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目的 通过UHPLC-Q-TOF-MS代谢组学探讨艾灸关元穴对老年大鼠肾代谢物的影响,进而为艾灸关元穴的作用机制提供参考。方法 将8月龄SD雄性大鼠设为成年对照组(8只),21月龄SD雄性大鼠随机分为老年对照组(8只)、老年金匮肾气丸组(7只)、老年艾灸组(8只)。老年金匮肾气丸组每日按体重给药,老年艾灸组每日艾灸关元穴15 min,均每周5天。实验持续13周后检测大鼠肾组织线粒体呼吸耗氧速率、琥珀酸脱氢酶(SDH)活性以及血清肾功能指标,观察肾脏病理变化,结合UHPLC-Q-TOF-MS技术对大鼠的肾组织进行代谢轮廓分析,筛选代谢差异物并进行鉴定。结果 与老年对照组比较,老年艾灸组大鼠肾线粒体的呼吸耗氧速率和SDH酶的活力显著提高(P<0.01)。代谢组学结果显示,肾组织中筛选出13个共同差异化合物,分别是丁酸十二烷基酯、亚油酰胺、5-甲基四氢叶酸、PC(16∶0/22∶5(7Z,10Z,13Z,16Z,19Z))、6,8-二羟基嘌呤、1,2,3-丙烷三羧酸、3-(4-甲氧基苯基)-2-氧代丙酸、吲哚-3-乙酰甘氨酸、亚麻油酸、9,10-环氧十八烷酸、二十二碳五烯酸(22n-6)、牛磺胆酸、LysoPS (18∶0/0∶0)。结论 艾灸关元穴可通过调控老年大鼠的牛磺酸和亚牛磺酸代谢、α-亚麻酸代谢、亚油酸代谢、甘油磷脂代谢来调节肾的能量代谢。  相似文献   
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Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

Methods

A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves.

Results

Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention.

Conclusions

In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler.  相似文献   
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Background

Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact.

Objective

We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER).

Study Design

Retrospective analysis of pharmaceutical sales data.

Methods

From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed “unmanaged uptake,” and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market).

Results

Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The “unmanaged uptake” assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data.

Conclusions

This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results.  相似文献   
148.
We report a case of disseminated Trichosporon asahii in a patient on systemic antifungal therapy who presented with multiple cutaneous nodules suggestive of fungal infection. Histologic features resembled neutrophilic eccrine hidradenitis but staining with periodic acid‐Schiff and Gomori methenamine silver confirmed the clinical diagnosis. This case highlights the importance of maintaining suspicion for trichosporonosis and contextualizing histologic findings within the underlying clinical picture.  相似文献   
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Shaving and other modes of epilation can cause undue anxiety, pain, or skin irritation in children. Here, we present hair trimming as a safe, painless, and cost‐effective alternative for patients with unwanted hair which may be performed indefinitely or until the child is old enough to direct management. In select cases, removing unwanted hair using this technique may facilitate dermatologic surveillance.  相似文献   
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