miR-138靶向调控SIRT1表达及其对膀胱癌细胞增殖和凋亡的影响

目的 探讨微小RNA-138（miRNA-138）在膀胱癌细胞中的表达情况,并研究其对膀胱癌细胞增殖和凋亡的影响及其可能的靶基因。方法 采用实时定量PCR（QPCR）法检测膀胱癌细胞T24和正常膀胱上皮细胞SV-HUC-1中miR-138的表达水平。将T24细胞分为3组：未转染组、miR-138对照组（转染阴性对照片段）和miR-138转染组（转染miR-138 mimics）。采用MTT法检测细胞的增殖情况,流式细胞术检测细胞的凋亡情况;Western blotting检测细胞中沉默信息调节因子1（SIRT1）蛋白的表达水平;双荧光素酶报告基因实验验证miR-138与SIRT1间的靶向关系。结果 膀胱癌T24细胞中miR-138的表达量为0.57±0.19,低于SV-HUC-1细胞的1.00±0.26（P＜0.05）。miR-138转染组的miR-138表达量为2.59±0.67,高于未转染组的1.00±0.36和miR-138对照组的1.08±0.49（P＜0.05）。miR-138转染组T24细胞的增殖率显著低于未转染组和miR-138对照组（P＜0.05）。 转染48 h后,miR-138转染组的细胞凋亡率为（29.8±1.9）％,高于未转染组的（5.8±1.2）％和miR-138对照组的（7.7±0.9）％（P＜0.05）。miR-138转染组SIRT1的相对表达量为0.59±0.22,低于未转染组的1.00±0.35和miR-138对照组的1.20±0.42（P＜0.05）。双荧光素酶报告基因实验证明SIRT1是miR-138的直接作用靶点。结论 miR-138在膀胱癌细胞中低表达,可能通过靶向SIRT1调控膀胱癌细胞的增殖和凋亡。     

Do Adults with Stroke have Altered Interhemispheric Inhibition? A Systematic Review with Meta-Analysis

ObjectiveInterhemispheric inhibition is an important cortical mechanism to support motor control. Altered interhemispheric inhibition has been the target of neuromodulation interventions. This systematic review investigated the evidence for altered interhemispheric inhibition in adults with unilateral neurological conditions: stroke, amyotrophic lateral sclerosis, cerebral palsy, complex regional pain syndrome, traumatic brain injury, and cerebral palsyMethodsWe pre-registered the protocol and followed PRISMA guidelines. Five databases were systematically searched to identify studies reporting interhemispheric inhibition measures in unilateral neurological conditions and healthy controls. Data were grouped according to the measure (ipsilateral silent period and dual-coil), stimulated hemisphere, and stage of the condition (subacute and chronic).Results1372 studies were identified, of which 14 were included (n = 226 adults with stroke and 161 age-matched controls). Ipsilateral silent period-duration was longer in people with stroke than in controls (stimulation of dominant hemisphere) regardless of stroke stage. Motor evoked potential was less suppressed in people with sub-acute stroke (stimulation of the unaffected hemisphere) than controls (stimulation of dominant hemisphere) and this reversed in chronic stroke.ConclusionDetection of altered interhemispheric inhibition appears to be dependent on the measure of interhemispheric inhibition and the stage of recovery.SignificanceRebalancing interhemispheric inhibition using neuromodulation is considered a promising line of treatment for stroke rehabilitation. Our results did not find compelling evidence to support consistent alterations in interhemispheric inhibition in adults with stroke.     

Predictors of silent hypoxia in hospitalized patients with COVID-19 in Japan

IntroductionSilent hypoxia (SH) is common in patients with coronavirus disease (COVID-19) in Japan and other countries. Early identification of SH is important as more treatment options for COVID-19 have become available. This study aimed to identify predictors of SH using a nationwide COVID-19 registry of hospitalized patients.MethodsAdult patients who were admitted to hospital with COVID-19 between January 2020 and June 2021 and who were hypoxic on admission (SpO₂: 70–93%), not transferred from another facility, and who did not have disturbance of consciousness, confusion, or dementia, were included. SH was defined as hypoxia in the absence of shortness of breath/dyspnea upon admission. Predictors of SH were identified using univariable and multivariable logistic regression.ResultsThe study included 1904 patients, of whom 990 (52%) satisfied the criteria for SH. Compared to patients without SH, patients with SH were older, more likely to be female, and had a slightly higher SpO₂ on admission. Compared to patients without SH, patients with SH had a lower prevalence of chronic lung disease (CLD) other than chronic obstructive pulmonary disease (COPD), asthma, and obesity. Multivariable analysis revealed that the independent predictors of SH were older age, a shorter interval from symptom onset to admission, higher SpO₂, and an absence of CLD or COPD.ConclusionsThe absence of underlying lung disease and older age were important predictors of SH. The results of this study, which is the largest such study reported to date in Japan, may help clarify the mechanism of SH.     

Frequencies of D19S433 silent alleles in a Japanese population of 1501 individuals and their effect on likelihood ratios calculated in kinship tests

Although silent alleles in D19S433 typing using the GlobalFiler PCR Amplification Kit have been reported, the exact frequency of the D19S433 silent alleles in population data of 1501 Japanese individuals, which are widely used for the assessment of Japanese STR typing results, is unclear. In this study, we examined the exact D19S433 silent allele frequency in this population data. We newly observed the G32A variant causing silent alleles at D19S433 in five samples. Combining them with data including 30 samples with the variant reported previously, we determined that the total frequency of the silent alleles (i.e. the frequency of the G32A variant) in the 1501 Japanese samples was 0.0117 (35/3002). Using the D19S433 allele frequency data, we evaluated the effect of presence/absence information for the D19S433 silent allele on kinship tests. Likelihood ratios (LRs) were calculated for both simulated parent–child and full sibling cases, revealing that the LR may change by approximately 10⁻² to 10³ fold when the presence/absence of the D19S433 silent allele is revealed in a kinship test. Therefore, if a sufficiently large or small LR is obtained, there is little need to determine the presence/absence of the D19S433 silent allele in Japanese kinship tests using GlobalFiler. This study will be beneficial for the assessment of Japanese human identification and kinship test results using GlobalFiler.     

高血压和高同型半胱氨酸血症与静止性脑梗死的相关性分析

目的 调查静止性脑梗死（silent brain infarction，SBI）在健康体检人群中的患病率，分析高血压、 高同型半胱氨酸血症（hyperhomocysteinemia，HHcy）与SBI的相关性。 方法 本研究为单中心横断面研究，前瞻性连续纳入2018年9月-2019年6月既往无明确神经系统 疾病的体检者，收集人口学信息，高血压、糖尿病、冠心病等血管危险因素，生活方式及生化检查 （包括血浆同型半胱氨酸）等资料。影像学医师采用盲法评价头颅MRI，判断是否存在SBI。按照是否 存在高血压和HHcy分为正常、单纯高血压、单纯HHcy、高血压合并HHcy 4组，采用单因素和多因素 Logistic回归分析高血压、HHcy与SBI的相关性。 结果 共纳入577名受试者，平均年龄52.0±10.4岁，女性252名（43.7%）。SBI患病率为8.8% （51/577），高血压、HHcy的患病率分别为20.5%（118/577）和27.6%（159/577），高血压合并HHcy 的患病率为8.3%（48/577）。单因素分析显示，单纯HHcy（OR 3.72，95%CI 1.69～8.18，P =0.002），单 纯高血压（OR 5.88，95%CI 2.59～13.3，P＜0.001），高血压合并HHcy（OR 7.66，95%CI 3.20～18.3，P ＜0.001）均增加SBI风险。校正混杂因素后，单纯HHcy（OR 2.55，95%CI 1.06～6.11，P =0.036），单 纯高血压（OR 3.97，95%CI 1.68～9.43，P =0.001），高血压合并HHcy（OR 3.64，95%CI 1.31～10.1， P =0.013）也均与SBI风险升高有关。单因素分析中高血压和HHcy存在交互作用（P＜0.001）；在多因素 分析中，高血压和HHcy的交互作用差异无统计学意义（OR 0.29，95%CI 0.08～1.09，P＞0.05）。 结论 在健康体检人群中，SBI是一种常见头部影像学改变，高血压和HHcy均与SBI相关。     

隐匿性鼻窦综合征的CT及MRI诊断

目的 探讨隐匿性鼻窦综合征的CT和MRI表现.方法 回顾性分析经临床证实的8例隐匿性鼻窦综合征的CT和MRI平扫资料,观察病变部位和征象.结果 8例均单侧发病,累及眼眶、上颌窦、鼻腔与额面部.CT表现:8例眼眶底壁下凹、眼眶下直肌周围脂肪间隙比对侧增厚;8例上颌窦前后壁内缩、窦腔体积缩小及患侧上颌窦黏膜增厚.6例上颌窦后壁周围肌肉脂肪间隙较对侧增宽.8例鼻中隔偏曲并双侧颧面部不对称、患侧颧骨向内凹陷.MRI表现:8例眼球向下移位、眼眶底壁向下塌陷并下直肌周围脂肪间隙扩大;8例上颌窦黏膜增厚;5例患侧中鼻道扩张伴中鼻甲萎缩;6例窦口鼻道复合体阻塞;8例患侧颧面部不同程度凹陷、相应脂肪组织增厚.结论 患侧眼眶底壁下陷、眼球下移,窦壁骨质凹陷引起的上颌窦体积缩小、黏膜增厚以及额面部凹陷是隐匿性鼻窦综合征较典型的影像学表现.     

The effect of lead exposure on expression of SIRT1 in the rat hippocampus

Based on how the silent information regulator 2 homolog 1 (SIRT1) regulates the cyclic AMP response element binding protein (CREB), which is the molecular switch of long-term memory that maintains cognitive function, it is postulated that the impact of lead (Pb) on SIRT1 is one of the mechanisms leading to Pb-induced cognitive and learning deficits. Hence, the purpose of this study was to investigate the effect of Pb exposure on the expression of SIRT1, and the reversion effect of resveratrol, which is an activator of SIRT1. We examined the effects of maternal rat ingestion of Pb in drinking water during gestation and lactation on the expression of SIRT1 and CREB in the hippocampus of their offspring at postnatal week 3 (PNW3) and 52 (PNW52), and then reexamined these effects in offspring after intragastric administration of resveratrol for 4 weeks. Pb exposure decreased SIRT1 and CREB phosphorylation in a dose-dependent manner in the rat hippocampus at both PNW3 and 52, and resveratrol reversed those losses. These results indicated that SIRT1 might be a novel target to prevent Pb neurotoxicity.     

On the estimation of silent period thresholds in transcranial magnetic stimulation

ObjectiveWe evaluated the induction of corticospinal silent period (SP) using transcranial magnetic stimulation (TMS) at stimulation intensities normalized to resting motor threshold (rMT) or silent period thresholds (SPTs). The aim was to reduce the characteristic inter-individual variation in SP measurements in healthy population to improve the sensitivity of such measurements.MethodsThe cortical representation area of the right hand musculature of 12 healthy subjects was stimulated with navigated TMS with varying stimulating intensities. Subsequently, the individual SPTs for eliciting SPs of 20, 30, and 50 ms in duration were determined from the input–output characteristics.ResultsWhile SPT for 20 and 50 ms SPs differed from rMT, the SPT for 30 ms was similar to rMT. Nevertheless, the inter-individual variation in SP duration was reduced significantly at 120% of SPT30 when compared with SP durations obtained at 120% of rMT.ConclusionsInter-individual variation in the SP duration decreases when applying TMS at stimulation intensities normalized to the individual SPTs instead to the rMT. This makes the SP duration more specific to inhibition and less affected by changes in cortical excitability.SignificanceUse of individual SPTs may improve the sensitivity of the SP measures in studies with inter-individual design.     

老年高血压无症状靶器官损害与血压昼夜节律的研究

目的 研究老年高血压患者（EH）血压昼夜节律与无症状脑梗死、微量白蛋白尿、左心室肥厚的关系。方法 对35例老年杓型EH患者及47例非杓型EH患者进行血压监测、头颅MRI、超声心动图及尿白蛋白、纤维蛋白原检查。结果 老年非杓型EH组中无症状脑梗死、微量白蛋白尿及左心室肥厚的发生率显著高于老年的杓型EH组。结论 血压昼夜波动节律消失的老年EH患者其无症状靶器官损害较血压昼夜节律正常的EH患者明显。     

SIRT1在变应性鼻炎中的作用及其研究进展

变应性鼻炎是IgE介导的鼻黏膜的非感染性炎性疾病,Th1/Th2/Th17/Treg细胞的失衡是变应性鼻炎的重要免疫学特征。沉默信息调节因子2相关酶1(SIRT1)作为III类组蛋白去乙酰化酶,在DNA修复和凋亡、肌肉和脂肪分化、神经元增殖分化、代谢、炎症反应、氧化应激中发挥重要作用。目前关于SIRT1在变应性疾病中的研究主要集中在类风湿性关节炎、系统性红斑狼疮及哮喘中,对于其在变应性鼻炎中的研究较少,本文就近年来SIRT1在变应性鼻炎中的相关研究进展作一综述。