Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine—I. Synthesis and purification

The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of HI across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identify of 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[¹²⁵I]stearic acid and 9- or 10-monoiodo[¹²⁵I]stearyl carnitine were synthesized via the isotopic exchange of ¹²⁵I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine.     

测定血液病患者血浆Venetoclax浓度的HPLC-MS/MS方法

目的建立测定血液病患者血浆Venetoclax浓度的HPLC-MS/MS法。方法患者血浆经甲醇(含内标Venetoclax-d8)沉淀蛋白处理。色谱柱为Ultimate@XB-C18(4.6×50 mm,5μm),柱温60℃。流动相为含0.1%甲酸和2 mmol·L^-1乙酸铵的水溶液和含0.1%甲酸的甲醇溶液,流速0.7 m L·min^-1,梯度洗脱。Venetoclax与Venetoclax-d8质谱检测方式均为电喷雾正离子模式,多反应监测(MRM),同时监测Venetoclax m/z 868.5~321.7(定量离子),Venetoclax m/z 868.5~177.6(定性离子)及Venetoclax-d8m/z 876.6~329.4(定量离子)。以Venetoclax和Venetoclax-d8峰面积比为定量依据,计算血浆Venetoclax浓度。并对该方法进行性能评价。结果Venetoclax在10~2 000 ng·mL^-1范围内线性良好,三批回归方程进行线性拟合后的标准曲线方程为Y=0.001 87 X+0.003 15,r=0.996 7;携带污染、重复性、实验室内精密度、回收率、基质效应和稳定性均符合性能验证要求。结论所建立的HPLC-MS/MS方法可准确、灵敏、快速地检测血液病患者血浆Venetoclax浓度,可应用于Venetoclax治疗药物监测及其体内药动学分析。     

Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies

At present, the only curative therapy for patients with T-cell malignancies is allogeneic stem cell transplant, which has associated risks and toxicities. Novel agents have been tried in relapsed T-cell acute lymphoblastic leukemia (T-ALL), but only one, with 20%–30% complete remission rates, has been approved by the US Food and Drug Administration. T-ALL is a heterogeneous disease, but it has universal overexpression of CD7 as well as several other T-cell markers, such as CD2 and CD5. T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown great potential for inducing both remissions and even long-term relapse-free survival in patients with B-cell leukemia and lymphoma. UCART7 for CD7⁺ T-cell malignancies is in development for treatment of relapsed T-ALL in children and adults. It may also have potential in other CD7⁺ hematologic malignancies that lack both effective therapies and targeted therapies. The challenges encountered and progress made in developing a novel fratricide-resistant “off-the-shelf” CAR-T (or UCART7) that targets CD7⁺ T-cell malignancies are discussed here.     

冠心病患者下肢动脉硬化的超声检测价值

目的:应用超声方法对已确诊的冠心病患者下肢动脉硬化情况进行检测分析,探讨研究冠心病与下肢动脉硬化之间的关系。方法:采用超声诊断仪对临床已确诊的冠心病患者101例(观察组)和非冠心病患者87例(对照组)进行检测,观察其下肢动脉粥样硬化程度,并进行比较研究。结果:观察组与对照组相比,观察组的下肢动脉血管内径显著小于对照组(P<0.05),观察组的下肢粥样斑块发生率显著高于对照组(P<0.05),观察组动脉中膜厚度显著高于对照组(P<0.05)。采用任意节段下肢动脉出现粥样硬化斑块来预测冠心病,敏感性为78.21%,特异性为81.61%,阳性检测率为83.15%,阴性预测率为76.34%。结论:下肢动脉粥样硬化与冠心病之间有着较密切的联系,下肢血管动脉硬化对冠心病的发生有一定的预测价值,尤其适于无症状人群的筛查,可为冠心病的预防、诊断、治疗提供重要信息。     

疼痛神经修复学细胞移植干预策略治疗慢性疼痛8例

目的：探讨静脉细胞移植治疗慢性疼痛的安全性和有效性,提出疼痛神经修复学干预新策略。方法：2010年3~8月,采用一次静脉输注（1.1~1.5）×107个脐带间充质基质细胞治疗8例慢性疼痛患者,使用疼痛评估采用数字评分法评定疗效。结果：7例患者在治疗后1~3 d内疼痛大部缓解或完全消失,1例30 d后明显缓解。随访时间1~6个月,无任何不良事件发生。术前疼痛平均分为（7.3±1.0）分,随访平均分为（1.1±0.2）分（P〈0.001）。结论：疼痛神经修复学细胞移植干预策略治疗慢性疼痛简便、安全,能迅速缓解严重的顽固性疼痛,是疼痛治疗的最新研究方向,前景广阔。     

针刺丰隆、曲池及三阴交对高脂血症小鼠血脂的影响

目的观察针刺丰隆、曲池及三阴交对高脂血症小鼠血脂的影响。方法将120只雄性小鼠随机分为正常组40只、模型组40只、针刺组20只及药物组20只。正常组予普通平价饲料喂养,其余3组采用高脂饮食诱导法制备高脂血症小鼠模型,连续10 d。造模成功后,针刺组予针刺双侧丰隆、曲池及三阴交,并接通韩氏电针仪,同时予2 mL/（g.d）蒸馏水灌胃;药物组将辛伐他丁胶囊6.6 mg/（g.d）予蒸馏水2mL稀释灌胃;正常组及模型组予等容积蒸馏水灌胃,连续10 d。分别于造模后第15 d取正常组、模型组小鼠各20只及治疗后取各组剩余小鼠,检测血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）含量。结果造模后第15 d模型组TC、TG和LDL-C含量均高于正常组（P〈0.05）,HDL-C含量低于正常组（P〈0.01）,提示高脂血症小鼠模型造模成功。治疗后模型组TC、TG、LDL-C含量均高于正常组（P〈0.01）,HDL-C含量低于正常组（P〈0.01）。针刺组、药物组TC、TG及LDL-C含量均低于模型组,HDL-C含量高于模型组（P〈0.05或P〈0.01）。针刺组TC、LDL-C含量均低于药物组（P〈0.05,P〈0.01）。结论针刺丰隆、三阴交、曲池穴可降低高脂血症模型小鼠血清中的TC、TG、LDL-C,升高HDL-C,具有良好的调节脂质代谢作用。     

用高效液相法测定肾特康胶囊中盐酸小檗碱的含量

目的:研究肾特康胶囊所含盐酸小檗碱的HPLC测定方法。方法:采用ThermoHypersilC18色谱柱(4.6mm×25mm,5μm);流动相:乙腈-0.33mol/L磷酸二氢钾溶液(0.5%三乙胺,磷酸调pH值至3.0)30:70;检测波长:265nm;流速:1.0mL/min。结果:盐酸小檗碱在0.2336~1.752μg范围呈良好的线性关系,r=0.9997(n=6),平均回收率98.67%,RSD=3.1%(n=5)。结论:该方法简便、准确、重现性好,可用于肾特康胶囊中盐酸小檗碱含量测定。     

针刺对高脂血症小鼠抗氧化能力及血管内皮保护功能的影响

目的:观察针刺对高脂血症小鼠的作用及作用机制.方法:将昆明雄性清洁级小鼠120只,随机分为正常组(40只)、模型组(40只)、针刺组(20只)和药物组(20R).后3组采用高脂饮食饲料喂养制备高脂血症小鼠模型.造模成功后,针刺组针刺双侧"丰隆""曲池""三阴交"穴后接通韩氏电针仪干预10 min,每日1次,连续干预10...     

益气活血散结法治疗子宫内膜异位症180例

目的:观察中药益气活血散结法治疗子宫内膜异位症的临床疗效。方法:180例子宫内膜异位症患者使用中药益气活血散结法(水煎内服及灌肠)加针灸治疗,共3个疗程(9个月)。服药前、服药1个疗程、服药2个疗程及服药3个疗程后,对疗效、痛经及非经期盆腔痛、子宫体积及卵巢内摸样囊肿进行观察研究。结果:治疗3个月后180例患者中,痊愈35例,占19.44%;显效63例,占35%;有效26例,占14.44%;无效56例,占31.11%,总有效率为68.89%。治疗6个月,痊愈46例,占25.56%;显效78例,占43.33%;有效26例,占14.44%;无效30例,占16.67%,总有效率为83.33%。治疗9个月,痊愈90例,占50.00%;显效55例,占30.56%;有效25例,占13.89%;无效10例,占5.56%,总有效率为94.44%。治疗3个月与治疗9个月的总显效率的差异有显著性差异,P≤0.05。结论:临床观察发现中药益气活血散结法治疗子宫内膜异位症能显著改善患者的临床症状,缓解疼痛,并使一部分不孕患者受孕,为保守治疗子宫内膜异位症的患者提供了良好、确切、可靠的治疗方法。     

Protein blend ingestion before allogeneic stem cell transplantation improves protein-energy malnutrition in patients with leukemia

Severe protein-energy malnutrition (PEM) and skeletal muscle wasting are commonly observed in patients with acute leukemia. Recently, the ingestion of a soy-whey protein blend has been shown to promote muscle protein synthesis (MPS). Thus, we tested the hypothesis that the ingestion of a soy-whey blended protein (BP) may improve the PEM status and muscle mass in acute leukemia patients. In total, 24 patients from the same treatment group were randomly assigned to the natural diet plus soy-whey blended protein (BP) group and the natural diet only (ND) group. Our data showed that protein and energy intake decreased significantly (P < .05) after transplantation in both groups. In the absence of the BP intervention, dramatic decreases in muscle-related indicators (i.e., anthropometric variables, muscle strength and serum protein) were observed in the majority (>50%) of the patients. However, 66% of the patients who ingested the BP before transplantation showed obvious increases in arm muscle area. The gripping power value (△_post-pre or △_{post-baseline}) was significantly higher in the BP group than in the ND group (P < .05). The ingestion of the BP also increased the levels of serum albumin, globulin and serum total protein to different extents. Notably, the average time to stem cell engraftment was significantly shorter for patients in the BP group (12.2 ± 2.0 days) than for patients in the ND group (15.1 ± 2.9 days). Collectively, our data supported that soy-whey protein can improve PEM status and muscle mass in leukemia patients.