替考拉宁在中国成人患者中的群体药动学研究

目的建立中国成年患者的替考拉宁(teicoplanin,TEC)群体药动学(population pharmacokinetics,PPK)模型,考察TEC药动学参数的影响因素。方法前瞻性收集139例革兰阳性球菌感染患者静脉注射TEC后的222份常规监测血药浓度和相关信息,采用一级消除的一室模型进行数据拟合,并应用非线性混合效应模型(nonlinear mixed effect model,NONMEM)程序建立PPK模型。采用Bootstrap、正态预测分布误差法(normalized predictive distribution error,NPDE)进行最终模型评价。利用蒙特卡洛模拟法对给药方案进行优化。结果确定了肌酐清除率(creatinine clearance,CLcr)、白蛋白(albumin,ALB)为影响TEC清除率的主要因素。最终模型为:CL(L·h^-1)=1.24×(CLcr/77)0.564×31/ALB;V(L)=69.2。验证表明,模型稳定、有效,且有较好的预测效能。对于不同ALB和CLcr的多数患者起始负荷剂量400 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案可达有效治疗谷浓度。严重感染者需调整负荷剂量至800 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案来确保血药浓度达到15 mg·L^-1以上。结论本实验报道了CLcr、ALB对TEC清除率有显著影响,所建模型对TEC在中国成人患者中实现个体化给药具有重要应用价值。     

Bone Metabolism Discrepancy in Type 2 Diabetes Mellitus Patients With and Without Non-Alcoholic Fatty Liver Disease

To explore the distribution of several bone metabolic indicators in type 2 diabetes patients (T2DM) with and without non-alcoholic fatty liver disease (NAFLD) and to preliminarily evaluate the relationship of bone metabolism with NAFLD in patients with T2DM. The hospitalized patients with T2DM were divided into the group of T2DM complicated with NAFLD and the group of T2DM alone according to the results of ultrasonic diagnosis. The general information and laboratory test data such as bone metabolism indexes of these patients were collected and the differences of the indexes between the 2 groups were compared. Furthermore, the independent influencing factors of NAFLD in patients with T2DM were analyzed. A total of 186 patients were included in the study. Compared with patients with T2DM only, patients with T2DM combined with NAFLD were characterized with younger age (p < 0.001), higher BMI (p = 0.016), ALT (p = 0.001), TG (p = 0.005), HOMA-IR (p = 0.005), and lower HDL-C (p = 0.031). Significant discrepancy of age (OR 1.052, p = 0.001), ALT (OR 0.964, p = 0.047), HOMA-IR (OR 0.801, p = 0.005), and T-PINP (OR 1.022, p = 0.008) was found using multivariate logistic regression model. Significant discrepancy of T-PINP was found in T2DM patients with and without NAFLD. Further studies are needed to explore whether T-PINP could be used as a predictor of fatty liver disease, osteoporosis, and other related complications in patients with T2DM.     

The impact of circumferential tumour location on the clinical outcome of rectal cancer patients managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision

AimTo investigate the impact of circumferential tumour location on neoadjuvant chemoradiotherapy (CRT) response and its prognostic value for locally advanced rectal cancer (LARC) patients after CRT and surgery.MethodsA retrospective study was performed on 486 patients with LARC who received neoadjuvant CRT and surgical treatment. The rate of pathological complete response (pCR) and survival among patients with anteriorly, laterally, and posteriorly located tumours were compared. Logistic regression was performed to identify pCR predictors.ResultsThe anterior tumours exhibited the highest pCR rate of 26.7%, which was slightly higher than the 20.0% and 12.3% for lateral and posterior tumours, respectively (P = 0.006). The 5-year Overall survival (OS) rates after CRT were similar among the anterior, lateral, and posterior groups (anterior vs lateral vs posterior: 81.1% vs 89.9% vs 84.1%, P = 0.6368). Multivariate analysis revealed that the circumferential tumour location, post-CRT serum CEA and post-CRT tumour thickness measured by MRI were independently correlated with achieving pCR.ConclusionThis study is the first, to the best of our knowledge, to show that anterior LARC exhibited the highest pCR rate after neoadjuvant CRT. Patients with anterior rectal cancers do not have different prognoses from those with non-anterior cancers if they undergo neoadjuvant CRT.     

Changes in Bone Marrow Adipose Tissue in Transgender and Gender Non-Conforming Youth Undergoing Pubertal Suppression: A Pilot Study

Pubertal suppression with gonadotropin-releasing hormone (GnRH) agonists in transgender and gender non-conforming (TGNC) youth may affect acquisition of peak bone mass. Bone marrow adipose tissue (BMAT) has an inverse relationship with bone mineral density (BMD). To evaluate the effect of pubertal suppression on BMAT, in this pilot study we prospectively studied TGNC youth undergoing pubertal suppression and cisgender control participants with similar pubertal status over a 12-month period. BMD was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Magnetic Resonance T1 relaxometry (T1-R) and spectroscopy (MRS) were performed to quantify BMAT at the distal femur. We compared the change in BMD, T1-R values, and MRS lipid indices between the two groups. Six TGNC (two assigned female and four assigned male at birth) and three female control participants (mean age 10.9 and 11.7 years, respectively) were enrolled. The mean lumbar spine BMD Z-score declined by 0.29 in the TGNC group, but increased by 0.48 in controls (between-group difference 0.77, 95% CI: 0.05, 1.45). Similar findings were observed with the change in trabecular volumetric BMD at the 3% tibia site (-4.1% in TGNC, +3.2% in controls, between-group difference 7.3%, 95% CI: 0.5%-14%). Distal femur T1 values declined (indicative of increased BMAT) by 7.9% in the TGNC group, but increased by 2.1% in controls (between-group difference 10%, 95% CI: -12.7%, 32.6%). Marrow lipid fraction by MRS increased by 8.4% in the TGNC group, but declined by 0.1% in controls (between-group difference 8.5%, 95% CI: -50.2%, 33.0%). In conclusion, we observed lower bone mass acquisition and greater increases in BMAT indices by MRI and MRS in TGNC youth after 12 months of GnRH agonists compared with control participants. Early changes in BMAT may underlie an alteration in bone mass acquisition with pubertal suppression, including alterations in mesenchymal stem cells within marrow.     

胰淀素及肾上腺髓质素与骨代谢关系的研究进展

胰淀素及肾上腺髓质素属于降钙素/降钙素基因相关肽家族成员,有相似的二级结构,均可促进骨合成代谢。分子生物学研究显示,降钙素受体、降钙素受体样受体及受体活性调节蛋白等相关分子可能是它们的受体,而蛋白激酶A、蛋白激酶C及细胞外信号调节激酶与其胞内信号转导有关。临床研究发现血浆胰淀素水平在骨质疏松患者体内下降。作为新发现的骨代谢调节因子,它们将成为治疗代谢性骨病的一类新型药物。     

压力调节容量控制通气对肺损伤犬血流动力学、呼吸力学和呼吸功能的影响

目的 探讨压力调节容量控制(PRVC)通气模式对健康及急性肺损伤(ALI)模型犬的血流动力学、呼吸力学和呼吸功能的影响。方法 PRVC和间歇正压通气(IPPV)两种通气模式在呼气末压为0、0．5、1．0和1．5kPa时，分别测定健康犬及油酸诱发ALI犬的血流动力学、呼吸力学及血气参数。结果 健康犬PRVC较IPPV模式下除了在PEEP为0．5kPa时，气道峰压(PIP)、肺动态顺应性(Cdyn)和肺血管阻力(PVR)的影响差异有显著性，对血流动力学、呼吸力学及呼吸功能的影响差异均无显著性。ALI犬PRVC较IPPV模式下各PEEP水平的PIP、平均气道压(mPaw)、Cdyn、动脉血氧分压[pa(O2)]和氧耗(VO2)的影响均有显著意义，但两种通气模式对血流动力学的影响差异无显著性。结论 与IPPV相比，PRVC通气模式能降低PIP，增加Cdyn和提高pa(O2)，两模式对血流动力学的影响差异无显著性，PRVC更适用于ALI／ARDS的治疗。     

肱动脉血流动力学和掌温检测在胸交感神经干切断术中的临床意义

目的探讨超声检测肱动脉血流动力学变化和手掌测温在胸交感神经干切断术治疗手汗症的应用价值。方法对150例手汗症病人分别于胸交感神经干切断术前与术后测量手掌皮温,并对其中33例行双侧肱动脉超声血流动力学指标检测。结果全组术后平均掌温升高(2·8±1·0)℃,其中125例平均掌温显著升高(3·24±0·20)℃,25例升高不显著,仅(0·64±0·10)℃。术毕超声检测肱动脉血管内径增大,血流量显著增多,收缩期峰值与舒张期终末值均变大,搏动指数变小,收缩期/舒张期比值显著变小,行配对t检验显示,以上参数P值均<0·05,差异有统计学意义。结论术中超声检测肱动脉血流动力学变化,结合掌温测量是判断胸交感神经干切断成功的有效方法。