NDVI-Based Lacunarity Texture for Improving Identification of Torreya Using Object-Oriented Method

Normalized Difference Vegetation Index （NDVI） is a very useful feature for differentiating vegetation and non-vegetation in remote sensed imagery. In the light of the function of NDVI and the spatial patterns of the vegetation landscapes, we proposed the lacunarity texture derived from NDVI to characterize the spatial patterns of vegetation landscapes concerning the ＂gappiness＂ or ＂emptiness＂ characteristics. The NDVI-based lacunarity texture was incorporated into object-oriented classification for improving the identification of vegetation categories, especially Torreya which was the targeted tree species in the present research. A three-level hierarchical network of image objects was defined and the proposed texture was integrated as potential sources of information in the rules base. A knowledge base of rules created by classifier C5.0 indicated that the texture could potentially be applied in object-oriented classification. It was found that the addition of such texture improved the identification of every vegetation category. The results demonstrated that the texture could characterize the spatial patterns of vegetation structures, which could be a promising approach for vegetation identification.

Lacunar infarction with leukoaraiosis may aggravate cognitive dysfunction

This study semi-quantitatively analyzed the effects of leukoaraiosis.Patients with moderate or severe lacunar infarction were found to exhibit low scores on the Montreal Cognitive Assessment Scale （F=12.02,P=0.000）,and prolonged P300 Cz2.0 latency （F=16.04,P=0.000）.Correlation analysis revealed that the occurrence of leukoaraiosis was negatively correlated with Montreal Cognitive Assessment scores （r=-0.416,P=0.000）,and positively correlated with P300 Cz2.0 latency （r=0.538,P=0.000）.These findings indicate that leukoaraiosis aggravates cognitive impairment in patients with lacunar infarction,such that more severe leukoaraiosis is associated with more severe cognitive decline.

Fractal lacunarity of trabecular bone and magnetic resonance imaging:New perspectives for osteoporotic fracture risk assessment

Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density(BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture(TBA) during aging and osteoporosis. Magnetic resonance imaging(MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest fractal analysis as a promising approach to quantify morphofunctional changes in both aging and pathology. In this particular context, fractal lacunarity seems to be the proper tool to characterize TBA texture as it is able to describe both discontinuity of bone network and sizes of bone marrow spaces, whose changes are an index of bone fracture risk. In this paper, an original method of MRI texture analysis, based on TBA fractal lacunarity is described and discussed in the light of new perspectives for early diagnosis of osteoporotic fractures.

Sodium ozagrel and atorvastatin for type 2 diabetes patients with lacunar cerebral infarction

BACKGROUND The main pathological factor of cerebral infarction is atherosclerosis,which is the pathological process of chronic inflammatory diseases such as vascular smooth muscle hyperplasia,inflammatory cell infiltration,extracellular matrix increase,and thrombosis.At present,the focus of clinical treatment is anti-platelet aggregation and improving blood status,and current research is limited to improving symptoms only.AIM To observe the effect of sodium ozagrel and atorvastatin on type 2 diabetes patients with lacunar cerebral infarction.METHODS Eighty-two patients with type 2 diabetes and lacunar cerebral infarction admitted to our hospital from January 2018 to February 2020 were equally categorized into two groups according to their treatment method.The control group was administered atorvastatin,and the observation group was administered sodium ozagrel combined with atorvastatin.The National Institutes of Health stroke scale(NIHSS)score,activities of daily living(ADL)score,blood glucose,lipid levels,inflammatory factors,high-mobility group box 1(HMGB1)levels,paraoxonase-1(PON-1)levels,erythrocyte sedimentation rate(ESR),and macrophage migration inhibitory factor(MIF)levels were recorded before and after treatment.The total effective rate and adverse reaction rate of the two groups were analyzed.RESULTS The total effective rate of the observation group(94.00%)was significantly higher than that of the control group(80.00%)(χ2=3.998;P=0.046).The blood glucose indexes,total cholesterol levels,triglyceride levels,low-density lipoprotein cholesterol levels,high-sensitivity C-reactive protein levels,interleukin-1βlevels,tumor necrosis factor-αlevels,HMGB1 Levels,ESR,MIF levels,platelet aggregation rates,and plasma viscosity of the two groups decreased after treatment;however,high-density lipoprotein cholesterol and PON-1 Levels increased after treatment.After treatment,the blood glucose indexes;blood lipid indexes;inflammatory factors;HMGB1,PON-1,and MIF levels;ESR;platelet aggregation rate;and plasma viscosity of the observation group were better than those of the control group(P<0.05).After treatment,all patients in the observation group had higher ADL scores and lower NIHSS scores than those in the control group(P<0.05).CONCLUSION Sodium ozagrel with atorvastatin can reduce inflammatory reactions;regulate ESR and HMGB1,PON-1,and MIF levels;control blood glucose and lipid indexes;and alleviate nerve injury without increasing adverse effects of atorvastatin alone.

Spatial Structure Characteristics Detecting of Landform based on Improved 3D Lacunarity Model

The spatial structure characteristics of landform are the foundation of geomorphologic classification and recognition.This paper proposed a new method on quantifying spatial structure characteristics of terrain surface based on improved 3D Lacunarity model.Lacunarity curve and its numerical integration are used in this model to improve traditional classification result that different morphological types may share the close value of indexes based on global statistical analysis.Experiments at four test areas with different landform types show that improved 3D Lacunarity model can effectively distinguish different morphological types per texture analysis.Higher sensitivity in distinguishing the tiny differences of texture characteristics of terrain surface shows that the quantification method by 3D Lacu-narity model and its numerical integration presented in this paper could contribute to improving the accuracy of land-form classifications and relative studies.

Association of ALOX5AP and PDE4D with the risk of lacunar infarct in people from Jiangsu Province,China

The genes for 5-1ipoxygenase activating protein （ALOX5AP） and phosphodiesterase 4D （PDE4D） have been demonstrated as susceptibility genes for lacunar in the Icelandic and Pakistani populations, but little is known about the role of these genes in Chinese populations. The present study utilized polymerase chain reaction and ligase detection reaction to detect single nucleotide polymorphisms （SNPs） in 280 consecutive stroke patients and 258 unrelated population-based controls from Nanjing, Jiangsu Province, China. The allele frequency, genotypes, and haplotypes of the two SNPs （rs456009 and rs966221） in PDE4D were similar between the two groups. However, A allele frequency of rs4073259 （A/G） and rs4769055 （A/C） in the ALOX5AP gene exhibited differences in two groups, and especially the haplotype of the SNP was significantly different between the two groups. Results suggested that the ALOX5AP gene might be involved in lacunar infarct, while PDE4D gene was not a risk factor for lacunar infarct in individuals from Jiangsu Province, China.

Correlative factors of cognitive impairment in patients with lacunar infarcts

Objective To study the relationships between cognitive impairment in patients with lacunar infarcts and quantitative CT measures and to determine the independent correlative factors of cognitive impairment.Methods Neuropsychological examination was conducted for 128 patients with acute lacunar infarct.Number,location,and volume of infarcts,cerebral atrophy index and severity of white matter lesions(WMLs) were measured and recorded.Results The number of lacunar infarcts in cognitive impairment (CI) group was significantly larger than that in cognitive normal(CN) group.Mean width of sulcus and sylvian fissure,index of frontal horn and ventricular-brain ratio(VBR) were significantly different in both groups.There were more patients with 3 grades or 4 grades WMLs in CI group(62%) than those in CN group(22%).The total volume of lacunar infarcts showed no statistically significant difference.Logistic regression analysis indicated that the number of lacunar infarcts in frontal subcortex and thalamus,the volume of infarcts in anterior periventricular white matter,width of cerebral sulcus and sylvian fissure were correlated with cognitive impairment respectively.Additionally,age and education were correlative factors of cognitive impairment in patients with lacunar infarct.Conclusion Correlative factors of cognitive impairment in patients with lacunar infarct are not merely one feature,but a combination of infarct features(number,location,and volume),cortical atrophy and host factors(age and education).

Correlation of ischemic ophthalmopathy with lacunar infarction

AIM:To investigate the correlation of ischemic ophthalmopathy(IO)with lacunar infarction(LI),an ischemic lesions in the cerebrovascular system.METHODS:Totally 204 cases of IO without any nervous system symptom and previously diagnosed LI served as the observational group.All 204 cases without IO,nervous system symptoms and previous LI served as the control group.Age and sex between the two groups matched well.LI was diagnosed by magnetic resonance imaging(MRI)and the results of the two groups were statistically analyzed and compared.RESULTS:IO included 174 eyes of 156 patients with non-arteritis anterior ischemic optic neuropathy(NAION),42 eyes of 36 patients with central retinal artery occlusion(CRAO)or branch retinal artery occlusion(BRAO)and 12 eyes of 12 patients with ocular ischemia syndrome(OIS).The detection rate of LI(72.54%)in IO group was obviously higher than that(15.68%)in the control group(P<0.001).IO was positively correlated with LI(r=0.573,P<0.05).In addition,most infarction sites located in the basal ganglia(67.57%),which were not the vital areas of cerebrum and not easy to be found due to their small size.The majority of those first visited IO patients(72.54%)without nervous system symptom and previously diagnosed LI had already suffered from LI.CONCLUSION:According to our studies,there is a positive correlation between IO and LI.IO can be used as an important predictor for the present of LI,especially obvious signs of the patient.

The relation between prognosis and nocturnal blood pressure variation in hypertensive patients with lacunar infarct

Objective We conducted a study using MRI and ambulatory blood pressure monitoring(ABPM) to determine whether an in-apporpriately low nocturnal blood pressure, or an excess fall in nocturnal blood pressure, might be responsible for lacunar infarct. Method ABPM and Casul blood pressure(CBP) were examined in 35 hypertentives with lacunar infarct(LI)and 33 hypertentives without lacunar infarct as control group. Results There is no significant difference of CBP between two groups. But the mean nighttime systolic blood pressure (nSBP) and diastolic blood pressure (nDBP) in patients with lacunar infarct were significantly smaller than in patients without lacunar infarct. The ratio of nSBP/dSBP and nDBP/dDBP in SI were smaller than in control group respectively. Conclusions The results indicate that an inap-propriately low nocturnal blood pressure, or an excessive fall in nocturnal blood pressure, is associated with lacunar infarct. It is necessary not only to control high blood pressure but also to pay attention to circadian changes of blood pressure during the course of anti-hypertensive treatment.

A case of paradoxical brain embolism presenting as a typical lacunar stroke

A 59 year old white male presented with a clinical picture typical of lacunar stroke. However, a thorough diagnostic work up showed that the most probable mechanism of stroke was paradoxical brain embolism through a patent foramen ovale. The clinical-neuroradiological mismatch that ultimately lead to the correct interpretation is discussed.

Pure motor stroke as the most frequent lacunar syndrome: A clinical update

Pure motor stroke(PMS), also known as pure motor hemiparesis, is the most common of any lacunar form(between one half and two thirds of cases, depending on the series). In an acute stroke registry, 733 patients presented a lacunar infarct and PMS accounted for 12.7%(n = 342) of all first-ever stroke patients and for 48% of all lacunar syndromes. The posterior limb of the internal capsule, corona radiata, and pons are the most frequent brain topographies. Infarcts in the mesencephalus or medullary pyramid have been exceptionally reported. This present update is focused on the clinical evidence and mechanisms underlying the relationship between PMS and different stroke etiologies.

Promoting lacunar bone regeneration with an injectable hydrogel adaptive to the microenvironment

Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical applications.The SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no gap.Moreover,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,respectively.In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway.The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells.Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and angiogenesis.Meanwhile,SMS hydrogel was proved to be antibacterial,especially for gram-negative bacteria.Furthermore,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone formation.Thus,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Vitamin D deficiency and increased inflammatory factor intercellular cell adhesion molecule-1 indicate severe leukoaraiosis in northern China

Background and objective:Commonly plaguing in the frigid zone of the world,vitamin D deficiency,as indicated by low levels of 25-hydroxyvitamin D,exacerbated inflammatory responses and impaired endothelial function.Leukoaraiosis(LA)is a prevalent cause of cognitive dysfunction in the elderly and is potentially associated with inflammatory responses.This study aimed to investigate the impact of vitamin D on the severity of LA.Methods:Patients with LA were categorized based on 3.0 T brain MRI findings into mild(N=43),moderate(N=40),or severe groups(N=29)using the Fazekas scale(scoring 1-6).A control group consisting of 41 healthy individuals was included.Serum fibrinogen C,homocysteine,plasma 25-hydroxyvitamin D,and intercellular cell adhesion molecule-1(ICAM-1)levels were measured using ELISA.Results:All LA severity groups exhibited lower plasma 25-hydroxyvitamin D levels compared to the control group,with a more pronounced decrease observed as LA severity increased.Low plasma 25-hydroxyvitamin D was identified as an independent risk factor for LA(P<0.05)according to Multiple logistic regression analysis.Additionally,a negative association was observed between 25-hydroxyvitamin D and vascular inflammatory factor ICAM-1.Conclusions:Disease severity positively correlated with levels of the inflammatory marker ICAM-1,worsening as plasma 25-hydroxyvitamin D concentration decreased.Low 25-hydroxyvitamin D emerged as an independent risk factor for LA,potentially exacerbating the inflammatory response.These findings suggest 25-hydroxyvitamin D supplementation as a potential therapeutic approach for LA.

腔隙性脑梗死合并脑微出血的危险因素与脑白质病变的相关性

目的 探讨腔隙性脑梗死(LI)合并脑微出血(CMBs)的危险因素及与脑白质病变(WML)的关系。方法 于2020年3月至2022年6月在海南省老年病医院收集LI患者134例,根据磁敏感加权成像(SWI)检测CMBs,分为CMBs组(49例)和非CMBs组(85例),利用脑白质病变量表评分(WMLs)分析LI患者脑白质病情情况与CMBs相关性,采用Logistic回归模型分析LI患者并发CMBs的危险因素。结果 134例LI患者合并CMBs发生率为36.57%(49/134例)。CMBs组WML发生率、WMLs评分明显高于非CMBs组(P<0.05);多因素Logistic回归分析显示,血尿酸、高血压史、高密度脂蛋白(HDL)、WML发生率和WMLs评分是LI患者发生CMBs的独立影响因素。且CMBs病灶数量与WMLs评分存在明显正相关(r=0.412,P<0.05)。结论 LI患者发生CMBs发生影响因素众多,控制血压、血脂水平以及降低血尿酸对于预防LI患者发生CMBs具有重要意义,且脑白质病变程度与CMBs严重程度紧密相关。

老年腔隙性脑梗死患者血清微小RNA-377和微小RNA-137水平及临床意义

目的分析老年腔隙性脑梗死(LI)患者血清微小RNA(miR)-377、miR-137水平及临床意义。方法选择2021年2月至2022年12月哈励逊国际和平医院收治的老年LI患者248例作为LI组,另选择同期来我院体检的健康者110例作为健康组;根据美国国立卫生研究院卒中量表(NIHSS)评分将老年LI患者248例分为神经缺损组60例(≥2分)和无神经缺损组188例(<2分)。检测血清miR-377、miR-137水平;用Pearson相关性分析和Spearman相关性分析;logistic回归分析老年LI患者神经缺损影响因素;ROC曲线评估血清miR-377、miR-137水平对老年LI及神经缺损诊断的预测价值。结果LI组血清miR-377、miR-137水平低于健康组(P<0.01)。miR-377和miR-137联合评估老年LI的曲线下面积(AUC)为0.782(95%CI:0.735~0.824),高于二者单一检测(P<0.01)。神经缺损组脑动脉硬化、血红蛋白降低、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)1、IL-6、IL-17、C反应蛋白(CRP)、改良的Rankin量表(mRS)评分高于无神经缺损组(P<0.05,P<0.01),血清miR-377、miR-137水平低于无神经缺损组(0.61±0.25 vs 0.89±0.28,0.61±0.24 vs 0.85±0.27,P<0.01)。血清miR-377与miR-137水平呈正相关(P<0.01);血清miR-377、miR-137水平与TNF-α、IL-6、CRP、mRS评分均呈负相关(P<0.01)。miR-377、miR-137、TNF-α、IL-6、CRP是老年LI患者神经缺损的影响因素(P<0.01)。miR-377、miR-137联合评估老年LI患者神经缺损的AUC为0.812(95%CI:0.758~0.859),高于二者单一检测(P<0.05,P<0.01)。结论血清miR-377、miR-137水平在老年LI及其神经缺损患者血清中表达较低,检测其水平具有一定临床预测价值。

多发腔隙性脑梗死后血管性认知障碍的发生情况及影响因素分析

目的探讨多发腔隙性脑梗死后血管性认知障碍发生的独立风险因素。方法采用回归分析研究多发腔隙性脑梗死患者的年龄、文化程度、婚姻状况、民族、吸烟史、饮酒史、运动状况、饮食状况、家族痴呆史、家族高血压史、家族脑卒中史、家族糖尿病史、合并心脏病、合并高血压、合并高血脂、合并糖尿病、脑梗死位置和NIHSS评分对多发腔隙性脑梗死后血管性认知障碍发生的影响。结果450例患者中40例(8.89%)发生血管性认知障碍。年龄、婚姻状况、运动状况、家族痴呆史、家族脑卒中史、合并高血压、合并高血脂、脑梗死位置和NIHSS评分是多发腔隙性脑梗死后血管性认知障碍发生的独立风险因素(P<0.05)。结论年龄、婚姻状况、运动状况、家族痴呆史、家族脑卒中史、合并高血压、合并高血脂、脑梗死位置和NIHSS评分对多发腔隙性脑梗死后血管性认知障碍的发生有显著影响,应在临床实践中加以重视,以制定有效的干预措施。

基于孟德尔随机化方法研究血清尿酸水平与脑小血管病之间的因果关系

目的:探究血清尿酸(SUA)水平是否与脑小血管病(CSVD)存在因果关系。方法:从已发表的全基因组关联研究汇总数据获得SUA、腔隙性脑梗死(LI)、白质高信号(WMH)、各向异性分数(FA)和平均弥散率(MD)的数据,筛选出与SUA强相关(F>10)的单核苷酸多态性(SNPs)作为工具变量,用逆方差加权法、MR-Egger、加权中位数法方法进行因果分析,利用MR-Egger截距法和Cochran's Q检验进行异质性和水平多效性检验。结果:逆方差加权法表明SUA与LI(OR=1.086,95%CI 0.959~1.230,P=0.193)、WMH(OR=1.010,95%CI 0.956~1.066,P=0.725)、FA(OR=1.058,95%CI 0.848~1.320,P=0.617)和MD(OR=1.009,95%CI 0.790~1.288,P=0.943)无关,敏感性分析结果显示无异质性和水平多效性。结论:目前MR研究表明SUA水平与CSVD之间不存在因果关系,但仍需规范化、大样本的临床研究和基于大规模GWAS的MR研究更全面评估它们之间的关联性。

腔隙性脑梗死患者脑白质病变情况与缺氧诱导因子1α相关性研究

目的:探究腔隙性脑梗死(LACI)患者脑白质病变情况与缺氧诱导因子1α(HIF-1α)的相关性。方法:收集196例LACI患者为研究对象,患者均完成MRI检查,并采用Fazekas量表评估纳入者脑白质病变情况;同时留取患者入院确诊时静脉血样,用于测定血清HIF-1α、半胱氨酸蛋白酶-3(Caspase-3);分析血清HIF-1α与脑白质病变情况的关系。结果:纳入者中72.45%出现脑白质病变,其中42.96%轻度病变,33.80%中度病变、23.24%重度病变。与非脑白质病变组相比,病变组患者年龄和高血压占比明显增大,血清HIF-1α和Caspase-3水平明显升高(均P<0.05)。脑白质不同程度病变者收缩压和血清HIF-1α和Caspase-3水平比较差异具有统计学意义(均P<0.01),重度病变者明显高于中度病变者,中度病变者高于轻度病变者(均P<0.05)。Logistic回归分析显示,收缩压和血清HIF-1α、Caspase-3水平均是影响LACI患者脑白质病变程度的危险因素(均P<0.05)。受试者工作特征(ROC)曲线分析显示,血清HIF-1α对LACI患者脑白质病变发生及重度脑白质病变均具有一定预测价值(AUC=0.840、0.874)。结论:LACI伴有脑白质病变患者体内HIF-1α呈高表达状态,且其表达水平升高与脑白质病变加重有关。

儿童重症肺炎支原体肺炎致不同类型脑梗死3例

总结3例儿童重症肺炎支原体肺炎致腔隙性脑梗死、大脑中动脉下干梗死、分水岭脑梗死的患儿临床特征及诊治结局。3例患儿均因发热、咳嗽为主诉收入院。住院期间出现活动不利等神经系统症状,完善头部影像学后确诊为脑梗死。病例1,男,5岁,腔隙性脑梗死同时合并有心房血栓及上肢动脉血栓。病例2,男,5岁,大脑中动脉下干梗死;病例3,女,4岁,分水岭脑梗死。病例2、3在行纤维支气管镜后出现神经系统症状。3例患儿D-二聚体水平均异常升高。肺炎支原体感染急性期可致各种类型脑梗死,不同类型脑梗死存在不同的致病机制。肺炎支原体肺炎诊疗过程中需检测D-二聚体水平、及时完善心脏超声,术前注意患儿出入量及灌注水平,避免脑梗死的发生。