OBJECTIVE:To investigate whether rosmarinic acid (RA) confers in intro and vivo protective effects by specifically activating the peroxidase activity of PRDX1. METHODS:HepG2 cells were pretreated with RA and then treated with H2O2, LPS, or different pro-inflammatory cytokines to assess RA's anti-oxidant and anti-inflammatory activities. Primary hepatocytes were isolated from 6-week-old male PRDX1Cys52Ser mice and pretreated with RA and then treated with LPS to assess RA's anti-oxidant and anti-inflammatory activities in hepatocytes without PRDX1 peroxidase activity. In addition, 8-week-old male PRDX1Cys52Ser mice started to receive western diet (WD) feeding for 20 weeks to induce metabolic dysfunction associated steatohepatitis (MASH). In the meantime, daily injection of RA or Veh was carried out in these animals to evaluate the beneficial effects of RA on MASH and liver fibrosis using a variety of techniques. RESULTS:RA showed anti-oxidant and anti-inflammatory activities in HepG2 cells, while it lost these protective activities in primary PRDX1Cys52Ser mutant hepatocytes. In addition, RA treatment in WD-fed PRDX1Cys52Ser mice did not show any improvements in MASH and liver fibrosis compared with Veh treatment, which was also supported by unaltered expression of hepatic genes related to inflammation and fibrosis, as well as signaling activities of hepatic signal transducer and activator of transcription 1 and 3 (STAT1/3) after RA treatment. CONCLUSION:RA exerts both in vitro and in vivo beneficial effects by specifically activating the peroxidase activity of PRDX1.

Purpose: PCDH19 gene variants, termed PCDH19 clustering epilepsy, represent a distinct etiology of epilepsy. This study aimed to elucidate the clinical manifestations and explore the genotypes and phenotypes of children affected by PCDH19 clustering epilepsy. Methods: This retrospective study included medical history, magnetic resonance imaging, videoelectroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children's Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients. Results: The age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25-22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fevertriggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440-66.111)). Conclusion: In this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.

PURPOSE:PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. Our objective was to characterize the genotypes and phenotypes of PAFAH1B1-related epilepsy.METHODS:We conducted a comprehensive analysis of the medical histories, magnetic resonance imaging findings, and video-electroencephalogram recordings of 11 patients with PAFAH1B1 variants at the Neurology Department of Beijing Children's Hospital from June 2017 to November 2022.RESULTS:The age of onset of epilepsy ranged from 2 months to 4 years, with a median onset age of 5 months. Among these 11 patients (comprising 6 boys and 5 girls), all were diagnosed with lissencephaly type 1. Predominantly, generalized tonic-clonic and spasm seizures characterized PAFAH1B1-related epilepsy. Additionally, 10 out of the 11 patients exhibited severe developmental disorders. All patients exhibited de novo variants, with three individuals displaying 17p13.3 deletions linked to haploinsufficiency of PAFAH1B1. Four variants were previously unreported. Notably, three patients with 17p13.3 deletions displayed developmental delay and drug resistant epilepsy, whereas the single patient with mild developmental delay, Intelligence Quotient (IQ) 57 and well-controlled seizures had a splicing-site variant.CONCLUSION:The severity of the phenotype in patients with PAFAH1B1 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. These observations underscore the clinical heterogeneity of PAFAH1B1-related disorders, with most patients exhibiting developmental disorders. Moreover, the severity of epilepsy appears to be linked to genetic variations.

Abstract Background Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. Methods A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. Results This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869. Conclusion We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Peroxiredoxin 1 (PRDX1) is a potent antioxidant protein that displays a unique molecular chaperone activity. However, the role of overexpression of PRDX1 in colorectal cancer (CRC) was elusive. Herein, we found that the number of AOM/DSS-induced colitis-associated CRC in PRDX1 knockout mice was significantly lower than that in wild-type mice, concurrent with the downregulation of NRF2 and GPX4. Mechanistically, RNA sequencing results indicated that knockdown of PRDX1 resulted in a significant reduction of NRF2, which further triggered ROS-induced mitochondrial dysfunction and lipid peroxidation-induced ferroptosis in CRC cells. Notably, PRDX1 inhibited NRF2 degradation and promoted NRF2 nuclear translocation and consequently triggered the transcription of GPX4. Immunoprecipitation-mass spectrometry (IP-MS) and Co-immunoprecipitation (Co-IP) assays revealed that PRDX1 could function as a molecular chaperone binding to CUL3 to inhibit the ubiquitination of NRF2. Importantly, the binding of PRDX1 to CUL3 was enhanced by conoidin A but abrogated by PRDX1 Cys83Ser mutant. The inhibitory effects of silencing PRDX1 on CRC could be attenuated by NRF2 activation or ferrostatin-1 administration in vivo. Collectively, these results provide a new insight into the molecular chaperone activity of PRDX1 in triggering CRC progression through suppression of CUL3-mediated NRF2 degradation, suggesting PRDX1 Cys83 is a potential drug target in inhibiting CRC.

Laparoscopic distal gastrectomy (LDG) has become a common procedure for treating advanced gastric cancer (AGC) in China. However, there is uncertainty regarding its oncological outcomes compared to open distal gastrectomy (ODG). This study aims to compare the 3-year disease-free survival (DFS) rates among patients who underwent surgery for AGC in northern China. A multicenter, non-inferiority, open-label, parallel, randomized clinical trial was conducted to evaluate patients with AGC who were eligible for distal gastrectomy at five tertiary hospitals in North China. In this trial, patients were randomly assigned preoperatively to receive either LDG or ODG in a 1:1 allocation ratio. The primary endpoint was postoperative morbidity and mortality within 30 days and the secondary endpoint was the 3-year DFS rate. This trial has been registered at ClinicalTrials.gov (Identifier: NCT02464215). A total of 446 patients were randomly allocated to LDG (n = 223) or ODG group (n = 223) between March 2014 and August 2017. After screening, a total of 214 patients underwent the open surgical approach, while 216 patients underwent laparoscopic surgery. The 3-year DFS rate was 85.9

Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. The prevalence of SSAP was 9.2

OBJECTIVE:The neonatal and infantile period is the age group with the highest incidence of epilepsy, in which gene variants in sodium and potassium channels are an important etiology, so the sodium channel blocker class of antiseizure medications may be effective in the treatment of early onset epilepsy. This study aimed to summarize the efficacy and tolerability of oxcarbazepine (OXC) in the treatment of focal epilepsy in neonates and infants under 3 months of age.METHODS:A retrospective analysis of children with focal epilepsy onset within 3 months of age and treated with OXC in a tertiary pediatric epilepsy center in China was conducted. The efficacy, tolerability and influencing factors of OXC were evaluated.RESULTS:A total of 50 patients were enrolled, with a median age of epilepsy onset of 11.5 (2, 42) days. There were 32 cases of early infantile developmental and epileptic encephalopathy, 10 cases of self-limited neonatal or neonatal-infantile epilepsy, and 8 cases of focal epilepsy that could not be classified as epileptic syndrome. The median age of application of OXC was 47 (31, 66) days. The median follow-up time was 16.5 (10, 25) months, with 7 deaths. Thirty-eight cases (76.0 %) were effective with OXC treatment, including 28 cases (56.0 %) achieved seizure freedom. Of the 34 cases whose pathogenesis involved genetic factors, 19 cases with sodium/ potassium channel gene variants had higher effective and seizure-free rates than those with other gene variants. The most common adverse event was transient hyponatremia. 2 cases had rash and 2 cases had abnormal electrocardiogram, 3 of which discontinued OXC.SIGNIFICANCE:This single-center retrospective study suggests that OXC is effective and tolerable for the treatment of focal epilepsy in neonates and infants under 3 months of age. The efficacy of OXC is better in patients with sodium/ potassium channel gene variants.

探讨中国儿童遗传性痉挛性截瘫的临床和遗传特点。

Purpose The aim of this study was to compare the clinical characteristics of acute pancreatitis (AP) patients between those who developed pancreatic exocrine insufficiency (PEI) and those who did not, and to investigate the predictive factors of PEI. Patients and Methods From October 1st 2019 to July 30th 2021, AP patients admitted at our center were included. The fecal elastase-1 assay was adopted for PEI diagnosis. The clinical characteristics, treatments, and outcomes between the patients with and without PEI were analyzed. Results In total, 63 males and 42 females were included. There were 27 patients with mild AP, 54 with moderately severe AP, and 24 with severe AP. The median modified computed tomography severity index (MCTSI) was 6.000(4.000, 8.000). During the follow-up, 38 patients developed PEI after AP. The univariate analysis showed that higher ASA grade (P = 0.006), more severe AP (P = 0.000), the presence of multiple organ dysfunction syndrome (P = 0.030), higher MCTSI (P = 0.000), the development of infected pancreatic necrosis (P = 0.002) and local complications (P = 0.000), higher levels of triacylglycerol (P = 0.022), video-assisted retroperitoneal debridement intervention (P = 0.015), and longer intensive care unit stay (P = 0.044) were correlated with PEI development. Furthermore, the logistic regression analyses showed that MCTSI during hospitalization is an independent risk factor for PEI development during the AP recovery period. Conclusion ASA grade, severity of AP, multiple organ dysfunction syndrome, MCTSI, infected pancreatic necrosis, local complications, higher levels of triacylglycerol, video-assisted retroperitoneal debridement intervention, and longer intensive care unit stay were potentially associated with PEI development during the AP recovery period. High MCTSI was independently associated with the development of PEI during the AP recovery period, which may help alert to the possibility of PEI to help with its early detection and treatment.

BackgroundAromatic amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive neurometabolic disorder with heterogeneous phenotype, including hypotonia, movement disorders, autonomic dysfunction, and developmental delay. Here, we reported a Chinese patient with AADCD who was initially misdiagnosed with epilepsy.Case presentationThe proband was a 4-month-old Chinese girl, representing hypotonia, episodes of oculogyric crises with dystonia, and delayed developmental milestones. The patient was first misdiagnosed with epilepsy because of the similarity between episodes of oculogyric crisis and epileptic seizure. The accurate diagnosis of AADCD was established through analysis of neurotransmitters in cerebrospinal fluid (CSF). The genetic test confirmed the patient carried novel compound heterozygous mutations in the DDC gene:c.419G>A and c.1375C>T.ConclusionThis study reported a patient with AADCD who was initially misdiagnosed as epilepsy. Two novel missense mutations in the DDC gene were identified from the patient and her family. Little infants with epileptic-like attacks should consider AADCD. An accurate diagnosis of AADCD is essential for drug choice and patient management.

Abstract Objective To analyze the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC) and its influence on the distribution of lymph node metastasis at each lateral level of the neck to guide precise treatment of the lateral area. Methods The clinicopathological data of patients with PTC initially diagnosed and treated at our hospital from February 2014 to September 2021 were collected; the metastatic status of each lateral level was recorded, and correlations were analyzed. Results A total of 203 patients were enrolled in this study. There were 67 males and 136 females, with an average age of 41.1 years. In the lateral cervical area, lymph node metastasis was found at level IIa in 81 patients (39.9%); level III, 171 patients (84.2%); level IV, 122 patients (60%); and level Vb, 18 patients (8.9%). Correlation analysis showed that age (r = 0.198, P < 0.01) and sex (r = 0.196, P < 0.01) were weakly correlated with the number of positive lymph nodes in the central region. The tumor size (r = 0.164, P < 0.05) was weakly correlated with lymph node metastasis at level IV. The presence of multiple tumor foci was weakly correlated with lymph node metastasis at level IIa (r = 0.163, P < 0.05) and Vb (r = 0.143, P < 0.05). The tumor location (r = − 0.168, P < 0.05) was weakly correlated with lymph node metastasis at level III. The number of positive lymph nodes in the central region (r = 0.189, P < 0.01) was weakly correlated with lymph node metastasis at level IV. Binary logistic regression analysis showed that the risk of metastasis of multifocal tumors was higher than that of unifocal tumors by 1.958 times at level IIa (P = 0.021, OR = 1.958) and 2.929 times at level Vb (P = 0.049, OR = 2.929). The higher the tumor was located, the higher the risk of metastasis at level III (P = 0.014, OR = 0.563). Every additional positive lymph node in the central region increased the risk of metastasis at level IV by 1.126 times (P = 0.009, OR = 1.126). Conclusions For patients with pathological evidence of lateral metastasis, standard dissection of level IIa through Vb is recommended; selective dissection requires careful consideration. Patients with multifocal tumors have a high risk of metastasis at levels IIa and Vb, which requires special attention during the operation.

Backgrounds. The novel coronavirus disease 2019 (COVID-19) has caused a global pandemic. Pancreatic injuries have been reported in COVID-19 patients. The present meta-analysis was conducted to compare the morbidity and outcomes of AP between COVID-19 positive and negative patients. Methods. Databases including Cochrane Library, PubMed, and EMBASE were systematically searched (until July 3rd 2022). Studies with English abstracts comparing the severity and outcomes of AP between COVID-19 positive and negative patients were included. Mean differences or odds ratios with a 95% confidence interval were employed for assess variables. Risk of publication bias was assessed with funnel plots. Results. Data from 7 studies with a total of 2816 AP patients were included. COVID-19 positive was associated with higher incidences of pancreatic necrosis (OR = 1.65; 95% CI: 1.13 to 2.42, P = 0.01; P = 0.82 for heterogeneity) and persistent organ failure (OR = 6.87; 95% CI: 2.37 to 19.98, P = 0.0004; P = 0.12 for heterogeneity), especially cardiovascular failure (OR = 2.92; 95% CI: 1.66 to 5.14, P = 0.0002; P = 0.58 for heterogeneity) and acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) (OR = 3.03; 95% CI: 2.09 to 4.39, P < 0.00001; P = 0.20 for heterogeneity). COVID-19 infection induced a higher level of CRP (MD = 0.40; 95% CI: 0.16 to 0.64, P = 0.001; P < 0.00001 for heterogeneity) as well as coagulation disorders involving platelets, prothrombin time, activated partial thromboplastin time, and D-dimer (all P < 0.05). During hospitalization, COVID-19 positive was associated with higher ICU admission rate (OR = 2.76; 95% CI: 1.98 to 3.85 P < 0.00001; P = 0.47 for heterogeneity). COVID-19 positive AP was associated with a higher mortality rate (OR = 3.70; 95% CI: 2.60 to 5.25, P < 0.00001; P = 0.12 for heterogeneity). Discussion. The number of included studies is limited and none is RCT, thus the risks of publication and selective bias could not be ignored. COVID-19 deteriorated the severity and clinical outcomes of AP, with a high incidence of morbidity and mortality.

Melanocortin-4 receptor (MC4R) in paraventricular nucleus in hypothalamus (PVH) shows bidirectional characterization in modulating food intake and energy homeostasis. Here, we demonstrated that MC4R knock down (MC4R KD) in PVH could attenuate AMPA receptor (AMPAR) mediated postsynaptic responses by altering AMPAR GluA1 subunit phosphorylation via protein kinase A (PKA) dependent signaling cascade and simultaneously lead to rapid body weight gain. Further, PKA knock down (PKA KD) in PVH engendered similar electrophysiological and behavioral phenotypes as MC4R KD mice. Importantly, we observed that the reduction of AMPAR GluA1 expression not only led to attenuated synaptic responses but also caused body weight gain, suggesting that the aberration of synaptic responses may be one of the crucial pathogeny for obesity. Our study provided the synaptic and molecular explanations of how body weight is regulated by MC4R in PVH.

Aim To explore the clinical and genetic spectrum of hereditary spastic paraplegia (HSP) in Chinese children. Method This retrospective study was conducted between January 2014 and October 2021 in children clinically diagnosed with either pure HSP (pHSP) or complex HSP (cHSP). Results We investigated 45 children (32 males, 13 females; mean age [SD] at symptom onset 4 years [7 months]). clinically diagnosed with HSP and identified genetic causes in 35 patients. Most patients with autosomal dominant HSP had pHSP (16/18), whereas most patients with autosomal recessive HSP tended to have cHSP (14/16). SPG11 was the most common autosomal recessive subtype, followed by FA2H/SPG35, whereas SPAST/SPG4 was the most frequent cause of autosomal dominant HSP. Two patients with CPT1C mutations presented with a complex phenotype. Meanwhile, 10 patients were found to have likely pathogenic variants/variants of uncertain clinical significance in six genes related to HSP. Interpretation SPG11 and SPG4 were the most frequent subtypes in Chinese children with autosomal recessive HSP and autosomal dominant HSP. However, the prevalence of SPG4 was much lower than that in adults, which might be explained by the late onset of the disease. On the other hand, FA2H/SPG35 was common in our cohort, while it contributed to only a small proportion of adult cases, which might be explained by its rapid progression and early death in some patients. We also expanded the genetic and clinical spectra of SPG73.

Linezolid is an oxazolidinone antibiotic exhibiting efficacy against multidrug-resistant (MDR) Gram-positive-related infections. However, its population pharmacokinetic (PopPK) profile in critically ill Chinese children has not been characterized.

BACKGROUNDBiliary and hypertriglyceridemic acute pancreatitis (BAP and HTGAP) are two of the leading etiologies in China. Infected pancreatic necrosis (IPN) is a particular and noticeable condition in the late stage of these diseases; however, the influential correlated factors on IPN and how to predict IPN are unclear.METHODSIn this retrospective study, 1,116 patients whose diagnosis was BAP or HTGAP met the inclusion criteria among 1,746 enrolled cases. Clinical characteristics were carefully recorded for further investigation of the factors influencing IPN. During a 6-month follow-up, we analyzed bacterial spectra and postoperative indicators related to minimally invasive necrosectomy.RESULTSGallstones and hypertriglyceridemia were the most prevalent causes (52.6% vs. 11.3%). The participants with HTGAP were younger (40 vs. 52 years, P<0.001), had a higher rate of severe acute pancreatitis (SAP) (51.8% vs. 32.0%, P<0.001), and had a higher prevalence of multiple organ dysfunction syndrome (MODS) (26.4% vs. 19.0%, P=0.020) than BAP patients. More IPN cases were noted in the BAP group than in the HTGAP group [20.2% vs. 13.7%; odds ratio (OR): 1.598, 95% confidence interval (CI): 1.027 to 2.451; P=0.034]. Etiologies, C-reactive protein (CRP) levels, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and MODS were the factors influencing IPN. The bacterial spectra and the rates of major postoperative complications were not significantly different.CONCLUSIONSPatients with BAP more frequently developed IPN. Etiology was independently related to the occurrence of IPN. The APACHE II score, MODS, etiology, and CRP contributed to predicting IPN occurrence. Management of IPN substantially improved the prognosis.

Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti-inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high-fat diet (HFD)-induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD-fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin-treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin-induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.

With the rise in the aging global population, stroke comorbidities have become a serious health threat and a tremendous economic burden on human society. Current therapeutic strategies mainly focus on protecting neurons from cytotoxic damage at the acute phase upon stroke onset, which not only is a difficult way to ameliorate stroke symptoms but also presents a challenge for the patients to receive effective treatment in time. The brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the adult brain, which possesses a remarkable capability to repair brain damage. Recent promising preclinical outcomes have made BDNF a popular late-stage target in the development of novel stroke treatments. In this review, we aim to summarize the latest progress in the understanding of the cellular/molecular mechanisms underlying stroke pathogenesis, current strategies and difficulties in drug development, the mechanism of BDNF action in poststroke neurorehabilitation and neuroplasticity, and recent updates in novel therapeutic methods.

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase that is well known for its sensitivity to the environmental stress of a cell or an organism. It senses the external signals which are transmitted from membrane-bound receptors and induces downstream signaling cascades to exert its physiological functions. Rac1 is an important regulator of a variety of cellular processes, such as cytoskeletal organization, generation of oxidative products, and gene expression. In particular, Rac1 has a significant influence on certain brain functions like neuronal migration, synaptic plasticity, and memory formation via regulation of actin dynamics in neurons. Abnormal Rac1 expression and activity have been observed in multiple neurological diseases. Here, we review recent findings to delineate the role of Rac1 signaling in neurodevelopmental disorders associated with abnormal spine morphology, synaptogenesis, and synaptic plasticity. Moreover, certain novel inhibitors of Rac1 and related pathways are discussed as potential avenues toward future treatment for these diseases.