血清骨唾液酸蛋白的生物变异性研究

目的　骨唾液酸蛋白（Ｂｏｎｅ ｓｉａｌｏｐｒｏｔｅｉｎ,简称ＢＳＰ）是由成骨细胞分泌的一种非胶原蛋白质,反映骨转换和骨形成的指标。最近研究认为：血清ＢＳＰ浓度可反映破骨细胞活性和骨吸收过程,也可能是一个骨吸收指标。本实验测定了血清ＢＳＰ在人体内的生物变异性。方法　采用ＲＩＡ 法测定了２９０例不同性别和年龄的正常人血清ＢＳＰ的正常值,血清ＢＳＰ的天－天变异性及２４ ｈ 生物周期。　结果　在儿童组血清ＢＳＰ正常水平明显高于成人组,其最高值在新生儿期和青春期。绝经后妇女其血清浓度比绝经前妇女水平明显升高（Ｐ＜ ０．０５）。血清ＢＳＰ在每天同一时间的波动范围在 ７．３％ 至１７．７％ （平均１１．７％ ）。２４ ｈ 内有一个明显的生物周期性变化,表现为峰值在凌晨４～８ 时,然后逐渐下降直到午后１４时为最低。其生物周期的最大波幅为±２０％ ,（平均血浓度为１０．５ ｎｇ／ｍ ｌ）。结论　血清ＢＳＰ反映了骨转换的生理变化与年龄有明显相关性,其血清水平２４ ｈ 内有一个明显的生物周期,而天与天之间变异性较小。     

Manubriosternal subluxation/dislocation can lead to manubriosternal septic arthritis in patients with kyphoscoliosis

Locally deranged joint anatomy can predispose to septic arthritis which can be managed by surgical debridement. We present a case of manubriosternal subluxation/dislocation caused by kyphoscoliosis leading to manubriosternal septic arthritis.     

Long‐term effects of rapid weight gain in children,adolescents and young adults with appropriate birth weight for gestational age: the kiel obesity prevention study

Aim: This study investigates the effect of rapid weight gain in term children, adolescents and young adults born appropriate for gestational age. Methods: In all, 173 girls and 178 boys aged 6.1–19.9 (12.5 ± 3.1)years participated. Rapid weight gain (group 1) was defined as a change in weight‐SDS (standard deviation score) from birth till two years >0.67, ‘no change’ as ≥?0.67 and ≤0.67 (group 2) vs ‘slow weight gain’ as 90th age‐/sex‐specific BMI‐percentile was defined as overweight. Parental BMI, socio‐economic status and lifestyle were assessed as confounders. Results: A total of 22.8% gained weight rapidly, and 15.7% was overweight. Group 1 compared with group 2 and 3 subjects was taller, heavier and had a higher prevalence of overweight (girls/boys: 26.2%/28.9% vs 11.6%/19.0% vs 2.8%/5.0%; p < 0.01/p < 0.05). Concomitantly, a higher WC, %FM and FFM were observed. Rapid weight gain was positively associated with REE (adjusted for FFM) in boys (r = 0.26; p < 0.01), but not with cardio‐metabolic risk factors. Conclusion: Rapid weight gain was related to increases in height, weight, a higher prevalence of overweight and central fat distribution. In addition, rapid weight gain was related to a higher REE in boys, but not to cardio‐metabolic risk factors.     

Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma

Introduction: There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic.

Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma. The combination of lenvatinib plus everolimus has achieved the highest rates of objective responses and the longest progression free and overall survival in cross-comparison trials. At the same time, the safety profile of this combination, including the rate of total and severe adverse events, the percentage of dose reductions required, and the rate of treatment discontinuation, was less favorable compared with available monotherapy options, suggesting that better management could help to maximize the activity of this combination while protecting patients from undue harm.

Expert opinion: Herein, we aim to postulate multidisciplinary recommendations on the advice to offer to patients and caregivers before starting treatment and how to manage the combination from the perspective of daily clinical practice.     

Structure-activity relationship studies of CNS agents. Part 29. N-Methylpiperazino-substituted derivatives of quinazoline, phthalazine and quinoline as novel α1, 5-HT1A and 5-HT2A receptor ligands

New N-methylpiperazino-substituted quinazolines 8 and 9, phthalazine 13, and quinoline 19 have been synthesized. The receptor binding profiles (α₁, 5-HT_1A, 5-HT_2A) of these compounds and their analogs (7–22) have been determined. It has been demonstrated that orientation of a local dipole moment of the heteroaromatic ring system affects both the α₁ and 5-HT_2A affinity of the investigated class of ligands. Distortion of the coplanar unfused heteroaromatic ring system results in a decreased 5-HT_2A affinity. 4-(4-Methylpiperazino)-2-(2-thienyl)quinoline 18 is the most active and selective α₁ ligand (K_i = 4.9 nM) with a much lower affinity for 5-HT_1A (K_i = 3420 nM) and 5-HT_2A (K_i = 211 nM) receptors.