高效液相色谱测定大鼠早孕组织多胺的含量

建立大鼠早孕组织中多胺含量HPLC测定的方法。方法：大鼠早孕组织中多胺用10％三氯乙酸提取，苯甲酰氯柱前衍生，反相HPLC测定。结果：多胺中腐胺、精脒和精胺能较好分离；腐胺检测限可达1nmol、精脒和精胺可达5nmol；腐胺在1～1000nmol、精脒和精胺在5～1000nmol范围内线性良好；腐胺、精脒和精胺平均生物样本回收率分别为95．8％、92．8％和81．7％，日内变异系数（CV％）分别为2．46％、1．35％和1．94％，日间变异系数分别为3．49％、1．48％和3．27％。结论：该方法简便、灵敏，完全能满足大鼠早孕组织中多胺含量测定的需要。     

Pharmacokinetics of Cefozopran by Single and Multiple Intravenous Infusions in Healthy Chinese Volunteers

Background and Objectives

Cefozopran is a parenteral cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The objective of this study was to evaluate the pharmacokinetics of cefozopran after single- and multiple-dose intravenous administration in healthy subjects, to provide clinical guidance in its application.

Methods

This was a single-center, open-label, randomized, two-phase study conducted in 12 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.5, 1.0 and 2.0 g of injected cefozopran hydrochloride in a three-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects received 2.0 g every 12 h for 4 days. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study.

Results

Twelve healthy volunteers (six males and six females) were enrolled and completed the study. Following a single 1-h intravenous infusion of 0.5, 1.0 or 2.0 g cefozopran, maximum plasma concentration (C_max) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUC_last) increased in a dose-proportional manner. The mean half-life in plasma (t_½) was in the range of 1.20–2.80 h. Cefozopran was mainly excreted in its unchanged form, with no tendency for accumulation, via the kidney, and varied from 65.99 to 73.33 %. No appreciable accumulation of either drug occurred with multiple intravenous doses of cefozopran, and pharmacokinetic parameters for cefozopran were similar on days 1 and 4. No serious adverse events were reported. Adverse events were generally mild.

Conclusion

Cefozopran was safe and well tolerated in the volunteers and displayed linear increases in the C_max and AUC_last values.     

22例Stanford B型主动脉夹层腔内隔绝术的围手术期护理

目的探讨Stanford B型主动脉夹层腔内隔绝术的围手术期护理要点。方法回顾性分析22例行胸主动脉腔内修复术的Stanford B型主动脉夹层患者的临床资料,总结护理经验。结果 22例患者手术经过顺利,术后出现1例逆行性A型夹层,15例体温过高,予对症治疗后恢复。患者均治愈出院,术后3个月随访,均未出现Ⅰ型内漏。结论术前做好心理护理,控制血压,术后继续控制血压,做好并发症护理,加强饮食及活动指导,是促进患者早期康复出院的关键。     

Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory Brainstem Implants

Background:

The auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients. The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device. This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta).

Methods:

Six adult rhesus macaque monkeys (M. mulatta) were included. Under general anesthesia, a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach. The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site. After the operation, the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy, respectively. The subjects underwent behavioral observation for 6 months, and the postoperative EABR was tested every two weeks from the 1^st month after implant surgery.

Result:

The implant surgery lasted an average of 5.2 h, and no monkey died or sacrificed. The averaged latencies of peaks I, II and IV were 1.27, 2.34 and 3.98 ms, respectively in the ABR. One-peak EABR wave was elicited in the operation, and one- or two-peak waves were elicited during the postoperative period. The EABR wave latencies appeared to be constant under different stimulus intensities; however, the amplitudes increased as the stimulus increased within a certain scope.

Conclusions:

It is feasible and safe to implant ABIs in rhesus macaque monkeys (M. mulatta) through a modified suboccipital RS approach, and EABR and CT are valid tools for animal model establishment. In addition, this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.     

Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized,placebo-controlled, 26-week trial in patients with type 2 diabetes

AimsTo assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (≥ 1500 mg/day) and pioglitazone (≥ 30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A_1c [HbA_1c] ≥ 7.5% and ≤ 11%).MethodsThis placebo-controlled, double-blind study included 313 patients, mean baseline HbA_1c = 8.7%, who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks.ResultsThe addition of sitagliptin led to significant (P < .001) mean changes from baseline relative to placebo in HbA_1c (? 0.7%), fasting plasma glucose (? 1.0 mmol/L), and 2-h post-meal glucose (? 2.2 mmol/L). In patients with baseline HbA_1c ≥ 9.0%, mean changes from baseline in HbA_1c were ? 1.6% and ? 0.8% for the sitagliptin and placebo groups, respectively (between-group difference ?0.8%; P < .001). The incidences of reported adverse events were generally similar between the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%] and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P = .786). Two patients, both in the placebo group, experienced an episode of hypoglycemia that required non-medical assistance.ConclusionsIn this 26-week study, addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated.     

A nonparametric method for value function guided subgroup identification via gradient tree boosting for censored survival data

In randomized clinical trials with survival outcome, there has been an increasing interest in subgroup identification based on baseline genomic, proteomic markers, or clinical characteristics. Some of the existing methods identify subgroups that benefit substantially from the experimental treatment by directly modeling outcomes or treatment effect. When the goal is to find an optimal treatment for a given patient rather than finding the right patient for a given treatment, methods under the individualized treatment regime framework estimate an individualized treatment rule that would lead to the best expected clinical outcome as measured by a value function. Connecting the concept of value function to subgroup identification, we propose a nonparametric method that searches for subgroup membership scores by maximizing a value function that directly reflects the subgroup-treatment interaction effect based on restricted mean survival time. A gradient tree boosting algorithm is proposed to search for the individual subgroup membership scores. We conduct simulation studies to evaluate the performance of the proposed method and an application to an AIDS clinical trial is performed for illustration.     

山东省新型冠状病毒肺炎老年病例的流行病学特征

目的初步分析山东省新型冠状病毒肺炎(COVID-19)老年病例的流行病学特征,为制定相应的疾病防控措施和对策提供理论依据。方法对2020年1月22日0:00时至2月16日24:00时山东省及省内各地市卫生健康委员会官方公示的关于新型冠状病毒(2019-nCoV)疫情信息数据库进行分析,初步探讨该病老年病例在山东省的流行病学特征。采用SPSS 20.0进行统计分析。结果纳入人群年龄(68.6±8.2)岁。截至2020年2月16日24:00时,山东省确诊老年病例95例,发病率为0.430/10万,治愈率为6.32%,病死率为2.11%。发病高峰是1月30日至2月9日。青岛病例最多(13例,13.68%),日照市病例最少(1例,1.05%),省内不同地区的老年发病率比较,差异有统计学意义(χ^2=86.370,P<0.05)。60~69岁组、70~79岁组、80~89岁组、≥90岁组COVID-19发病率分别为0.463/10万、0.386/10万、0.041/10万、0.415/10万,差异亦有统计学意义(χ^2=27.628,P<0.05)。COVID-19病例女多男少,男、女性别比为0.7∶1.0,但发病率比较差异无统计学意义(0.379/10万和0.501/10万,χ^2=0.813,P>0.05)。此外,不同合并症数目的老年COVID-19发病率亦存在显著差异(F=82.557,P<0.05)。患者聚集性发病特征明显,占比为67.37%(64/95)。平均潜伏期为6.3 d。结论山东省2019-nCoV老年人发病处于相对较低水平,2020年1月22日出现首例后,发病高峰集中在1月30日至2月9日,2月10日起发病人数逐渐减少。病例男少女多,呈现聚集性发病特点,接下来应对本地人际传播防控工作进行重点安排。     

低相对分子质量肝素对牛晶状体上皮细胞在人工晶状体表面增殖的影响

目的　体外比较研究低相对分子质量肝素 (lowmolecularweightheparin ,LMWH)和普通肝素影响牛晶状体上皮细胞 (bovinelensepithelialcell,BLEC)在聚甲基丙烯酸甲酯 (polymethylmethacrylate,PMMA)人工晶状体表面增殖的作用。方法　体外将BLEC接种到PMMA人工晶状体表面培养 ,LMWH组和肝素组培养液中分别含LMWH(1× 10 5U/L)和普通肝素 (1× 10 5U/L) ,对照组培养液中不含上述药物。 72h后用流式细胞仪对人工晶状体表面黏附的细胞进行计数分析。结果　经LMWH和普通肝素处理的PMMA人工晶状体表面BLEC形态幼稚 ,对照组BLEC呈纤维化趋势 ;细胞计数对照组为(878 2± 10 7 8)个 /ml,肝素组为 (5 4 5 5± 5 8 2 )个 /ml,LMWH组为 (40 7 8± 36 6 )个 /ml,3个组比较差异有非常显著意义 (P <0 0 0 1)。结论　LMWH可显著抑制晶状体上皮细胞在人工晶状体表面的黏附和增殖 ,有望成为更为安全、有效的防治后发性白内障的药物