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PurposeThe purpose of the present study was to identify predictors of severe white matter hyperintensity (WMH) with obesity (SWO), and to build a prediction model for screening obese people with severe WMH without Nuclear Magnetic Resonance Imaging (MRI) examination.Patients subjects and methodsFrom September 2020 to October 2021, 650 patients with WMH were recruited consecutively. The subjects were divided into two groups, SWO group and non-SWO group. Univariate and Logistic regression analysis were was applied to explore the potential predictors of SWO. The Youden index method was adopted to determine the best cut-off value in the establishment of the prediction model of SWO. Each parameter had two options, low and high. The score table of the prediction model and nomogram based on the logistic regression were constructed. Of the 650 subjects, 487 subjects (75%) were randomly assigned to the training group and 163 subjects (25%) to the validation group. By resampling the area under the curve (AUC) of the subject’s operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram’s clinical usefulness. By resampling the area under the curve (AUC) of the subject’s operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram’s clinical usefulness.ResultsLogistic regression demonstrated that hypertension, uric acid (UA), complement 3 (C3) and Interleukin 8 (IL-8) were independent risk factors for SWO. Hypertension, UA, C3, IL-8, folic acid (FA), fasting C-peptide (FCP) and eosinophil could be used to predict the occurrence of SWO in the prediction models, with a good diagnostic performance, Areas Under Curves (AUC) of Total score was 0.823 (95% CI: 0.760–0.885, p

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with genetic and clinical heterogeneity characterized by spasticity and weakness of the lower limbs. It includes four genetic inheritance forms: autosomal dominant inheritance (AD), autosomal recessive inheritance (AR), X-linked inheritance, and mitochondrial inheritance. To date, more than 82 gene loci have been found to cause HSP, and SPG15 (ZFYVE26) is one of the most common autosomal recessive hereditary spastic paraplegias (ARHSPs) with a thin corpus callosum (TCC), presents with early cognitive impairment and slowly progressive leg weakness. Here, we reported a homozygous pathogenic variant in ZFYVE26. A 19-year-old Chinese girl was admitted to our hospital presenting with a 2-year progressive bilateral leg spasticity and weakness; early cognitive impairment; corpus callosum dysplasia; chronic neurogenic injury of the medulla oblongata supplied muscles; and bilateral upper and lower limbs on electromyogram (EMG). Based on these clinical and electrophysiological features, HSP was suspected. Exome sequencing of the family was performed by high-throughput sequencing, and an analysis of the patient showed a ZFYVE26 NM_015346: c.7111dupA p.(M2371Nfs*51) homozygous mutation. This case reported a new ZFYVE26 pathogenic variant, which was different from the SPG15 gene mutation reported earlier.

BackgroundMany studies among different ethnic populations suggested that angiotensin converting enzyme (ACE) gene polymorphisms were associated with susceptibility to Alzheimer's disease (AD). However, the results remained inconclusive. In the present meta-analysis, we aimed to clarify the effect of ACE polymorphisms on AD risk using all available relevant data.MethodsSystemic literature searches were performed using PubMed, Embase, Alzgene and China National Knowledge Infrastructure (CNKI). Relevant data were abstracted according to predefined criteria.ResultsTotally, 82 independent cohorts from 65 studies were included, focusing on five candidate polymorphisms. For rs1799752 polymorphism, in overall analyses, the insertion (I) allele conferred increased risk to AD compared to the deletion (D) allele (I vs. D: OR = 1.091, 95% CI = 1.007-1.181, p = 0.032); while the I carriers showed increased AD susceptibility compared with the D homozygotes (II + ID vs. DD: OR = 1.131, 95% CI = 1.008-1.270, p = 0.036). However, none of the positive results passed FDR adjustment. In subgroup analysis restricted to late-onset individuals, the associations between rs1799752 polymorphism and AD risk were identified using allelic comparison (OR = 1.154, 95% CI = 1.028-1.295, p = 0.015, FDR = 0.020), homozygotes comparison, dominant model and recessive model (II vs. ID + DD: OR = 1.272, 95% CI = 1.120-1.444, p < 0.001, FDR < 0.001). Nevertheless, no significant association could be revealed after excluding studies not in accordance with Hardy-Weinberg equilibrium (HWE). In North Europeans, but not in East Asians, the I allele demonstrated increased AD susceptibility compared to the D allele (OR = 1.096, 95% CI = 1.021-1.178, p = 0.012, FDR = 0.039). After excluding HWE-deviated cohorts, significant associations were also revealed under homozygotes comparison, additive model (ID vs. DD: OR = 1.266, 95% CI = 1.045-1.534, p = 0.016, FDR = 0.024) and dominant model (II + ID vs. DD: OR = 1.197, 95% CI = 1.062-1.350, p = 0.003, FDR = 0.018) in North Europeans. With regard to rs1800764 polymorphism, significant associations were identified particularly in subgroup of European descent under allelic comparison (T vs. C: OR = 1.063, 95% CI = 1.008-1.120, p = 0.023, FDR = 0.046), additive model and dominant model (TT + TC vs. CC: OR = 1.116, 95% CI = 1.018-1.222, p = 0.019, FDR = 0.046). But after excluding studies not satisfying HWE, all these associations disappeared. No significant associations were detected for rs4343, rs4291 and rs4309 polymorphisms in any genetic model.ConclusionsOur results suggested the significant but modest associations between rs1799752 polymorphism and risk to AD in North Europeans. While rs4343, rs4291 and rs4309 polymorphisms are unlikely to be major factors in AD development in our research.

Endothelial progenitor cells (EPCs) are multipotential stem cells considered to have immense clinical value for revascularization. However, the clinical application of EPCs has been hampered by their clinical potency in ischemic anoxic environments. This study aimed to explore the effect of microRNA-210 (miR-210) on EPCs under oxygen-glucose deprivation (OGD) conditions. We generated a model of EPCs cultured under OGD conditions to simulate ischemia and explore the expression of miR-210 in vitro. With longer exposure to hypoxia, we found that miR-210-3p expression was highly upregulated in OGD groups compared to that in controls from 4 to 24 h, but not miR-210-5p. We then transfected a miR-210-3p mimic and inhibitor into EPCs, and after 24 h, we exposed them to OGD conditions for 4 h to simulate ischemia. We detected miR-210 by real-time polymerase chain reaction (RT-PCR) and tested the proliferation, migration, and tube formation of normal EPCs and OGD-treated EPCs by CCK-8, transwell chamber, and Matrigel assays, respectively. The direct targets of miR-210-3p were predicted using miRWalk. Compared to that in normal EPCs, higher miR-210-3p expression was found in OGD-treated EPCs (p < 0.05). Moreover, upregulation of miR-210-3p was found to promote proliferation, migration, and tube formation in EPCs under normal and OGD conditions (p < 0.05), whereas down-regulation inhibited these abilities in OGD-treated EPCs (p < 0.05). Repulsive guidance molecule A (RGMA), a negative regulator of angiogenesis, was predicted to be a target of miR-210-3p. Accordingly, upregulation of miR-210-3p was found to inhibit its expression at the protein level in OGD-treated EPCs, whereas downregulation of miR-210-3p inhibited its expression (p < 0.05). A dual-luciferase reporter system confirmed that RGMA is a direct target of miR-210-3p. MicroRNA-210-3p overexpression enhances the angiogenic properties of OGD-treated EPCs by inhibiting RGMA.

Objective: To explore the correlationship among white matter hyperintensities (WMHs), miR-92a-3p and early-onset post-stroke depression (PSD).Methods: We recruited consecutively 238 patients with acute cerebral infarction and MRI examination in the Department of neurology, Ruijin hospital, Shanghai Jiaotong University School of Medicine. The diagnosis of early-onset PSD was made in accordance with DSM-IV criteria for depression in 2 weeks after stroke. Clinical information and assessments of stroke severity were recorded on admission. The analysis of plasma miR-92a-3p was performed using quantitative PCR at the same time. WMHs were evaluated by the Fazekas and Scheltens visual rating scales. The relationship among WMHs, miR-92a-3p and PSD were analyzed by SPSS 22.0 software.Results: Logistic regression demonstrated that periventricular WMHs (PVWMHs) in frontal caps was an independent risk factor with early-onset PSD (OR = 1.579, 95% CI: 1.040–2.397, p = 0.032). The age and numbers of lacunes were related to frontal PVWMHs. Plasma miR-92a-3p in the PSD group was higher compared with the non-depressed group. Receiver operating curve analysis revealed that miR-92a-3p could predict early-onset PSD with 90% sensitivity and 90% specificity. The higher miR-92a-3p trended toward association with greater frontal PVWMHs.Conclusion: Acute ischemic stroke patients with frontal PVWMHs or a high plasma miR-92a-3p at baseline were more likely to develop early-onset PSD. MiR-92a-3p might be involved in the white matter impairment and post-stroke depression.

Post-stroke depression (PSD) is one of the common complications after stroke. However, it is often overlooked in clinical practice. As a result, many patients have been misdiagnosed or never been diagnosed. Post-stroke depression directly affect cognitive function, late rehabilitation, functional recovery and the quality of life in stroke patients, and is closely related to the high recurrence rate, disability rate and mortality of stroke. In order to deepen the understanding of early and late PSD, this paper summarized recent progress of PSD at home and abroad, and made a brief introduction on the epidemiology, pathogenesis, influencing factors, screening and diagnosis, treatment and prevention of PSD. DOI: 10.3969/j.issn.1672-6731.2015.04.003

Objective To investigate the morbidity and associated factors of early onset depression after acute ischemic stroke, in order to improve its diagnostic rate and cure rate. Methods The depression symptoms of 150 patients with acute ischemic stroke were evaluated by using Hamilton Depression Rating Scale-17 (HAMD-17) 2 weeks after onset. According to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-Ⅳ) criteria, patients with HAMD-17 score ≥ 7 were diagnosed as post-stroke depression (PSD). Clinical data of those patients, including gender, age, education, laboratory indexes, predisposing factors, National Institute of Health Stroke Scale (NIHSS) score, Trial of Org10172 in Acute Stroke Treatment (TOAST) type, Oxfordshire Community Stroke Project (OCSP) classification, and concurrent carotid artery stenosis were recorded. Univariate and multivariate Logistic regression analysis was used to investigate the related factors of PSD. Results The morbidity of PSD in patients 2 weeks after stroke onset was 18% (27/150). Univariate and multivariate Logistic regression analysis showed triglyceride level (P = 0.042), neural function deficiency (P = 0.001) and concurrent carotid artery stenosis (P = 0.003) were independent risk factors for early onset PSD. Further subgroup analysis indicated concurrent carotid artery stenosis was the independent risk factor for PSD in non-minor stroke patients (P = 0.014). Conclusions Stroke patients with severe neurological deficits and carotid artery stenosis are susceptible to early onset PSD. DOI: 10.3969/j.issn.1672-6731.2015.03.007

DOI：10.3969/j.issn.1672-6731.2010.01.002

Background: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have been widely used in a variety of solid malignancies. Concerns have arisen regarding the risk of severe infections (≥grade 3) with use of these drugs, but the contribution of VEGFRTKIs to infections is still unknown. Methods: The databases of PubMed and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to December 2014. Summary incidences, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies. Results: A total of 16,488 patients from 27 randomized controlled trials were included. The risk of developing severe (Peto OR 1.69, 95% CI: 1.45-1.96, P<0.001) and fatal infections (Peto OR 1.78, 95% CI: 1.13-2.81, P=0.013) was significantly increased in patients treated with VEGFR-TKIs when compared to controls. Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls, with Peto ORs of 1.57 (95% CI: 1.30-1.88, P<0.001), 1.79 (95% CI: 1.29-2.49, P<0.001), 5.35 (95% CI: 1.47-19.51, P=0.011), and 3.68 (95% CI: 1.51-8.99, P=0.004), respectively. Additionally, VEGFR-TKIs significantly increased the risk of fatal sepsis (OR 3.66, 95% CI: 1.47-9.13, P=0.005) but not fatal pneumonia (OR 1.34, 95% CI: 0.80-2.25, P=0.26). Conclusion: The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs. [ABSTRACT FROM AUTHOR]