Different metabolic profiles of K1 serotype and non-serotype K1 and K2 Klebsiella pneumoniae isolates in oral infection mice model

K1 or K2 serotype Klebsiella pneumoniae isolate caused clinical pyogenic liver abscess (KLA) infection is prevalent in many areas. It has been identified that K1 or K2 serotype K. pneumoniae isolates caused KLA infection in mice by oral inoculation. In our study, K1 serotype K. pneumoniae isolate Kp1002 with hypermucoviscosity (HV)-positive phenotype caused KLA infection in C57BL/6 mice by oral inoculation. Simultaneously, non-serotype K1 and K2 isolate Kp1014 with HV-negative phenotype failed to cause KLA infection in the same manner. It seems that gastrointestinal tract translocation is the pathway by which K1 or K2 serotype K. pneumoniae caused KLA infection. Liquid chromatography-tandem mass spectrometry was used to further analyze metabolic profile changes in mice with KLA infection. Data showed that after Kp1002 or Kp1014 oral inoculation, serum Phosphatidylcholine (PC) and Lysophosphatidylcholine (LPC) levels significantly changed in mice. Some PC and LPC molecules showed changes both in the Kp1002 KLA group and the Kp1014 no-KLA group compared with the control group. The level of 18:1/18:2-PC significantly changed in the Kp1002 KLA group compared with the control group, but showed no change between the Kp1014 no-KLA group and the control group. The level of 18:1/18:2-PC might have been particularly affected by KLA infection caused by K1 serotype K. pneumoniae Kp1002. It may be a potential biomarker for KLA infection.     

血脂康对不稳定型心绞痛伴肝酶升高患者的疗效与安全性

目的探讨血脂康对不稳定型心绞痛伴肝酶升高患者的疗效与安全性。方法纳入96例服用阿托伐他汀后引起肝酶升高3倍以上的不稳定型心绞痛患者。随机均分为3组,每组32例患者,A组停阿托伐他汀;B组阿托伐他汀减半;C组更换为血脂康。总疗程为4周,治疗前后测定总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三脂(TG)、高敏C反应蛋白(hs-CRP)、丙氨酸转氨酶(ALT)。随访主要不良心血管事件(MACEs),包括心源性死亡、致死性心肌梗死(MI)、非致死性MI、猝死发生情况。结果与治疗前比较,治疗4周后三组患者ALT水平均显著下降,治疗前后比较有统计学差异(P0.05),A、C组患者ALT水平下降较B组患者更显著,与B组患者比较有统计学差异(P0.05),A、C组之间ALT水平比较,无统计学差异(P0.05)。B、C组患者治疗4周后TC、LDL-C、TG、hs-CRP水平均下降,治疗前后比较有统计学差异(P0.05);C组患者HDL-C水平较治疗前升高(P0.05),治疗前后比较有统计学差异(P0.05);A组患者TC、LDL-C、TG、hs-CRP水平下降不明显,治疗前后比较无统计学差异(P0.05)。与A组患者治疗后比较,C组患者TG、hs-CRP水平明显下降,差异有统计学意义(P0.05)。A组、B组、C组MACEs事件发生率分别为12.5%、9.4%、3.1%,组间比较差异有统计学意义(P0.05)。结论他汀引起肝酶显著升高的不稳定型心绞痛患者,换用血脂康安全有效。本研究入选患者病例数较少,有待更多的试验证实。     

Recent progress in allosteric modulators for GluN2A subunit and development of GluN2A‐selective nuclear imaging probes

N‐methyl‐D‐aspartate (NMDA) receptors play key roles in physiology by regulating the synaptic plasticity and the cellular mechanism involved in learning and memory. The GluN2A subunit is the most abundant expression of NMDA receptors in mature brain, and its dysfunction has been implicated in various neurological disorders. However, the function of GluN2A subunit in physiological and pathological conditions is not yet completely unveil due to the lack of subunit‐selective ligands, including specific positron emission tomography (PET)/single photon emission computed tomography (SPECT) imaging probes. In this review, recent progresses in understanding its pathophysiological role, the structure‐activity relationship, and the postulated mechanisms of novel GluN2A ligands as well as status of molecular imaging probes for PET are summarized.