Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

肛肠疾病手术前后肛管直肠压力测定的应用

目的:探讨肛肠疾病手术前后肛管直肠压力测定的应用。方法:将2018年5月-2019年5月在上海市松江区方塔中医医院及上海中医药大学附属曙光医院肛肠科行手术治疗的826例肛肠疾病患者作为研究对象,其中,选择性痔上黏膜吻合术246例、单纯外剥内扎术115例、外剥内扎结合内痔套扎术(Automatic Ligation of Hemorrhoids,RPH)153例、低位肛瘘切除术177例、高位肛瘘切开挂线术135例,分别于术前及术后1个月测定肛管直肠压力。结果:选择性痔上黏膜吻合术后直肠静息压、肛管静息压明显低于术前,肛管舒张压高于术前(P<0.05),但肛管最大收缩压与术前相比无明显差异(P>0.05);单纯外剥内扎术术后直肠静息压、肛管静息压明显低于术前,肛管舒张压、肛管最大收缩压明显高于术前(P<0.05);外剥内扎结合内痔套扎术术后直肠静息压、肛管静息压明显低于术前,肛管舒张压、肛管最大收缩压明显高于术前(P<0.05);低位肛瘘切除术术后直肠静息压、肛管静息压、肛管舒张压均高于术前(P<0.05),而肛管最大收缩压与术前相比无明显差异(P>0.05);高位肛瘘切开挂线术术后直肠静息压高于术前,肛管静息压、肛管舒张压低于术前(P<0.05),而与肛管最大收缩压术前相比无明显差异(P>0.05)。结论:肛肠疾病手术前后肛管直肠压力测定的应用效果显著,能准确判断手术效果及患者恢复情况,为医师的进一步诊治奠定了良好基础。     

敷料更换的不同次数对穿刺引流术后穿刺口感染的影响

目的 研究敷料更换的不同次数对穿刺引流术后穿刺口感染的影响.方法 随机将该院2013年6月—2014年7月收治的100位进行穿刺引流术的患者分为两组,50例为A组,50例为B组. 为A组患者1周更换1次敷料,B组患者1周更换2次敷料. 对两组患者穿刺口感染的情况进行分析比较. 结果 A组患者穿刺口感染的几率显著低于B组(P<0.05),A组患者的病原菌定植率显著低于B组(P<0.05),两组患者导管相关性血流感染率差异无统计学意义(P>0.05). 结论 穿刺引流术后的患者1周更换1次敷料比较合理,既能降低患者术后穿刺口感染的几率,又能降低医护人员的工作量,但要注意在敷料发生松动或者潮湿时也要及时进行更换.     

Classification and cyclic fatigue evaluation of new kinematics for endodontic instruments

This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova , P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics.     

Vacuum myofascial therapy device for non-specific neck pain. A single blind randomized clinical trial

ObjectivesThis study aimed to investigate the efficacy of a vacuum myofascial therapy device (VT) for improving pressure pain thresholds (PPTs), range of motion (ROM), neck pain-related disability, pain, and quality of life in patients with non-specific neck pain.MethodsA randomized controlled trial in which thirty-eight participants with non-specific neck pain (NP) were randomly assigned to either an experimental (VT) or a comparison physical therapy program (PTP) group. The VT group (n = 19) received five sessions of treatment with a vacuum myofascial therapy device while the PTP group (n = 19) received five sessions of massage, ultrasound therapy (US), and transcutaneous electric nerve stimulation (TENS) over two weeks. The outcome measures were the numerical pain rating scale (NPRS), range of motion, quality of life (SF-12), neck disability Index (NDI), and PPTs at the end of treatment and at one-month follow-up.ResultsAlthough both groups experienced improvements in pain, neck disability, range of motion, and pressure pain, these only were statistically significant in the VT group. At one-month follow-up, the VT group still showed improvements in pain, neck disability, and range of motion.DiscussionVacuum myofascial therapy applied with a device offers similar results to other vacuum-based techniques such as cupping therapy. Moreover, in this device the parameters are digitally controlled, which allows for the precise reproduction of treatment.     

透析液钙离子浓度对肾功能衰竭血液透析患者血清钙离子水平及血压的影响

目的 观察不同钙离子浓度的透析液对血液透析患者透析后血清钙离子水平及血压变化的影响，为肾功能衰竭血液透析患者的高钙血症及高血压的防治提供依据。方法 选择不同钙离子浓度的透析液，将维持性血液透析患者分为高钙组（1．75mmol／L）和低钙组（1．25mmol／L），比较患者每次透析前后脉搏、血压，同时抽查患者透析前后血钙及血肌酐浓度的变化。结果透析后两组患者血肌酐浓度均显著下降，透析前后差异均具有统计学意义（P〈0．01）；高钙组患者透析后血钙较透析前升高，差异具有统计学意义（P〈0．01），而低钙组患者血钙比透析前略降低，差异无统计学意义（P〉0．05）。高钙组患者透析后较透析前收缩压、舒张压及平均动脉压都升高，差异均具有统计学意义（P〈0．05），而低钙组患者透析后较透析前收缩压、舒张压及平均动脉压都降低，差异均具有统计学意义（P〈0．05）。透析后两组血钙比较差异具有统计学意义（P〈0．01）；透析后低钙组较高钙组患者的收缩压、舒张压及平均动脉压都降低，三者差异均具有统计学意义（P〈0．01）。结论透析液钙离子浓度与血液透析患者血清钙离子水平及血压呈正相关，低钙透析液透析有助于维持性血液透析患者高血压的控制。     

Perception and use of the results of patient satisfaction surveys by care providers in a French teaching hospital.

OBJECTIVE: . The aim of this study was to assess clinical staff's opinions on the results of in-patient satisfaction surveys and their use within the quality improvement process. SETTING: The institution is a 2200-bed teaching hospital of tertiary health care employing 8000 professionals. Patient satisfaction surveys are carried out each year using a validated questionnaire mailed to a random sample of patients. The specific results of each department are sent to the medical and paramedical managers. METHODS: We conducted a questionnaire survey on 500 care providers randomly selected in every medical and surgical department. RESULTS: A total of 261 questionnaires were returned and analysed. Overall, 94% of responders had a favourable opinion of the patient satisfaction surveys. They considered that the patient was able to judge hospital service quality, especially in its relational, organizational, and environmental dimensions. The specific results for the department were less well known than the overall hospital results (60 versus 76%). These results were formally discussed in the department according to 40% of responders; 40% declared that these data resulted in improvement actions and considered that they led to modifications in their behaviour with patients. CONCLUSIONS: Despite a declared interest in satisfaction surveys, the results remain underused by hospital staff and insufficiently discussed within teams.     

Wound conditioning by vacuum assisted closure (V.A.C.) in postoperative infections after dorsal spine surgery

The use of vacuum assisted closure (V.A.C.) therapy in postoperative infections after dorsal spinal surgery was studied retrospectively. Successful treatment was defined as a stable healed wound that showed no signs of acute or chronic infection. The treatment of the infected back wounds consisted of repeated debridement, irrigation and open wound treatment with temporary closure by V.A.C. The instrumentation was exchanged or removed if necessary. Fifteen patients with deep subfascial infections after posterior spinal surgery were treated. The implants were exchanged in seven cases, removed completely in five cases and left without changing in one case. In two cases spinal surgery consisted of laminectomy without instrumentation. In two cases only the wound defects were closed by muscle flap, the remaining ones were closed by delayed suturing. Antibiotic treatment was necessary in all cases. Follow up was possible in 14 patients. One patient showed a new infection after treatment. The study illustrates the usefulness of V.A.C. therapy as a new alternative management for wound conditioning of complex back wounds after deep subfascial infection.     

有关医院空调水系统若干问题的探讨

主要阐述空调水系统利用平衡阀调节系统阻力,保持系统水力稳定;利用软启动器实施水泵的平滑软启动;压差旁通阀的作用及选型安装;系统管道热膨胀等问题。     

慢性肺心病哮喘持续状态218例临床分析

目的探索治疗慢性肺心病哮喘持续状态的方法。方法回顾性分析1983年10月～2005年3月收治的218例慢性肺心病哮喘持续状态患者的临床资料。结果哮喘持续状态在48h以内被控制的62例（28．4％）；在72h以内控制的56例（25．7％）；在120h以内控制的25例（11．5％）；在168h以内控制的34例（15．6％）；痊愈出院177例（81．2％）；死亡41例（18．8％）。结论（1）治疗慢性肺心病哮喘持续状态．根据患者的病理变化．综合治疗．效果显著。（2）在治疗过程中．要恰当选择抗生素和平喘药；对那些血液黏滞度增高的患者．要加用血液稀释疗法。（3）测定血液黏滞度和氧饱和度．可以指导治疗、估计预后．应当列为常规检查。