A retrospective analysis of 140 patients with giant cell tumor in the extremity: A multicenter study based on four hospitals in South China

Background: Update reports are rarely available regarding the bone giant cell tumors (GCTs) in the extremity in Chinese people. The aim of this study was to review the epidemiological characteristics of bone GCT in the extremity based on the clinical data from four hospitals in South China. Methods: We searched medical electronic records from January 2001 to December 2011 in four hospitals in South China to identify patients with definite diagnosis of extremity GCT. Epidemiological data including gender, tumor site, age at the time of first diagnosis, local recurrence and pulmonary metastasis were collected and analyzed statistically. Differences between-genders were particularly analyzed regarding first diagnosis age, tumor site, local recurrence and pulmonary metastasis. T-test and Chi-square test were used for continuous and dichotomous variables, respectively. Results: A total of 140 GCT patients (87 males and 53 females) were identified. The gender ratio was 1.64 for a male predominance. GCTs were mostly located around the knee (67 cases). 92 patients were in their 20s to 40s upon first diagnosis. The average age at the time of first diagnosis for all was 30.49 years, 30.76 years for males and 30.06 years for females (P = 0.757). GCT recurred locally in 50 patients (26 males and 24 females) with no gender difference (P = 0.065). The average interval from first surgery to local recurrence was 21.42 months. Pulmonary metastasis was found in 11 patients (8 males and 3 females) also with no gender difference (P = 0.667). The average interval from first diagnosis to metastasis was 36.45 months. Conclusions: Extremity GCT may have a male predominance in Chinese population and mostly occur at 20–40 years of age and around the knee. Follow-ups for GCT patients should be carried on for at least 3 years after primary surgery according to the average intervals for possible local recurrence and pulmonary metastasis.     

从国家自然科学基金项目资助看植物科学态势

通过对2010-2015年度国家自然科学基金委员会生命科学部植物学学科资助的各类项目进行统计分析,总结了植物学学科资助的整体概况,详细分析了各类科学基金项目的资助特点、在不同分支学科和领域中的分布以及获资助排名前列的依托单位,并展望了我国未来植物学学科的发展趋势。     

Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study

ObjectivesThe primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy.MethodsA prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated.ResultsEighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.ConclusionSpent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients.     

CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1

Cytochrome P450 epoyxgenase 2J2 and epoxyeicosatrienoic acids (EETs) are known to protect against cardiac hypertrophy and heart failure, which involve the activation of 5′‐AMP‐activated protein kinase (AMPK) and Akt. Although the functional roles of AMPK and Akt are well established, the significance of cross talk between them in the development of cardiac hypertrophy and antihypertrophy of CYP2J2 and EETs remains unclear. We investigated whether CYP2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1. Moreover, we tested whether EETs enhanced cross talk between AMPKα2 and phosphorylated Akt1 (p‐Akt1), and stimulated nuclear translocation of p‐Akt1, to exert their antihypertrophic effects. AMPKα2^?/? mice that overexpressed CYP2J2 in heart were treated with Ang II for 2 weeks. Interestingly, overexpression of CYP2J2 suppressed cardiac hypertrophy and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild‐type mice but not AMPKα2^?/? mice. The CYP2J2 metabolites, 11,12‐EET, activated AMPKα2 to induce nuclear translocation of p‐Akt1 selectively, which increased the production of ANP and therefore inhibited the development of cardiac hypertrophy. Furthermore, by co‐immunoprecipitation analysis, we found that AMPKα2β2γ1 and p‐Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain. This interaction was enhanced by 11,12‐EET. Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hypertrophy and suggest that overexpression of CYP2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure.     

Resolution of Rac‐Bambuterol via Diastereoisomeric Salt Formation with o‐Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles

In this study an enantioseparation method for rac‐bambuterol (5‐(2‐(tert‐butylamino)‐1‐hydroxyethyl)‐1,3‐phenylene bis(dimethylcarbamate)) via diastereoisomeric salt formation with o‐chloromandelic acid was developed. The enantiomeric excess (ee) values and chemical purities of the desired products were confirmed by high‐performance liquid chromatography (HPLC) using chiral stationary phase and reverse‐phase HPLC analyses, respectively. The ee values and the chemical purities both exceeded 99%. Animal experiments showed that (R)‐bambuterol was a potent inhibitor for histamine‐induced asthma reactions. (S)‐bambuterol was ineffective in relaxing the airways. Both enantiomers increased heart rates in beagles. Therefore, replacing rac‐bambuterol with (R)‐bambuterol could be beneficial for asthma patients. Chirality 28:306–312, 2016. © 2016 Wiley Periodicals, Inc.