Objectives Long non-coding RNAs (lncRNAs) have been identified as key regulators in the development of atherosclerosis, which is a major cause of ischemic stroke. However, to date, there are no reports on the association between lncRNA gene variation and the risk of ischemic stroke. Therefore, we assessed the association between H19 and MALAT1 gene polymorphisms and susceptibility to ischemic stroke in a northern Chinese Han population. Methods In our study, we genotyped four genetic variations in lncRNA-H19 and -MALAT1 (rs217727, rs2251375, rs619586, and rs3200401) in a case–control study of 567 ischemic stroke patients and 552 control subjects. Results We found that the TT genotype of the rs217727 polymorphism within H19 was significantly associated with increased risk of ischemic stroke in our northern Chinese Han population (odds ration (OR) = 1.519, 95% confidence interval (CI) = 1.072–2.152, p = 0.018). Stratified analysis based on stroke subtype revealed that the increased risk was more evident in small vessel ischemic stroke (OR = 1.941, 95% CI = 1.260–2.992, p = 0.02). Individuals with the TT genotype had a 1.941 times higher risk of small vessel ischemic stroke when compared with the subjects of CC + CT. These correlations remained after adjusting for confounding risk factors of stroke (OR = 1.913, 95% CI = 1.221–2.998, p = 0.005). However, there was no significant association between H19 rs2251375 or MALAT1 rs3200401 and ischemic stroke in either total population analysis or subgroup analysis. Conclusion In conclusion, our findings suggest that the H19 rs217727 gene polymorphism contributes to small vessel ischemic stroke susceptibility in the Chinese Han population and may serve as a potential indicator for ischemic stroke susceptibility.

Background: Stroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke.Methods: Relevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor.Results: Overall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility.Conclusions: Our study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention.

Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.

Objective: Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an important role in DN development. However, until now, the association between genetic polymorphisms and DN risk has remained unknown. We performed a systematic review, meta‐analysis, and trial sequential analysis (TSA) of the association between all genetic polymorphisms and DN risk.Methods: Relevant published studies examining the relationship between all genetic polymorphisms and DN were obtained based on a designed search strategy up to 28 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess overall pooled effects of genetic models as well as in subgroup analyses. Sensitive analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results.Results: We conducted a systematic review of a total of 1256 articles, and then 106 publications reporting on 136 polymorphisms of 76 genes were extracted. We performed 107 meta‐analyses on 36 studies involving 12,221 subjects to derive pooled effect estimates for eight polymorphisms. We identified that ACE I>D, MTHFR 1298A/C, GPx‐1 rs1050450, and CAT ‐262C/T were associated with DN, while MTHFR C677T, GSTM1, GSTT1, and IL‐10 ‐1082G/A were not. Sensitivity analysis, funnel plot, and Egger’s test displayed robust results. Furthermore, the results of TSA indicated sufficient sample size in studies of ACE, GPx‐1, GSTM1, and IL‐10 polymorphisms.Interpretation: Our study assessed the association between ACE I>D, MTHFR C677T, MTHFR 1298A/C, GPx‐1 rs1050450, CAT ‐262C/T, GSTM1, GSTT1, and IL‐10 ‐1082G/A polymorphisms and DN risk. We hope that the data in our research study are used to study DN genetics.

Objective: X‐linked Charcot‐Marie‐Tooth type 1 (CMTX1) is an inherited peripheral neuropathy caused by mutations in the gap junction beta 1 (GJB1) gene, which encodes the connexin32 protein. A small number of patients withGJB1mutations present with episodic neurological dysfunction and reversible white matter lesions, which has not been adequately reported. Here, we aim to enable clinicians to further understand this particular situation through systematically reviewing all published relevant cases.Methods: We conducted a comprehensive search of the PubMed electronic database for medical literature relevant to CMTX1 patients with episodic neurological dysfunction and then fully analyzed the general information, clinical manifestations, and characteristics of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and nerve conduction study (NCS).Results: We identified 47 cases of CMTX1 associated with episodic central nervous system (CNS) dysfunction from 38 publications. CMTX1 patients experienced episodic CNS deficits at a young age, ranging from infancy to 26 years, and 45 (95.7%) of them were male. The CNS symptoms manifested as facial, lingual, or limb weakness in 44 (93.6%), dysarthria or dysphagia in 39 (83.0%), facial or limb numbness in 15 (31.9%), and ataxia in 10 (21.3%) patients. The duration of episodic symptoms ranged from 3 minutes to 6 months. Thirty (63.8%) CMTX1 cases have reported obvious predisposing factors, among which the most common factors were infection or fever (27.7%), travel to high altitude (12.8%), and intensive exercise (8.5%). As for brain MRI, most abnormal signals were found in bilateral deep white matter (88.9%) and corpus callosum (80.0%). In addition, most of the NCS results were abnormal, including prolonged latency, reduced amplitude, and slowed conduction velocity. The motor nerve conduction velocity (MNCV) of median nerve was the most detectable and valuable, ranging from 25 to 45 m/s.Interpretation: We have reported the most comprehensive summary of the demographic and clinical profile from 47 CMTX1 patients with episodic CNS deficits and provided new insight into the phenotype spectrum of CMTX1. We hope that our study can help clinicians make early diagnosis and implement the best prevention and treatment strategies for CMTX1 patients with episodic CNS deficits.