Curr Opin Clin Nutr Metab Care:肠易激综合征和饮食——2018年我们在哪里?

2018-02-17 张灵 | 消化客 江苏省人民医院消化科

过去五十年来,关于IBS饮食管理的研究数量急剧增加,研究干预的重点,规模和复杂程度各不相同。最初,许多研究调查膳食纤维在IBS管理中的作用,至少包括14项随机对照试验

肠易激综合征(IBS)是一种慢性功能性肠病,发病率高,患者负担重。在最近的罗马IV诊断标准中,IBS的定义更新为反复发作的的腹痛,伴有以下两项或两项以上:与排便有关;发作伴随排便频率的改变;发作伴随大便形态(外观)的改变。在罗马IV诊断标准中有4个主要的变化:1、由于感知的模糊和多变,删去了“不适”一词;2、将腹痛发作次数增加至每周至少1天(每月3天以上);3、“与排便有关”替代“排便改善”,因为许多人排便后无缓解;4、腹部疼痛不再需要与排便频率或形态的改变相吻合。在一项对美国、加拿大和英国5931人的调查中,更新的标准使得IBS的患病率降低至5.7%。

过去五十年来,关于IBS饮食管理的研究数量急剧增加,研究干预的重点,规模和复杂程度各不相同。最初,许多研究调查膳食纤维在IBS管理中的作用,至少包括14项随机对照试验。自20世纪90年代以来,关于益生菌(至少36项随机对照试验)和低发酵低聚糖,二糖,单糖和多元醇(FODMAP)饮食(至少10个随机对照试验)的研究越来越多。本文的目的是回顾关于使用各种饮食干预治疗IBS的证据的最新进展。

▌纤维和益生元

荟萃分析显示,车前草纤维对IBS患者有益,在需要治疗的7人中明显改善IBS症状,没有相关的不良事件。最近,一项103名IBS患儿的随机对照试验证明,与安慰剂相比,车前草引起疼痛频率的下降,尽管并没有显著降低绝对疼痛频率或疼痛严重程度。但是其他纤维类型(例如麸皮)的试验未能显示出一致的结果,其效应差异很大,这可能反映了在不同IBS亚型的不同效应,例如,对7项随机对照试验的系统回顾表明,各种纤维在便秘时增加排便频率和软化大便。因此,需要进行研究来确定其他纤维或纤维的组合是否有效,以及哪种IBS亚型可以从这种干预中受益。

最近,益生元被重新定义为“宿主微生物选择性利用的底物,赋予宿主健康益处”。近来发表的三项研究调查了益生元在IBS中的作用,在第一项研究中,IBS-D患者被随机分配接受带有低聚糖、多糖益生元混合物或安慰剂的成膜网状蛋白,研究结束时,试验组患者腹痛和胀气的百分比显著低于安慰剂组。同样,在第二项关于108例IBS患者的双盲试验中,与安慰剂相比,部分水解的瓜尔豆胶能够显著改善腹胀,但是没有其他肠道症状或排便的改善。最后一项随机对照试验在79名伴有直肠超敏反应的IBS患者中对5g/日短链低聚果糖(FOS)的效果进行了评估,并与安慰剂组相对比,尽管益生元组与安慰剂组相比焦虑评分显著降低,但两组之间的直肠不适、IBS症状、生活质量和肠道微生物组成均无差异,表明这种剂量的FOS对IBS的管理无效。

总之,没有足够的证据证明车前草以外的纤维对IBS的作用,主要是因为缺乏有力的研究,尽管最近对益生元的研究表明其在IBS中的作用有限。事实上,关于益生元在IBS中的治疗潜力存在争议,虽然益生元可能部分纠正IBS的生态失调,但越来越多的证据表明,一些益生元低聚糖(例如低聚果糖,菊糖)在高剂量下可能由于其快速发酵作用和结肠气体生成而使IBS症状恶化。

▌益生菌

益生菌是活的微生物,当施以足够的量时,对宿主健康有益。人们一直在关注益生菌对IBS的作用,已有9个不同的系统评价,包涵的试验可追溯到1989年(图1,编者注:原图请参见原文)。这些试验证明,某些菌种(例如双歧杆菌)对症状或腹痛的持续比其它菌种(例如埃希氏菌)更有效。最近,在这方面已经发表了10多项研究,包括离体,动物和人体研究。

例如,最近的两个荟萃分析研究了具体的益生菌菌种或菌株的影响,第一个研究了婴儿双歧杆菌在35624名IBS患者中的功效,提供患者单一的婴儿双歧杆菌或多种类益生菌补充剂(婴儿双歧杆菌作为其中的一部分),发现含有双歧杆菌菌株的多种类益生菌能显著减轻腹痛[SMD 0.22;95%置信区间(CI),0.03-0.41]和腹胀(SMD 0.30;95%CI,0.04-0.56),而单一菌株的婴儿双歧杆菌不影响IBS症状。另一个荟萃分析包括两项随机对照试验,在579例IBS患者中研究酿酒酵母CNCMI-3856的作用,结果显示,与安慰剂组相比,益生菌组的患者腹痛症状和粪便稠度显著改善(OR 1.5;95%CI,1.1-2.2),在以便秘为主的IBS亚组人群中也观察到腹痛和大便稠度的改善,但没有分析其他IBS亚组(如腹泻为主)的情况。

如表1所示(编者注:图表请参见原文),最近三项随机对照试验研究了其他益生菌菌种和菌株在IBS中的作用,结果相互矛盾。其中一项显示,长双歧杆菌NCC3001提高了IBS患者的生活质量,但无症状改善,并且还降低了抑郁评分,这与大脑激活模式的改变相关,表明边缘反应性降低。

综上,目前的证据表明特定的益生菌菌株在某些IBS症状中具有潜在的有益作用,然而,大多数研究存在相当大的局限性,如缺乏治疗意向分析和缺乏有效的评估工具,因此解释这些研究时需谨慎。

▌低FODMAP饮食

低FODMAP饮食限制了短链发酵碳水化合物,包括低聚糖(菊糖型果聚糖,低聚半乳糖)、二糖(乳糖)、单糖(超过葡萄糖的果糖)和多元醇的食用。在过去的十年,人们对低FODMAP饮食的关注逐渐增加,关于低FODMAP饮食干预的随机对照试验数量不断增多,规模不断扩大。尽管已经发表了至少10项研究,现有的综述只关注了低FODMAP饮食临床效应的最新进展,以及FODMAPs诱导症状的机制。

低FODMAP饮食的有效性

尽管营养干预试验通常容易控制,但很难设计出合适的安慰剂对照,解决方案包括喂养研究,这种研究可以实现严格控制,但缺乏临床设置的外部环境有效性和假饮食对照。最近发表了第一项关于低FODMAP饮食的随机安慰剂对照试验,在104名IBS患者中进行了一项用或不用益生菌的2×2析因设计试验,与假饮食组进行比较。低FODMAP组有57%的患者症状缓解,而假性饮食组为38%(P=0.051),症状缓解的比值是2.18(P=0.052),低FODMAP饮食显著减轻腹痛、腹胀、气胀和紧迫症状,改善部分生活质量。这种饮食还导致大便中的双歧杆菌减少,而双歧杆菌在服用益生菌的那些人中增加,这表明在低FODMAP饮食期间同时使用益生菌可能抵消对这些菌种的影响。

最近又有两项研究比较了低FODMAP饮食与高FODMAP饮食或低FODMAP饮食加短链低聚果糖的效应。第一项单盲随机对照试验显示,低FODMAP组饮食应答比例(72%)高于高FODMAP组(21%,P<0.009),但这项研究不包括治疗意向分析,使用高FODMAP饮食作为对照组可能实际上加重了症状,放大了低FODMAP饮食的效应。第二项研究比较了低FODMAP饮食+安慰剂与低FODMAP饮食+短链低聚果糖(即“正常FODMAP饮食”)的效应,低FODMAP组患者的症状缓解率(80%)较低FODMAP+短链低聚果糖组(30%;P=0.013)显著增加,恶心、呕吐和胃肠胀气显著减轻。

在饮食干预试验中克服对照组问题的另一种方法是与标准治疗进行比较,在2016年,一项随机对照试验比较了4周低FODMAP饮食与基于NICE指南的腹泻型IBS(IBS-D)患者标准膳食干预的效应。在低FODMAP组和NICE指南组中,症状充分缓解的患者比例没有差异(52%vs 41%,P=0.31),尽管低FODMAP组的腹痛应答者(51%)显著多于NICE指南组(23%,P=0.008)。另一个三臂随机对照试验在74名IBS患者中比较了6周低FODMAP饮食与指向肠道的催眠疗法与FODMAP饮食和催眠治疗相组合的临床效果,发现有大量的应答者,但各组间无差异。因此,与对照相比,低FODMAP饮食已被证明同IBS的一些其他干预一样有效。但是,要确保低FODMAP饮食的限制不会持续很长时间,并且为了减轻对营养摄入和肠道微生物群的影响,需将FODMAPs重新引入饮食中以形成耐受。目前还没有随机对照试验调查FODMAP的重新引入或低FODMAP饮食的长期有效性,但在最近一项在103名患者中进行的研究显示,57%的患者在重新引入FODMAP 6-18个月后报告有充足的症状缓解。

作用机制

近期少数研究试图去阐明可发酵碳水化合物引发IBS症状的可能机制。英国的一项研究包括了29名IBS患者和29名健康对照者,随机给予40g葡萄糖/果糖/菊糖,然后进行磁共振成像。果糖增加了小肠含水量,菊糖增加患者和对照者的结肠容量和气体,但是仅患者出现肠道症状。这突出显示了在健康人和IBS患者中可发酵碳水化合物产生类似的生理反应,提示IBS症状的发病机制是对产气的内脏超敏反应升高,而不是过量的气体产生本身。

除了减少小肠含水量和结肠气体外,来自临床试验的许多初步观察结果提示了低FODMAP饮食的其他潜在作用机制。在之前提到的两项随机对照试验中,低FODMAP饮食导致尿组胺减少8倍,促炎IL-6和IL-8减少,提示低FODMAP饮食可调节免疫活化。

低FODMAP饮食除改善肠道症状外,它对肠道微生物群也产生深远的影响。最近的研究证实了先前的发现,低FODMAPs的饮食低导致双歧杆菌浓度降低,罗斯氏菌和瘤胃球菌浓度升高。然而,肠腔微环境的这种变化与肠道症状变化之间的联系仍然不清楚。

低FODMAP饮食是一种复杂、昂贵和负担重的饮食,因此在预测饮食应答方面将会有重大的进展。一项对584名功能性肠病患者的研究显示,果糖刺激导致的慢性腹泻和甲烷浓度呼吸峰值能够正向预测低FODMAP饮食缓解果糖不耐受患者的症状(OR 2.62,P=0.07;OR 1.53,P=0.042),而慢性恶心负向预测症状缓解(OR 0.33,P=0.002)。此外,瑞典的一项研究显示对低FODMAP饮食应答的IBS患者的肠道细菌谱与无应答者基线不同,特别是在干预前后,无应答者的细菌丰度高于应答者,无应答者在基线时的“生态失调指数”得分高于应答者。需要更多的研究,直到可以用于选择哪些患者在临床实践中最有可能响应低FODMAP饮食。

▌无麸质饮食

IBS患者的胃肠道症状与包括小麦、大麦和黑麦在内的膳食麸质之间存在明确的,有据可查的关联,引起人们对无麸质饮食(GFD)管理IBS的兴趣。最近在猜测非腹部麸质/小麦过敏的IBS患者中有两项随机双盲安慰剂对照试验,研究重新引入麸质后的情况,参与者接受三/四周GFD,重新摄入麸质后分别有55/77(71%)和65/164(40%)人出现症状反应(使用不同的胃肠症状问卷)。

Ellis等人进行了一项七天交叉试验研究重新摄入麸质胶囊后的情况,在完成试验的那些人中,18/53(34%)在摄入麸质后症状恶化。但摄入安慰剂也在很多人中引起症状,表明真正由麸质引起的效应可能比观察到的要少得多。Zanwar等人的重摄入研究显示,小麦面包引起的症状(阳性,55.7%)较非麸质面包(安慰剂,33.3%,P<0.05)更为严重。

尽管有这些支持性的研究结果,但在任何一项研究中都无法确认麸质过敏,因为在给予阳性刺激时可能有其他的潜在的作用物,例如,小麦面包中含几个与胃肠症状相关连的其他成分如淀粉酶胰蛋白酶抑制剂和果聚糖,Ellis等人使用的麸质胶囊中含有其他非麸质蛋白质,因而无法测定麸质的单独效应。

我们还必须承认,GFD不仅可能带来经济负担,而且会导致营养不良的风险增加。事实上,最近在11万多名没有腹腔疾病的人群中进行的流行病学研究发现,麸质摄入量最低的人群冠心病发病率较高,这是由于他们的全谷物摄入量较低。

总之,对小麦过敏可能会影响IBS亚组,但鉴定具体的小麦组分(果聚糖、麸质、淀粉酶-胰蛋白酶抑制剂),敏感程度以及是否需要短暂或终身排除需要进一步研究。

▌补充和替代医学

常规疗法治疗IBS症状的功效多变,使一些患者和临床医生的注意力移向补充替代医学(CAM)。CAMs包括了广泛的治疗方法,尽管很少有人在可靠的临床试验中进行测试。

在IBS中,CAM的最有说服力的应用证据是薄荷油及其有效成分薄荷醇。薄荷油的益处主要归功于其抗痉挛特性,尽管它与其他几种作用包括抗感染和抗炎有关。荟萃分析的综述表明,与安慰剂相比,薄荷油的总体减轻IBS症状(RR 2.23,95%CI,1.78-2.81),改善腹痛(RR 2.14,95%CI,1.64-2.79)。尽管如此,研究的总体质量仅在低分级临床指南建议中得到肯定。

最近,一项为期4周的随机双盲安慰剂对照试验显示食用薄荷油后总体IBS症状评分减少40%,安慰剂组为24%(P=0.03)。虽然有利用前景,但是这些结果普遍性局限于没有服用普通药物和补品的特定人群。

也有越来越多的证据支持组合CAM。最近的随机对照试验报道,与安慰剂相比,食用姜黄素和茴香油后IBS症状严重程度降低更多(平均相对:50.1±28.9%vs.26.1±30.6%,P<0.001)。在来自不同姜黄属植物、鱼油、薄荷油、香芹籽油的姜黄素类化合物和精油的专属混合物同维生素B1,B9和D3之间也有类似的现象(点变化:-113.0±64.9 vs-38.7±64.5,P<0.001)。

虽然这些研究与美国食品和药物管理局批准所需要的更为严格设计的试验相比规模较小,且持续时间较短,但CAM在IBS中的作用值得引起更多高质量临床试验的重视。

▌未来的方向和结论

对IBS病理生理学的日益了解支持了各种饮食疗法的机械性潜力,尽管这些疗法主要集中于治疗症状而不是治疗潜在的病因。虽然如此,IBS是一种异质性的疾病已变得越来越清楚,因此一种营养疗法不可能有益于所有人。目前IBS症状管理的最令人信服的证据是车前草纤维、益生菌和低FODMAP饮食,虽然这些疗法的效果强弱不等。为了促进IBS的饮食管理,研究需要调查营养在IBS潜在病因方面的作用。考虑到肠道微生物群在IBS发病机制中的作用以及饮食为其关键性的影响因素,肠道微生物群似乎是一个有吸引力的目标。

原始出处:
Eirini Dimidi, Megan Rossi, and Kevin Whelan. Irritable bowel syndrome and diet: where are we in 2018? Curr Opin Clin Nutr Metab Care. 2017, 20:456–463.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1896273, encodeId=497a18962e386, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Thu Jun 21 17:51:00 CST 2018, time=2018-06-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1887836, encodeId=20bd188e836bf, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Tue Jul 03 19:51:00 CST 2018, time=2018-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290399, encodeId=38ef2903993f, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Sat Feb 24 07:06:24 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289863, encodeId=63dd2898636d, content=肠易激综合征和饮食., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Thu Feb 22 07:24:12 CST 2018, time=2018-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289582, encodeId=cb0e289582f5, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/01/15/8213228fe923915543544ad3da7e1c64.jpg, createdBy=6bd82014262, createdName=秀红, createdTime=Wed Feb 21 06:17:24 CST 2018, time=2018-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289578, encodeId=021f2895e859, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Wed Feb 21 06:11:55 CST 2018, time=2018-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431128, encodeId=758a14311284b, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Mon Feb 19 00:51:00 CST 2018, time=2018-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288967, encodeId=0d8b28896e10, content=谢谢.祝梅斯医学越来越好!, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sun Feb 18 18:31:29 CST 2018, time=2018-02-18, status=1, ipAttribution=)]
    2018-06-21 一闲
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    2018-07-03 guojianrong
  3. [GetPortalCommentsPageByObjectIdResponse(id=1896273, encodeId=497a18962e386, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Thu Jun 21 17:51:00 CST 2018, time=2018-06-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1887836, encodeId=20bd188e836bf, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Tue Jul 03 19:51:00 CST 2018, time=2018-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290399, encodeId=38ef2903993f, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Sat Feb 24 07:06:24 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289863, encodeId=63dd2898636d, content=肠易激综合征和饮食., beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Thu Feb 22 07:24:12 CST 2018, time=2018-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289582, encodeId=cb0e289582f5, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/01/15/8213228fe923915543544ad3da7e1c64.jpg, createdBy=6bd82014262, createdName=秀红, createdTime=Wed Feb 21 06:17:24 CST 2018, time=2018-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=289578, encodeId=021f2895e859, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f22260741, createdName=121832a9m88暂无昵称, createdTime=Wed Feb 21 06:11:55 CST 2018, time=2018-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431128, encodeId=758a14311284b, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Mon Feb 19 00:51:00 CST 2018, time=2018-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288967, encodeId=0d8b28896e10, content=谢谢.祝梅斯医学越来越好!, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sun Feb 18 18:31:29 CST 2018, time=2018-02-18, status=1, ipAttribution=)]
    2018-02-24 1209e435m98(暂无昵称)

    学习了.谢谢分享

    0

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    2018-02-22 jyzxjiangqin

    肠易激综合征和饮食.

    0

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    2018-02-21 秀红

    学习了

    0

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    2018-02-21 121832a9m88暂无昵称

    学习了

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    2018-02-18 虈亣靌

    谢谢.祝梅斯医学越来越好!

    0

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