A Clinical Study of Vonoprazan Fumarate Tablets for the Treatment of Non-erosive Reflux Disease
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摘要:
目的 研究富马酸伏诺拉生片与艾司奥美拉唑镁肠溶片在治疗非糜烂性反流病(non-erosive reflux disease,NERD)中的效果及不良反应对比。 方法 选取124例NERD患者,采用随机数字表法分为观察组62例和对照组62例。观察组给予富马酸伏诺拉生片,对照组给予艾司奥美拉唑镁肠溶片,疗程均为4周。对幽门螺旋杆菌(helicobacter pylori,HP)阳性的患者进一步根除HP。比较2组患者的临床疗效、反流性疾病问卷量表(reflux disease questionnaire,RDQ)评分、匹兹堡睡眠质量指数(pittsburgh sleep quality index,PSQI) 评分、治疗前后食管pH值变化、HP根除率及不良反应发生率。 结果 观察组总有效率高于对照组(P < 0.05),观察组治疗后RDQ评分低于对照组(P < 0.05),观察组治疗后PSQI评分低于对照组(P < 0.05),观察组治疗后pH < 4反流次数、> 5 min反流次数和pH < 4总时间低于对照组(P < 0.05),观察组HP根除率高于对照组(P < 0.05)。观察组和对照组比较,总不良反应率无明显差异(P > 0.05)。 结论 在治疗非糜烂性反流病方面,富马酸伏诺拉生片与艾司奥美拉唑镁肠溶片对比,疗效显著,可改善睡眠质量,抑酸更强,提高HP根除率,并不增加不良反应。 -
关键词:
- 富马酸伏诺拉生片 /
- 艾司奥美拉唑镁肠溶片 /
- 非糜烂性反流病
Abstract:Objective To study the efficacy and adverse reactions of vonoprazan fumarate tablets and esomeprazole magnesium enteric-coated tablets in the treatment of non-erosive reflux disease(NERD). Methods A total of 124 patients with NERD were selected and divided into treatment group(62 cases) and control group(62 cases) by random number table method. Treatment group received vohoprazan fumarate tablet, while control group received esomeprazole magnesium enteric-coated tablet, and the course of treatment was 4 weeks. HP was eradicated in helicobacter pylori(HP)-positive patients. The clinical efficacy, reflux disease questionnaire(RDQ )score, pittsburgh sleep quality index score, changes of esophageal pH before and after treatment、HP eradication rate and incidence of adverse reactions were compared between the two groups. Results The treatment group showed a higher overall effectiveness compared to the control group(P < 0.05). After treatment, the RDQ scores in the treatment group were lower than those in the control group(P < 0.05). Similarly, the PSQI scores in the treatment group were lower than those in the control group(P < 0.05). Additionally, the treatment group exhibited fewer reflux episodes with pH < 4, reflux episodes lasting > 5 minutes, and a lower total time with pH < 4 compared to the control group(P < 0.05). The eradication rate of HP in the treatment group was higher than that in the control group(P < 0.05). There was no significant difference in the overall rate of adverse reactions between the treatment group and the control group(P > 0.05). Conclusion In the treatment of non-erosive reflux disease, compared to esomeprazole magnesium enteric-coated tablets, vonoprazan fumarate tablets show significant efficacy, improve sleep quality, provide stronger acid suppression, increase the eradication rate of Helicobacter pylori(HP), and do not increase adverse reactions. -
多囊卵巢综合征( polycystic ovary syndrome,PCOS)与慢性低度炎症反应相关,炎症状态影响PCOS的发病及发展的观点越来越受到重视[1],69.7%起病于青春期,所以对PCOS的诊断应从青春期开始,但青春期的生理特点与PCOS症状和体征重叠,致使青春期PCOS不能及时发现,因此,2018年多囊卵巢综合征中国诊疗指南中提出了疑似PCOS的诊断标准[2] :月经稀发或闭经或不规则子宫出血(即稀发排卵或无排卵,OA))是诊断的必需条件。另外再符合下列2项中的1项:(1)高雄激素临床表现或高雄激素血症(hyperandrogenism,HA);(2)超声下表现为PCOM。对于疑似PCOS患者是否需要过早干预?干预的指征是什么?目前缺乏统一的共识。白介素-6(Interleukin 6,IL-6)、C反应蛋白(C-reactive protein,CRP)及肿瘤坏死因子-α(TNF-α)与PCOS密切相关[3],但是其在青春期PCOS中的作用与相关性,目前国内研究甚少,本文通过检测疑似PCOS青春期患者、青春期PCOS患者及正常青春期女性血清IL-6、CRP及TNF-α的水平,了解其临床表达特点,为早期识别、早期干预青春期PCOS提供临床依据,现报道如下。
1. 资料与方法
1.1 一般资料
选取 2020年8月至2021年11月昆明市妇幼保健院就诊的80例符合疑似PCOS诊断标准的青春期女性患者作为研究对象(即疑似PCOS组),60 例青春期PCOS患者作为PCOS组,同期50例正常青春期女性作为对照组。根据疑似PCOS临床特征,将80例疑似PCOS分为2个亚组:OA+HA组(40例);OA+PCOM组(40例)。 本研究通过昆明市妇幼保健院伦理委员会批准。纳入标准符合2018年多囊卵巢综合征中国诊疗指南中疑似PCOS诊断标准[4]。
1.2 检测指标及检测方法
所有受试者在月经周期(自然周期或黄体酮撤退出血)第2~4天或闭经期(B超下无优势卵泡),清晨(8:00~10:00)空腹(禁食8~12h)抽取肘静脉血,检测血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)、雌激素(E2)、泌乳素(PRL)。采用用酶联免疫吸附试验测定血清CRP和TNF-α,采用化学发光法检测血清IL-6的浓度。分别比较疑似PCOS组与对照组,疑似PCOS组与PCOS组患者血清IL-6、CRP及TNF-α的水平,分析血清IL-6、CRP及TNF-α在疑似PCOS青春期女性中的表达特点;比较疑似PCSO组OA+HA组与OA+PCOM患者血清IL-6、CRP及TNF-α的水平,分析不同亚组血清IL-6、CRP及TNF-α的表达特点。
1.3 统计学处理
采用SPSS22.0软件进行数据分析,计数资料用例数和百分比(%)表示,组间比较采用χ2检验,计量资料采用(
$\bar x \pm s $ )表示,组间比较采用 t 检验;P<0.05为差异具有统计学意义。2. 结果
2.1 各组间一般资料比较
疑似PCOS组与对照组、疑似PCOS组与PCOS组年龄、初潮年龄及体质数(BMI)比较差异均无统计学意义,具有可比性(P > 0.05),见表1~2。
表 1 疑似PCOS组与对照组一般资料比较($\bar x \pm s $ )Table 1. Comparison of general information between Suspected Adolescence PCOS group and the control group ($\bar x \pm s $ )组别 n 年龄(岁) 初潮年龄(岁) BMI(kg/m2) 对照组 50 16.32 ± 1.96 12.87 ± 1.08 20.56 ± 2.93 疑似PCOS组 80 16.08 ± 2.33 12.63 ± 0.88 21.33 ± 2.55 t 0.606 1.385 −1.581 P 0.545 0.169 0.116 表 2 疑似PCOS组与PCOS组一般资料比较($\bar x \pm s $ )Table 2. Comparison of general information between Suspected Adolescence PCOS group and PCOS group ($\bar x \pm s $ )组别 n 年龄(岁) 初潮年龄(岁) BMI(kg/m2) 对照组 50 16.32 ± 1.96 12.87 ± 1.08 20.56 ± 2.93 疑似PCOS组 80 16.08 ± 2.33 12.63 ± 0.88 21.33 ± 2.55 t 0.780 −0.352 0.354 P 0.437 0.726 0.724 2.2 各组间血清IL-6、CRP及TNF-α水平比较
疑似PCOS组患者血清CRP值、IL-6值明显高于对照组,差异具有统计学意义(P < 0.05),见表3;疑似PCOS组患者血清TNF-α、CRP值明显低于PCOS组,差异具有统计学意义(P < 0.05),见表4。
表 3 疑似PCOS组与对照组血清IL-6、CRP及TNF-α水平比较($\bar x \pm s $ )Table 3. Comparison of the levels of IL-6、CRP、TNF-a between Suspected Adolescence PCOS group and the control group ($\bar x \pm s $ )组别 n CRP(mg/L) TNF-α(pg/mL) IL-6(pg/mL) 对照组 50 3.48 ± 0.59 0.99 ± 0.33 7.03 ± 1.38 疑似PCOS组 80 8.91 ± 0.81 0.95 ± 0.78 22.53 ± 1.93 t −41.057 0.344 −49.410 P 0.000* 0.732 0.000* *P < 0.05。 表 4 疑似PCOS组与PCOS组血清IL-6、CRP及TNF-α水平比较($\bar x \pm s $ )Table 4. Comparison of the levels of IL-6、CRP、TNF-a between Suspected Adolescence PCOS group and PCOS group ($\bar x \pm s $ )组别 n CRP(mg/L) TNF-α(pg/mL) IL-6(pg/mL) PCOS组 60 9.32 ± 0.95 1.93 ± 0.49 22.05 ± 2.77 疑似PCOS组 80 8.91 ± 0.81 0.95 ± 0.78 22.53 ± 1.93 t 2.751 7.951 0.326 P 0.000* 0.000* 0.801 *P < 0.05。 2.3 OA+HA组与OA+PCOM组炎症因子水平比较
OA+HA组患者血清CRP值、TNF-α值及IL-6值明显高于OA+PCOM组,差异具有统计学意义(P < 0.05),见表5。
表 5 OA+HA组与OA+PCOM组炎症因子水平比较($\bar x \pm s $ )Table 5. Comparison of the levels of inflammatory factors between OA+PCOM Group and OA+HA group ($\bar x \pm s $ )组别 n CRP(mg/L) TNF-α(pg/mL) IL-6(pg/mL) OA+HA组 40 9.12 ± 1.08 0.99 ± 0.27 23.90 ± 4.08 OA+PCOM组 40 4.01 ± 0.52 0.78 ± 0.42 15.71 ± 2.92 t 26.962 2.660 10.324 P 0.000* 0.009* 0.006* *P < 0.05。 3. 讨论
3.1 青春期多囊卵巢综合征的认识
2018年PCOS中国诊疗指南未颁布前,临床一直沿用2003年鹿特丹PCOS诊断标准[5],在一项关于青春期门诊妇科疾病患病情况的调查中显示,根据鹿特丹诊断标准,青春期PCOS的患病率仅次于青春期功血及意外妊娠。临床医生对青春期PCOS过度诊断、过度治疗的现象,对患者及家属造成了不良的影响和心理负担。需尽快发现用于识别早期PCOS的指标。现已被证实PCOS与慢性低度炎症反应有关,特别是IL-6、CRP及TNF-α与PCOS密切相关。笔者前期的研究结果也提示,青春期PCOS患者血清CRP、TNF-α、IL-6水平明显升高,说明炎症因子可能参与青春期PCOS的发病过程。
3.2 炎症因子与青春期PCOS的相关性分析
有研究结果显示,CRP是PCOS慢性低度炎症中对可靠的指标,并且高水平CRP也可能为PCOS的固有特征[6-7], IL-6为判定慢性炎症反应的一项常用临床指标,国内外大量研究表明,高水平的IL-6与PCOS的发病过程密切相关。此外,IL-6通过刺激肝细胞合成分泌CRP,说明IL-6通过多条途径对PCOS产生影响[8]。但也有研究显示,CRP、IL-6 的水平取决于肥胖程度,与 PCOS 疾病无关[9-10]。童凤梅等[11]的研究结果显示,CRP与雄激素水平表达呈正相关。本研究结果显示,疑似PCOS组患者血清CRP值、IL-6值明显高于正常对照组(P < 0.05),与PCOS组比较差异无统计学意义(P < 0.05),提示血清CRP、IL-6水平增高可能成为启动早期干预疑似青春期PCOS的指标。早在2010年,就有专家对TNF-a与PCOS的关系进行研究,近几年,越来越多的研究显示PCOS患者血清TNF-α的水平高于正常人,且随着胰岛素抵抗程度的增高,血清TNF-α水平也呈现增高趋势,TNF-α还通过影响性激素结合球蛋白,增加游离睾酮含量[12-13]。国外有研究表明,TNF -α与睾酮水平呈正相关性[14],国内2021年最新的一项关于TNF-α基因多态性与PCOS的相关性的文章,得出的结果显示[15],TNF-α基因遗传变异与 PCOS 的发生具有相关性,这对于PCOS的诊治具有重要意义,也说明了TNF-α可能参与了PCOS的发病过程,并发挥着重要作用。本研究结果显示,疑似PCOS组的TNF-α水平明显低于PCOS组(P < 0.05),与正常对照组无明显差异(P > 0.05),但OA+HA组TNF-α水平明显高于OA+PCOM组(P < 0.05),说明了TNF-α水平与睾酮水平呈正相关性。
综上所述,炎症因子IL-6、CRP作为慢性炎症的重要血清标志物,可能参与青春期PCOS的发病过程,在疑似PCOS青春期患者中具有高水平的表达,为疑似PCOS患者的早期干预提供依据,建议在疑似PCOS患者中进行2种标志物的筛查,以协助早期识别青春期PCOS。
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表 1 观察组和对照组一般资料比较[$\bar x \pm s$/n(%)]
Table 1. Comparison of general data between treatment group and control group[$ \bar x \pm s $/n(%)]
组别 性别
(男/女)年龄
(岁)BMI
(kg/m2)吸烟 饮酒 HP感染 观察组 27/35 57.74±12.81 23.86±2.58 10(16.13) 12(19.35) 34(54.84) 对照组 24/38 56.79±11.29 23.12±2.27 9(14.52) 13(20.97) 32(51.61) t/χ2 0.300 0.439 1.689 0.062 0.050 0.130 P 0.584 0.662 0.094 0.803 0.823 0.719 表 2 2组患者治疗后临床疗效[n(%)]
Table 2. Clinical efficacy of two groups of patients after treatment [n(%)]
组别 n 显效 有效 无效 总有效率 观察组 62 34(54.84) 24(38.71) 4(6.45) 58(93.55) 对照组 62 29(46.77) 18(29.03) 15(24.19) 47(75.81) χ2 / / / / 7.521 P / / / / 0.006* *P < 0.05。 表 3 2组患者治疗前后RDQ评分[($\bar x \pm s$),分]
Table 3. RDQ scores before and after treatment in the two groups [($\bar x \pm s$),points]
组别 n 治疗前 治疗后 观察组 62 17.13±6.11 9.03±3.28 对照组 62 16.81±5.59 10.48±2.86 t / 0.307 −2.624 P / 0.760 0.010* *P < 0.05。 表 4 2组患者治疗前后PSQI评分[($\bar x \pm s$),分]
Table 4. PSQI score before and after treatment in the two groups [($\bar x \pm s$),points]
组别 n 治疗前 治疗后 观察组 62 7.90±2.51 4.76±1.89 对照组 62 7.85±1.57 5.95±1.74 t / 0.129 −3.660 P / 0.898 < 0.001* *P < 0.05。 表 5 2组患者治疗前后食管pH检测变化($\bar x \pm s$)
Table 5. The changes of esophageal pH before and after treatment in the two groups of patients($\bar x \pm s$)
组别 n pH < 4反流次数(次) > 5 min反流次数(次) pH < 4总时间(min) 治疗前 治疗后 治疗前 治疗后 治疗前 治疗后 观察组 62 28.37±8.71 11.16±2.57 5.76±2.41 1.69±0.86 74.84±12.30 16.81±5.02 对照组 62 28.05±8.15 13.02±5.36 5.42±2.27 2.87±1.15 71.77±11.23 23.97±6.17 t / −0.213 2.457 0.804 −6.447 1.449 −7.115 P / 0.832 0.015 0.423 < 0.001* 0.150 < 0.001* *P < 0.05。 表 6 2组患者HP感染者根除率(%)
Table 6. The eradication rate of HP infection in the two groups of patients (%)
组别 n 根除率(%) 根除前HP阳性 根除后HP阴性 观察组 34 31 31/34(91.2) 对照组 32 20 20/32(62.5) χ2 / / 4.030 P / / 0.045* *P < 0.05。 -
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