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新生儿坏死性小肠结肠炎课件_9

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新生儿坏死性小肠结肠炎ppt 新生儿坏死性小肠结肠炎 新生儿坏死性小肠结肠炎9 新生儿坏死性小肠结 新生儿坏死性小 新生儿坏死性小肠结肠炎课件
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单击此处编辑母版标题样 式 单击此处编辑母版副标题样式 * * 1 1 新生儿坏死性小肠结肠炎 诊治新进展 Ø张宇和 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 新生儿坏死性小肠结肠炎(Neonatal necrotizing enterocolitis ,NEC) l临床上以腹胀、呕吐、便血为主要表现; l腹部X线平片以动力性肠梗阻,肠壁囊样积 气,门静脉积气为特征; l病理以回肠远端和结肠近端的坏死为特点。 l本病在近20年来有增加趋势,主要是NICU 的建立,早产儿特别是极低出生体重儿存活 率增高,故本病发生率也随之增加。在极低 出生体重儿中,死于NEC的患儿占早产儿死 亡总数的10%。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l极低出生体重儿的NEC发病率 荷兰 6% ( 4%疑诊、 2%确诊) 美国 27% (17%疑诊、10%确诊) 加拿大 10% (确诊) 澳大利亚 13% (17%疑诊、10%确诊) l据报道,住院病人中新生儿NEC总发病率 为4% (1~6%) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 危险因素 1.早产 2.围产期窒息 3.感染 4.RDS 5.脐动静脉插管 术 6.低温 7.休克 8.缺氧 9.先天心 (如PDA等) 10.红细胞 增多症 11.贫血 12.快速换血 13.先天性胃 肠道畸形 14.喂养过多 、增加过快 15.鼻—空肠 喂养 16.高渗配方 乳 17.高渗性 药物 18.NEC流行 期间的住院 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【病因与发病机制】 目前对目前对NECNEC的病因与发病机制还未完全明了,的病因与发病机制还未完全明了, 认为认为NECNEC是未成熟肠道受细菌及其他多种因素单一是未成熟肠道受细菌及其他多种因素单一 或共同作用引起的粘膜病理改变。或共同作用引起的粘膜病理改变。 l l早产早产 ØØ免疫因素免疫因素 新生儿特别是早产儿肠内新生儿特别是早产儿肠内T T淋巴细胞数量淋巴细胞数量 少,分泌型少,分泌型IgAIgA也少,故免疫功能低下,病原体及其也少,故免疫功能低下,病原体及其 毒素易进入肠道内,发生感染。毒素易进入肠道内,发生感染。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society Ø肠上皮屏障不成熟 不成熟的肠道对高分子物质有 较高的通透性,因此新生儿肠道对细菌等病原体 也易通透,促进细菌附着于肠上皮。当肠粘膜屏 障受破坏时,肠内细菌可穿过肠壁进入血液或肠 系膜淋巴结,引起败血症。 Ø肠腔发育不成熟 分泌的胃酸较少,小肠表面微绒 毛少,各种消化酶分泌少,酶的活性低,对各种 毒素的水解能力下降,故肠道易受损害。胃肠蠕 动能力差,食物易滞留,使细菌易滋长,造成食 物发酵、肠胀气。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l l喂养过度喂养过度 大多数发生于人工喂养的早产儿。大多数发生于人工喂养的早产儿。 ØØ加奶过快,如配方奶增加的速度加奶过快,如配方奶增加的速度40~60ml/kg.D40~60ml/kg.D,总,总 量量150ml/kg.D150ml/kg.D,则,则NECNEC发生率增加。发生率增加。 ØØ奶液配制过浓,渗透压过高,足月儿奶液配制过浓,渗透压过高,足月儿460mosm/L460mosm/L、、 早产儿早产儿400mosm/L400mosm/L可损伤肠粘膜致坏死。可损伤肠粘膜致坏死。 ØØ高渗药物溶液(消炎痛、维生素高渗药物溶液(消炎痛、维生素E E、茶碱等)进入胃、茶碱等)进入胃 肠道可能损伤肠粘膜。肠道可能损伤肠粘膜。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l感染 Ø目前不少学者认为细菌感染是产生NEC的主要原因。 Ø与本病有关的有克雷白氏杆菌、埃希氏大肠杆菌、绿脓杆菌和 一些其他肠道致病力不高的细菌,还有病毒与真菌〔见表〕。 细菌病毒真菌 埃希氏大肠杆菌轮状病毒曲霉菌 克雷白氏杆菌冠状病毒毛霉菌 绿脓杆菌 阴沟杆菌 沙门氏菌 表皮葡萄球菌 金黄色葡萄球菌 梭状芽孢杆菌 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society Ø新生儿出生后,肠内很快出现细菌,如因某些原因发生肠 内菌群失调,过度繁殖的某种肠道菌群较易侵入肠粘膜引 起炎症。炎症介质可激活血小板活化因子(PAF)、肿瘤 坏死因子(TNF)和其他细胞因子,与前列腺素等参与诱 发NEC的共同通道导致肠道损伤。 Ø内毒素也参与NEC发病机理的共同通道。内毒素激活巨噬 细胞产生TNF及PAF,二者协同诱发肠道损伤。PAF可激 活白细胞三烯(LT)释放,引起局部动脉收缩致缺血。 Ø克雷白氏杆菌等细菌在糖类存在下迅速繁殖,发酵产生氢 气,肠壁出现囊样积气。 Ø部分持不同意见学者认为细菌感染虽然是发生NEC的必要 条件,但它不是NEC原发的原因,而是肠壁在窒息后受到 缺血缺氧损伤的继发感染。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l缺氧缺血 Ø一向认为围产期窒息,肠壁缺血缺氧是发病的重 要原因。因为新生儿窒息时,为了保证重要的生 命器官心脑等供血,减少肠道血管血流,致使肠 壁缺血缺氧,肠粘膜受损害,最终导致NEC。 Ø有人持不同意见,他们认为肠壁缺血缺氧可能是 其他因素引起的继发改变。例如细菌与内毒素侵 入肠粘膜引起炎症,损伤了肠粘膜毛细血管及其 内皮细胞,产生NO减少,不能维持血管正常张力 而收缩,导致肠壁粘膜缺血性损伤,产生NEC。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 血管内皮细胞血管内皮细胞血管平滑肌细胞血管平滑肌细胞 L-L-精氨酸精氨酸 NOS NOS L- L-瓜氨酸瓜氨酸 NADP+O NADP+O 2 2 NONO 可溶性鸟可溶性鸟 苷环化酶苷环化酶 GTPGTP cGMPcGMP 蛋白激酶蛋白激酶 蛋白磷酸化蛋白磷酸化 CaCa++ ++ 血管舒张血管舒张 NONO扩张血管平滑肌的机制扩张血管平滑肌的机制 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l再灌注损伤 新生儿窒息、呼吸衰竭、休克、低血压、 低体温、脐血管插管、快速交换输血、红 细胞增多症、先天心(如PDA)等都可引 起血循环的不稳定性,使机体或某一器官 缺血缺氧,恢复后可产生血流的再灌注, 而加重组织的损伤。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 新进展 最近国外研究NEC的发病机制中,发现血 小板活化因子(PAF)在NEC的发病过程 中起关键作用。 PAF的生物学特征: PAF是一种具有广泛生物活性的内源性磷脂 介质,其合成受磷脂酸A2调节。 PAF在PAF-乙酰水解酶(PAF-AH)作用下 ,乙酰基水解为羟基,完全失去活性 。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society PAF的生物效应: Ø促进血小板、中性粒细胞聚集; Ø释放氧自由基,TNF-α,白介素、花生四 烯酸及其代谢产物; Ø促使血管扩张和通透性增加; Ø参予血栓形成、低血压、肺动脉高压,胃 肠粘膜损害等疾病的炎症反应过程。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ØPAF受体(PAF-R)是一种G蛋白偶联受体 ,PAF与细胞膜表面PAF-R结合后,通过磷 脂酰肌醇降解途径,使细胞内钙离子浓度 升高,引起PAF的生物效应。 Ø动物实验表明:注射大剂量PAF,大鼠的空 肠、回肠可迅速发生肠坏死,而PCR检测 发现回肠PAF-R基因转录最高,而空肠为 回肠的56%。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society PAF引起肠坏死的作用机制 Ø粘附分子 Ø活性氧 Ø白三烯、儿茶酚胺、补体和磷酯酶A2( PLA2) ØTNF-α表达与NF-kB转录 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society Ø粘附分子 在PAF作用下,可产生以多形核白细胞( PMN)活化、PMN与血管内皮细胞粘附为 特征的急性炎症反应,而粘附分子白细胞β2 整合素在炎症反应中促使两者的牢固的粘 附与聚集,这表明粘附分子在肠损伤中的 重要作用。 Ø活性氧 PAF可通过蛋白水解作用促使XD向XO转化 ,XO利用分子氧 ,高活性超氧化物,在肠 损伤发挥作用。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society Ø白三烯、儿茶酚胺、补体和磷酯酶A2(PLA2 ) PAF是一种血管舒张剂,但大剂量PAF却诱 导产生白三烯和去甲肾上腺素,而导致血管 收缩,引起肠损伤。 PAF激活补体系统,使C5参与NEC的形成。 PLA2参与多种炎症反应,并调节PAF合成。 ØTNF-α表达与NF-kB转录 在PAF和TNF-α介导下,LPS(脂多糖)发 挥作用,可激活NF-kB转录,上调多种促炎 因子,产生急性炎症反应。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 小结 早产、缺氧、肠道喂养,细菌感染均能引 起体内PAF水平增高,PAF通过激活其他炎 性介质和细胞因子,在NEC连锁反应中起 重要作用。因此,开发和应用选择性强、 效价高、副作用小的PAF拮抗剂,可成为临 床预防和治疗NEC的最有效途径。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【病理】 l病理变化主要部位在回肠未端与升结肠近端 ,肠腔充气,肠粘膜呈斑片状或大片状坏死 ,肠壁可有不同程度积气,可见粘膜水肿、 出血、溃疡。镜下粘膜呈凝固性坏死、粘膜 下层有弥漫性出血或坏死,严重者整个肠壁 坏死,可伴有肠穿孔和腹膜炎。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【临床表现 】 本病多见于早产儿,男多于女,生后2~3周内发病, 以2~10天为高峰,也有24小时内发病或生后2个月才发 病。轻症只表现为腹胀及胃潴留,重者伴有中毒性肠麻 痹。 l腹胀 常为首发症状,先有胃潴留然后出现腹胀如鼓, 腹壁发亮,伴有腹膜炎时,腹壁发红发亮,肠鸣音减少 或消失。 l呕吐 呕吐物可呈咖啡样或带胆汁。 l腹泻、血便 开始时为水样便,1~2天后可排血便,可 呈鲜血、果酱样或便中带血丝。轻症仅有隐血阳性。腹 泻次数不一,一天多达10多次不等。 l全身症状 体温可有低热或不升、拒食、反应差,常出 现呼吸暂停,心动过缓,严重时可出现紫绀、黄疸、皮 肤出现 瘀斑、酸中毒及休克。 l并发症 严重时可并发败血症、肠穿孔、腹膜炎。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【 X线检查 】 l肠管呈中度扩张,肠腔内可能有多个细小液平面 ; l肠壁内出现积气,表现为局部密集的小泡沫透亮 区,称为肠壁囊样积气; l门静脉积气影,自肝门脉处呈向上的树枝样透亮 影,可于4小时内消失; l气腹则表示肠穿孔; l腹腔积液表示腹膜炎。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【 NEC的分期】 Bell等根据临床表现和X线将NEC分Ⅲ期(具体见表)。 分期 全身症状消化道症状X线表现 Ⅰ疑诊期 ⅠA体温不稳、呼吸暂停、心 动过缓 、萎糜 胃潴留、轻度胀 气、呕吐、大便 隐血阳性 正常或肠扩张 , 轻度肠梗阻 ⅠB 同上 同上,便中有鲜 血 同上 Ⅱ确诊期 ⅡA 同上 同上,加肠鸣 音 消失,伴或不伴 腹部轻度压痛 肠扩张 、肠梗阻 、肠积 气 NEC的Bell分期标准 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 分期 全身症状消化道症状X线表现 ⅡB 同上,加轻度代谢性酸 中毒和血小板减少 同上,加肠鸣 音 消失,腹部中度 压痛,伴或不伴 腹部蜂窝织 炎或 右下腹包块 同上ⅡA,加门 脉积气、伴或不 伴腹水 Ⅲ进展期 ⅢA 病情严重 肠完整 同ⅡB,加低血压、心 动过缓 、严重呼吸暂停 伴呼吸性和代谢性中毒 ,DIC和中性粒细胞减少 同上,加弥漫性 腹膜炎体征,腹 部重度压痛和腹 胀 同ⅡB,加明显 的腹水 ⅢB 病情严重 肠穿孔 同ⅢA 同ⅢA 同ⅡB,加气腹 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【实验检查】 l血常规 白细胞增高,核左移,血小板减少。 l大便常规与培养 镜下可见数量不等的红细胞与 白细胞,隐血试验阳性,细菌培养阳性率约30- 40%,以埃希氏大肠杆菌、克雷白氏杆菌、绿脓 杆菌多见。 l血培养 大多为革兰氏阴性杆菌,与大便培养结果 大致相同。 l血生化 严重时可有代谢性酸中毒,电解质紊乱, 败血症时可有CRP持续升高。 l腹腔液培养 腹腔穿刺或手术时取腹腔液作培养, 阳性率高。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l腹部B超检查:有时可见肝实质及门脉内间 歇出现气体栓塞;有时还可 见腹水及炎性团块。 l红细胞膜表面的隐性抗原(TFC)阳性,有 助于早期诊断。 l有报道,NEC最早症状出现前的8~28小时 内呼吸中的氢气(H2)含量显著升高。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【诊断与鉴别诊断】 l l凡新生儿特别是早产儿,围产期有明显缺氧史或其他诱凡新生儿特别是早产儿,围产期有明显缺氧史或其他诱 因应密切观察,有精神面色改变,出现腹胀腹泻时应立因应密切观察,有精神面色改变,出现腹胀腹泻时应立 即做腹部平片并行大便隐血试验,这对早期诊断有帮助即做腹部平片并行大便隐血试验,这对早期诊断有帮助 ,必要时可做腹部平片动态观察,这是确诊,必要时可做腹部平片动态观察,这是确诊NECNEC最重要最重要 的方法。的方法。 l l临床上应与下列疾病相鉴别:临床上应与下列疾病相鉴别: ØØ中毒性肠麻痹;中毒性肠麻痹; ØØ机械性小肠梗阻;机械性小肠梗阻; ØØ先天性巨结肠;先天性巨结肠; ØØ肠扭转;肠扭转; ØØ自发性胃穿孔;自发性胃穿孔; ØØ胎粪性腹膜炎;胎粪性腹膜炎; ØØ新生儿出血症。新生儿出血症。 可根据可根据NECNEC临床典型症状与体征,放射影像学检查进行临床典型症状与体征,放射影像学检查进行 鉴别诊断。鉴别诊断。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【预防】 l提倡母乳喂养:新鲜母乳有多种免疫因子,而且 母乳中的PAF-AH活性较高,是预防NEC的最好 乳品。 l对早产儿特别是低出生体重儿,应采用谨慎的每 次少量增加进乳量的喂养方法。对易患NEC的新 生儿每日增加的奶量不能超过40~60ml/ kg ,每 日总奶量不能超过150ml/kg。 lNEC流行期保持环境的清洁卫生,做好消毒隔离 措施,防止交叉感染。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l药物 Ø肾上腺皮质激素:对产前母亲应用皮质激素有预 防NEC作用,有报道对母亲产前未接受皮质激素 治疗的早产儿在产后进行激素治疗(地塞米松 2mg/kg.D,IV)可明显降低NEC的发病率及死亡 率。 Ø免疫球蛋白:口服免疫球蛋白制品(IgA与IgG)可 降低NEC发病率。但静脉用丙球无预防作用。 Ø口服抗菌素:尽管有口服氨基糖甙类抗生素预防 NEC的报道,但对其疗效有争议,大多主张不用 ,以免产生耐药菌株,反而有害。 有报道新生儿在开始喂养前48小时预防性口服万 古霉素可降低NEC发病率。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【治疗】 l禁食 Ø对可疑的NEC的患儿应开始禁食,禁食时间应根 据病人的临床情况而确定。轻症5~10天,重症 需要禁食2周或更长,同时立即插胃管,进行胃肠 减压。 Ø待腹胀消失后可开始试喂,以新鲜母乳为宜,或1 :1配方奶,从少量(3~5ml/次)开始,逐渐加 量。喂奶前先抽胃内容物,如有积乳,可停喂1次 ,或减少原来喂奶量。 Ø在喂养过程中,如有腹胀,呕吐等症状复发,需 再禁食。至症状消失后再从头开始喂奶,有时需 要反复多次。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l静脉补充液体与营养 禁食期间液体与营养物质需从 静脉补充,液体量约为100~150ml/kg.D,病初热卡为 50kcal/kg.D,逐渐增至100~120kcal/kg.D。营养物质 包括葡萄糖、氨基酸、脂肪乳,电解质与微量元素等 。 l抗生素 可根据药敏试验结果选用敏感抗生素,针对 肠道杆菌可应用广谱的β-内酰胺类抗生素如青霉素 ,与氨基糖甙类抗生素如庆大霉素联合使用,氨苄青 霉素(100~200mg/kg.D)静滴、氧哌嗪青霉素 (100~200mg/kg.D)静滴、庆大霉素(3~5mg/kg.D)静 滴,丁胺卡那霉素(8~10mg/kg.D) ,耐药者可用第三 代头孢类如头孢哌酮,头孢他啶(50~100mg/kg.D)静 滴,或头孢曲松(50~80mg/kg.D)静滴。对厌氧菌 ,首选甲硝唑(15~30mg/kg.D)静滴。如培养为耐 药金黄色葡萄球菌或表皮葡萄球菌,可选用万古霉素 (20~30mg/kg.D)静滴。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l抗休克治疗 出现休克时可用生理盐水,低 分子右旋糖酐(10ml/kg)、血浆(10ml/kg)、 白蛋白(1g/kg)扩容,多巴胺、多巴酚丁胺( 均为5 ~ 10μg/kg.min)维持血压。 l肾上腺皮质激素 地塞米松(0.5~1mg/kg, 每6~8小时一次),可阻滞血管舒缓素、 防止产生激肽以终止内毒素休克的发展。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l支持疗法 全血(10ml/kg)、血浆(10ml/kg) 或静脉丙种球蛋白(400 ~ 1000mg/kg) 。 l其他 出现呼吸衰竭时要用呼吸机支持治疗 ,要维持酸碱平衡,纠正电解质紊乱,贫 血者要输血。输血或血浆时应注意输血后 发生溶血的危险。 lPAF拮抗剂为今后治疗NEC最有效途径。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society l外科指征 Ø发生气腹时,提示有肠穿孔,除个别小量气腹且 病情有好转者,均应立即手术治疗; Ø腹膜炎症状体征明显,腹壁有明显红肿时,常示 有肠坏死或有脓肿,应考虑手术治疗。 Ø内科保守治疗后病情继续恶化,酸中毒、休克不 能纠正,甚或出现DIC时。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【预后】 本病病死率仍甚高,约10-50%,存活者 中有5-30%可发生肠狭窄,多发生于回肠 结肠连接处,或由于肠切除过多产生短肠 综合征导致严重营养障碍,术后需继续随 访。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 谢 谢 !
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