies involving 225 patients were included. Noninvasive brain stimulation reduced spasticity at the end of intervention (standardized mean difference = -0.68, 95% confidence interval = -1.32 to -0.03, P = 0.04) and 1-wk follow-up (standardized mean difference = -0.82, 95% confidence interval = -1.48 to -0.16, P = 0.02), but no beneficial effect at 1-mo follow-up (standardized mean difference = -0.32, 95% confidence interval = -1.06 to 0.42, P = 0.39). In addition, noninvasive brain stimulation also increased lower limb muscle strength at 1-mo follow-up (standardized mean difference = 0.69, 95% confidence interval = 0.11 to 1.28, P = 0.02). Other main outcomes were similar between groups. CONCLUSIONS: Noninvasive brain stimulation can reduce spasticity, and the favorable effect can sustain for 1 wk after intervention. In addition, noninvasive brain stimulation can increase lower limb muscle strength at 1-mo follow-up.

Marginal Zinc Deficiency during Gestation and Lactation in Rats Affects Oligodendrogenesis, Motor Performance, and Behavior in the Offspring.

BACKGROUND: Oligodendrocytes are responsible for myelin production in the central nervous system (CNS). Hypomyelination may slow saltatory nerve signal conduction and affect motor performance and behavior in adults. Gestational marginal zinc deficiency in rats significantly decreases proliferation of neural stem cells (NSCs) in the offspring brain. OBJECTIVES: Given that NSCs are precursors of oligodendrocytes, this study investigated if marginal zinc deficiency during early development in rats affects oligodendrogenesis in the offspring's CNS. METHODS: Rat dams were fed an adequate (25 µg zinc/g diet) (C) or a marginal zinc diet (MZD) (10 µg zinc/g diet), from gestation day zero until postnatal day (P) 20, and subsequently all offspring was fed the control diet until P60. Oligodendrogenesis was evaluated in the offspring at P2, P5, P10, P20, and P60, by measuring parameters of oligodendrocyte progenitor cells (OPCs) proliferation, differentiation, maturation, and of myelination. RESULTS: The expression of 1) proteins that regulate OPC proliferation (Shh, Sox10, Olig2); 2) OPC markers (NG2, PDGFRα); 3) myelin proteins (MBP, MAG, MOG, PLP) were lower in the brain cortex from MZD than C offspring at various stages in development. The amount of myelin after zinc replenishment continued to be low in the MZD young adult at P60. Accordingly, parameters of motor performance and behavior [grip strength, rotarod, elevated T-maze (ETM), and open-field tests] were impaired in the MZD offspring at P60. CONCLUSIONS: Results support the concept that maternal and early postnatal exposure to MZD affects oligodendrogenesis causing long-lasting effects on myelination and on motor performance in the young adult offspring.

Predictors of deep-vein thrombosis for acute stroke at admission to a rehabilitation unit: A retrospective study.

Background: Deep-vein thrombosis (DVT) is a common complication of acute stroke (AS). Only limited studies have discussed DVT in patients with AS at admission to a rehabilitation unit. The purpose of this study is to identify the predictors of DVT in AS patients admitted to a rehabilitation unit in China. Methods: We retrospectively reviewed the medical records of all patients with AS admitted within 14 days of stroke onset between July 2019 and June 2022 at the Department of Rehabilitation Medicine, Xuanwu Hospital, Capital Medical University, China. Ultrasonography was used to diagnose DVT in all patients within 3 days after rehabilitation admission. Univariate and binary logistic regression analyses were performed to determine the risk factors for DVT. Results: Overall, 234 cases were identified and the incidence rate of DVT among AS patients was 13.2% (31/234). The univariate analysis showed that age, drinking, lower limb muscle strength, Brunnstrom Assessment (BRS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Barthel Index (BI) scale, serum albumin (Alb), and D-dimer were statistically significant factors. Age (OR = 1.037, 95% CI = 1.000-1.075, p < 0.05), BBS (OR = 0.952, 95% CI = 0.913-0.993, p < 0.05), and D-dimer (OR = 1.446, 95% CI = 1.130-1.849, p < 0.05) were demonstrated as independent risk factors for DVT. Conclusion: Older age, lower BBS, and higher D-dimer levels at rehabilitation admission were independent risk factors for DVT. Therefore, ultrasonography should be performed for those patients with these three significant factors before implementing rehabilitation therapy.

3D and Inkjet Printing by Colored Mie-Resonant Silicon Nanoparticles Produced by Laser Ablation in Liquid.

Optically resonant silicon nanoparticles have emerged as a prospective platform for the structural coloration of surfaces because of their strong and spectrally selective light scattering. In this work, we developed colorful inks based on polymer mixed with monodisperse Mie-resonant silicon nanoparticles for 3D and inkjet printing. We applied a laser ablation method in a flow cell for the mass production of silicon nanoparticles in water and separated the resulting nanoparticles with different sizes by density-gradient centrifugation. Mixing the colorful nanoparticles with the polymer allows for the printing of 3D objects with various shapes and colors, which are rigid against environmental conditions.

Sirt6 mediates antioxidative functions by increasing Nrf2 abundance.

Oxidative stress caused by excess ROS often leads to cellular macromolecule damage and eventually causes various biological catastrophes. Sirt6, a member of the mammalian homolog family of yeast Sir2 NAD+-dependent histone deacetylases, regulates multiple biological processes. Sirt6 exerts antioxidative functions by enhancing DNA repair and DNA end resection. In our study, we found that Sirt6 expression was induced by H2O2 and paraquat (PQ) in cells. When exposed to PQ, the Sirt6+/- C57BL/6 mice showed more serious liver damage and lower survival rate than the Sirt6+/+ mice. The Nrf2 protein levels and the mRNA levels of its target genes in mouse tissues were decreased by Sirt6 deficiency, and Sirt6 overexpression increased the Nrf2 protein content. Moreover, the endogenous H2O2 levels were increased in the tissues of Sirt6-deficient mice and were decreased in Sirt6 overexpression cells. Then, we found that Nrf2 was degraded faster in the Sirt6-deficient mouse embryonic fibroblasts (MEFs) than in the wild type MEFs and that Sirt6 enhanced the protein accumulation of Nrf2 in the nucleus. Lastly, we found that Sirt6 interacted with Nrf2 in co-IP and GST pull-down assays and that Sirt6 overexpression decreased the binding of Nrf2 to Keap1. Taken together, the results of the present study suggest that Sirt6 exerts antioxidative functions by increasing the Nrf2 protein level via Keap1-mediated regulation.

Impact of cognition on test-retest reliability and concurrent validity of n-back for Chinese stroke patients.

OBJECTIVE: The objective of this study was the measurement of the test-retest reliability of n-back in Chinese stroke patients. METHODS: Seventy-five sub-acute stroke patients performed n-back twice in three days. The test-retest reliability of n-back was analyzed by correlation coefficient. RESULTS: The n-back had excellent test-retest reliability in stroke patients. Pearson or Spearman coefficients ranged from 0.81 to 0.88. The intra-class correlation coefficients ranged from 0.72 to 0.87. The Chinese version of Montreal Cognitive Assessment-Basic (MoCA-BC) score was significantly correlated with the performance of n-back. MoCA-BC and n-back accuracy were significantly related in the Mild Cognitive Impairment (MCI) group (r = 0.60 in 1-back, p = .002; r = 0.43 in 2-back, p = .040). However, MoCA-BC was correlated with reaction time (RT) in the Cognitively Normal (CN) group (r = -0.44 in 1-back, p = .003; r = -0.36 in 2-back, p = .018). The test-retest reliability of CN group was mostly higher than that of MCI group RT: 0.71-0.76 in MCI, 0.80-0.88 in CN; accuracy: 0.80-0.85 in MCI, 0.75-0.86 in CN). The practice effect was observed in the CN group instead of the MCI group. CONCLUSIONS: This study indicated that the test-retest reliability of n-back was high in stroke patients. N-back was correlated with cognition. It was preferable to conduct subgroup analyses according to the level of cognitive assessment of patients with stroke.

Di-2-ethylhexyl phthalate affects zinc metabolism and neurogenesis in the developing rat brain.

We previously observed that developmental marginal zinc deficiency affects neurogenesis. Maternal phthalate exposure could disrupt fetal zinc homeostasis by triggering an acute phase response, causing maternal liver zinc retention that limits zinc availability to the fetus. Thus, we currently investigated whether exposure to di-2-ethylhexyl phthalate (DEHP) during gestation in rats alters fetal brain neurogenesis by impairing zinc homeostasis. Dams consumed an adequate (25 µg zinc/g diet) (C) or a marginal zinc deficient (MZD) (10 µg zinc/g diet) diet, without or with DEHP (300 mg/kg BW) (C + DEHP, MZD + DEHP) from embryonic day (E) 0 to E19. To evaluate neurogenesis we measured parameters of neural progenitor cells (NPC) proliferation and differentiation. Maternal exposure to DEHP and/or zinc deficiency lowered fetal brain cortical tissue (CT) zinc concentrations. Transcription factors involved in NPC proliferation (PAX6, SOX2, EMX1), differentiation (TBR2, TBR1) and mature neurons (NeuN) were lower in MZD, MZD + DEHP and C + DEHP than in C E19 brain CT, being the lowest in the MZD + DEHP group. VGLUT1 levels, a marker of glutamatergic neurons, showed a similar pattern. Levels of a marker of GABAergic neurons, GAD65, did not vary among groups. Phosphorylated ERK1/2 levels were reduced by both MZD and DEHP, and particularly in the MZD + DEHP group. MEHP-treated human neuroblastoma IMR-32 cells and E19 brains from DEHP-treated dams showed that the zinc-regulated phosphatase PP2A can be in part responsible for DEHP-mediated ERK1/2 downregulation and impaired neurogenesis. Overall, gestational exposure to DEHP caused secondary zinc deficiency and impaired neurogenesis. These harmful effects could have long-term consequences on the adult offspring brain structure and function.

Endolymphatic Hydrop Phenotype in Familial Norrie Disease Caused by Large Fragment Deletion of NDP.

Norrie disease (ND; OMIM 310600), a rare X-linked recessive genetic disorder, is characterized by congenital blindness and occasionally, sensorineural hearing loss, and developmental delay. The congenital blindness of ND patients is almost untreatable; thus, hearing is particularly important for them. However, the mechanism of hearing loss of ND patients is unclear, and no good treatment is available except wearing hearing-aid. Therefore, revealing the mechanism of hearing loss in ND patients and exploring effective treatment methods are greatly important. In addition, as a serious monogenic genetic disease, convenient gene identification method is important for ND patients and their family members, as well as prenatal diagnosis and preimplantation genetic diagnosis to block intergenerational transmission of pathogenic genes. In this study, a Norrie family with two male patients was reported. This pedigree was ND caused by large fragment deletion of NDP (norrin cystine knot growth factor NDP) gene. In addition to typical severe ophthalmologic and audiologic defects, the patients showed new pathological features of endolymphatic hydrops (EH), and they also showed acoustic nerves abnormal as described in a very recent report. PCR methods were developed to analyze and diagnose the variation of the family members. This study expands the understanding of the clinical manifestation and pathogenesis of ND and provides a new idea for the treatment of patients in this family and a convenient method for the genetic screen for this ND family.

A Novel missense mutation of COL2A1 gene in a large family with stickler syndrome type I.

Stickler syndrome type I (STL1, MIM 108300) is characterized by ocular, auditory, skeletal and orofacial manifestations. Nonsyndromic ocular STL1 (MIM 609508) characterized by predominantly ocular features is a subgroup of STL1, and it is inherited in an autosomal dominant manner. In this study, a novel variant c.T100>C (p.Cys34Arg) in COL2A1 related to a large nonsyndromic ocular STL1 family was identified through Exome sequencing (ES). Bioinformatics analysis indicated that the variant site was highly conserved and the pathogenic mechanism of this variant may involve in affected structure of chordin-like cysteine-rich (CR) repeats of ColIIA. Minigene assay indicated that this variant did not change alternative splicing of exon2 of COL2A1. Moreover, the nonsyndromic ocular STL1 family with 16 affected members showed phenotype variability and certain male gender trend. None of the family members had hearing loss. Our findings would expand the knowledge of the COL2A1 mutation spectrum, and phenotype variability associated with nonsyndromic ocular STL1. Search for genetic modifiers and related molecular pathways leading to the phenotype variation warrants further studies.

Nrf2 expands the intracellular pool of the chaperone AHSP in a cellular model of ß-thalassemia.

In ß-thalassemia, free α-globin chains are unstable and tend to aggregate or degrade, releasing toxic heme, porphyrins and iron, which produce reactive oxygen species (ROS). α-Hemoglobin-stabilizing protein (AHSP) is a potential modifier of ß-thalassemia due to its ability to escort free α-globin and inhibit the cellular production of ROS. The influence of AHSP on the redox equilibrium raises the question of whether AHSP expression is regulated by components of ROS signaling pathways and/or canonical redox proteins. Here, we report that AHSP expression in K562 cells could be stimulated by NFE2-related factor 2 (Nrf2) and its agonist tert-butylhydroquinone (tBHQ). This tBHQ-induced increase in AHSP expression was also observed in Ter119+ mouse erythroblasts at each individual stage during terminal erythroid differentiation. We further report that the AHSP level was elevated in α-globin-overexpressing K562 cells and staged erythroblasts from ßIVS-2-654 thalassemic mice. tBHQ treatment partially alleviated, whereas Nrf2 or AHSP knockdown exacerbated, α-globin precipitation and ROS production in fetal liver-derived thalassemic erythroid cells. MafG and Nrf2 occupancy at the MARE-1 site downstream of the AHSP transcription start site was detected in K562 cells. Finally, we show that MafG facilitated the activation of the AHSP gene in K562 cells by Nrf2. Our results demonstrate Nrf2-mediated feedback regulation of AHSP in response to excess α-globin, as occurs in ß-thalassemia.

Role of Endoplasmic Reticulum Stress in Otitis Media.

Endoplasmic reticulum (ER) stress occurs in many inflammatory responses. Here, we investigated the role of ER stress and its associated apoptosis in otitis media (OM) to elucidate the mechanisms of OM and the signaling crosstalk between ER stress and other cell damage pathways, including inflammatory cytokines and apoptosis. We examined the expression of inflammatory cytokine- and ER stress-related genes by qRT-PCR, Western blotting, and immunohistochemistry (IHC) in the middle ear of C57BL/6J mice after challenge with peptidoglycan polysaccharide (PGPS), an agent inducing OM. We also evaluated the effect of the suppression of ER stress with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. The study revealed the upregulation of ER stress- and apoptosis-related gene expression after the PGPS treatment, specifically ATF6, CHOP, BIP, caspase-12, and caspase-3. TUDCA treatment of PGPS-treated mice decreased OM; reduced the expression of CHOP, BIP, and caspase 3; and significantly decreased the proinflammatory gene expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These results suggest that PGPS triggers ER stress and downstream proinflammatory gene expression in OM and that inhibition of ER stress alleviates OM. We propose that ER stress plays a critical role in inflammation and cell death, leading to the development of OM and points to ER stress inhibition as a potential therapeutic approach for the prevention of OM.

RNA-seq analysis of potential lncRNAs for age-related hearing loss in a mouse model.

Age-related hearing loss (AHL) is an important health problem in the elderly population. Its molecular mechanisms have not been fully elucidated. In this study, we analyzed the differential expression of lncRNAs and mRNAs in the cochleae of six-week-old and one-year-old C57BL/6J mice through RNA-seq analysis. We found 738 and 2033 differentially expressed lncRNAs and mRNAs, respectively, in these two groups (corrected P < 0.05). We focused on the intersection of known genes associated with hearing loss and differentially expressed mRNAs in RNA-seq. There are 34 mRNAs in this intersection, which include all 29 mRNAs enriched in the sensory perception of sound (GO: 0007605). We selected 11 lncRNAs that are predicted to regulate the 34 mRNAs to validate their expression levels in animal and cellular models of AHL by qRT-PCR. Among these lncRNAs, four were significantly different in both animal and cellular models of AHL, and the lncRNA NONMMUT010961.2 was the most markedly different. Knocking down lncRNA NONMMUT010961.2, we found the expression of oxidative stress and apoptosis-related gene Ar and hearing loss-related gene Hgf is significantly reduced in HEI-OC1 cells. Our results suggest that lncRNAs NONMMUT010961.2 may be associated with AHL and may thus lead to a new treatment for AHL.

Correlation between the rs7101 and rs1063169 polymorphisms in the FOS noncoding region and susceptibility to and prognosis of colorectal cancer.

BACKGROUND: The FOS gene is located on human chromosome 14q21-31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. METHODS: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan-Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. RESULTS: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131-1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111-1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues (P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS (P < .05). CONCLUSION: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.

Analysis of the expression of D-dimer, CD147 and miR203 and their correlation in gastric cancer.

OBJECTIVES: To evaluate the relationship of D-dimer, CD147 and miR-203, and detect the influence of these biomarkers on the pathological characteristics in patients with gastric cancer. METHODS: The patients with gastric cancer treated using radical gastrectomy between May 2013 and October 2017 were reviewed retrospectively. The expression of D-dimer, miR203 and CD147 was measured for all the patients, and the clinical data including age, gender, tumor size, tumor differentiation, invasion depth, lymphatic metastasis, TMN stage, and pathological type were retrieved and analyzed. The study was carried out in affiliated Yidu Central Hospital of Weifang Medical College, Qingzhou, China. RESULTS: Two hundred sixty patients with gastric cancer were included. The patients with tumor metastasis, larger tumor diameter, lower differentiation, lymphatic metastasis, deeper invasion, and higher TMN stage presented with a significantly higher D-dimer and CD 147 expression, but the level of the two biomarkers didn't show a significant difference in patients with different pathological type, gender and age. Compared with CD147 and D-dimer, miR203 presented with different characteristics of expression. In addition, the expression of miR203 was negatively correlated with CD147 and D-dimer, and there was a positive correlation between CD147 and D-dimer in patients with gastric cancer. CONCLUSION: In this study, a close correlation of D-dimer, miR203 and CD147 was found, and these three biomarkers should be screened in gastric cancer patients.

Comparative efficacy and safety of bridging strategies with direct mechanical thrombectomy in large vessel occlusion: A systematic review and meta-analysis.

BACKGROUND: Whether bridging strategies[intravenous thrombolysis (IVT) + mechanical thrombectomy (MT)] are superior to mechanical thrombectomy alone for large vessel occlusion(LVO) is still uncertain. A systematic review and meta-analysis was conducted to investigate and evaluate comparative efficacy and safety of bridging strategies vs direct MT in patients with LVO. METHODS: The PubMed, EMBASE and Cochrane library databases were searched to evaluate the efficacy and safety of bridging strategies with direct MT in LVO. Functional independence, mortality, symptomatic intracranial hemorrhage (sICH) and successful recanalization were assessed. The risk ratio (RR) and its 95% confidence interval (CI) were calculated. RESULTS: The proportion of patients who received MT + IVT was significantly higher in functional independence and successful recanalization rate than MT alone patients. However, pooled results showed that the mortality of patients who received MT + IVT was significantly lower than that of MT alone patients. Moreover, no significant differences were observed in the incidence of sICH between the 2 groups. CONCLUSION: The findings of our meta-analysis confirmed that bridging strategies improved functional outcomes, successful recanalization rate and reduced mortality rates. Moreover, the incidence of sICH showed no differences between the bridging strategies and MT alone treatments. However, the conduct of high-quality randomized clinical trials that directly compare both strategies is warranted.