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。     

乙型肝炎病毒对不同ALT状态下慢性乙型肝炎患者T淋巴细胞及其亚群的影响

目的：探讨乙型肝炎病毒（HBV）在不同丙氨酸氨基转移酶（ALT）状态下对T淋巴细胞及其亚群的影响,阐明以ALT分组抗病毒治疗乙型肝炎（乙肝）的免疫学机制。方法：选取慢性乙肝患者363例作为研究对象,根据ALT异常情况分为ALT正常组（131例）、ALT大于等于正常上限且小于2倍增高组（110例）和ALT大于等于正常上限2倍增高组（122例）。对ALT大于等于正常上限2倍增高组患者给予恩替卡韦治疗,随访24周。采用化学发光免疫分析仪检测乙肝抗原抗体指标,采用全自动生化分析仪检测肝功能指标,采用全自动荧光定量PCR分析仪检测被测者的病毒载量,采用流式细胞仪检测T淋巴细胞分类,酶联免疫吸附实验（ELISA）法检测患者血清中白细胞介素12（IL-2）、干扰素γ（IFN-γ）、白细胞介素4（IL-4）和白细胞介素10（IL-10）水平,检测不同组别中不同载量HBV对机体免疫学指标的影响及抗病毒治疗前后患者病毒学及免疫学指标的变化。结果：在ALT正常组中,不同载量HBV患者T淋巴细胞总数、Th/i淋巴细胞数、Ts/c淋巴细胞数及血清中IL-2、IFN-γ、IL-4和IL-10水平比较差异无统计学意义（P>0.05）;在ALT大于等于正常上限2倍增高组,随着病毒载量的增加,患者T淋巴细胞总数和Th/i淋巴细胞数明显下降（P<0.05）,Ts/c淋巴细胞数明显升高（P<0.05）,反映Th1细胞的细胞因子IL-2和IFN-γ水平明显升高（P<0.05）,反映Th2细胞的细胞因子IL-4和IL-10水平明显下降（P<0.05）。与治疗前比较,恩替卡韦治疗24周后,患者HBVDNA明显下降（P<0.05）,T淋巴细胞总数和Th/i淋巴细胞数明显升高（P<0.05）,Ts/c淋巴细胞数明显下降（P<0.05）,血清中IL-2和IFN-γ水平明显下降（P<0.05）,IL-4和IL-10水平明显升高（P<0.05）。结论：HBV在不同ALT状态下对机体免疫功能有不同的影响,对于ALT大于等于正常上限2倍增高的乙肝患者进行抗病毒治疗可明显改变机体的免疫状态。     

ALT小于2倍正常上限的HBeAg阴性慢性HBV感染者肝脏病理改变及相关因素分析

目的探讨ALT小于2倍正常值上限(upper limits of normal,ULN)的HBeAg阴性慢性HBV感染者中与肝脏病理学改变相关的临床指标。方法将60例ALT2×ULN的HBeAg阴性慢性HBV感染者按照不同肝脏炎症程度及纤维化程度分组,对比各组患者性别比例、年龄、血清ALT、HBV DNA定量、脾脏厚度、门静脉内径、肝脏瞬时弹性探测仪(FibroScan)测定肝硬度值(liver stiffness measurement,LSM)的变化情况。结果 60例患者肝脏炎症改变在G1~G3级,纤维化程度在S0~S2期,其中≥G2、达S2者分别为49例(81.7%)、19例(31.7%)。60例患者中,随着肝脏炎症及纤维化程度的加重,男性患者比例、年龄、脾脏厚度、门静脉内径、LSM值均明显增加,差异均有统计学意义(P均0.05);血清ALT水平、HBV DNA定量随肝脏炎症程度的加重亦明显增加,差异均有统计学意义(P均0.05),但以上两指标随肝脏纤维化程度的加重无明显变化。结论对于ALT2×ULN的HBeAg阴性慢性HBV感染者,仍然有相当部分患者的肝脏病变在G2或/和S2以上,对于这部分人群,尤其是男性患者,密切随访年龄、血清ALT、HBV DNA、脾脏厚度、门静脉内径、LSM值的变化对于协助了解肝脏病理变化有一定的提示作用。     

Effects of sodium-glucose co-transporter-2 inhibitors on serum alanine aminotransferase levels in people with type 2 diabetes: A multi-institutional cohort study

Clinical trials have indicated that sodium-glucose co-transporter-2 (SGLT2) inhibitors have a favourable effect on serum alanine aminotransferase (ALT) levels in people with type 2 diabetes (T2D), but supporting evidence from real-world studies is lacking. We identified patients with T2D who initiated SGLT2 inhibitors during the period 2016 to 2017 from Chang Gung Research Database, which covers 1.3 million individuals from seven hospitals (6% of the Taiwan population). We classified patients by baseline ALT level and evaluated changes in ALT values from baseline to 1 year after initiation of SGLT2 inhibitors. We identified 11 690 new users of SGLT2 inhibitors with a mean (SD) age of 59.3 (11.8) years. The mean (SD) glycated haemoglobin and ALT levels were 8.9 (1.7)% and 34.7 (28.9) U/L at baseline, respectively. The mean change in ALT levels was −5.0 U/L (95% confidence interval [CI] –6.4, −3.5) 1 year after initiation of SGLT2 inhibitors. In patients with ALT levels ≤1× the upper limit of normal (ULN), the change in ALT levels was 1.6 U/L (95% CI –0.1, 3.4), while in those with ALT levels >1× ULN, the change in ALT levels was −26.5 U/L (95% CI –28.6, −24.3). The higher the baseline ALT level, the greater the decline after SGLT2 inhibitor treatment. Our findings suggest the initiation of SGLT2 inhibitors for T2D management could improve serum ALT levels in clinical practice, particularly in patients with especially high ALT levels.