Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

HBV感染免疫耐受期孕妇分娩前后 临床指标及细胞因子水平变化特征

[摘要]　目的　分析HBV感染免疫耐受期孕妇分娩前后临床指标及细胞因子水平的变化规律，比较分娩后不同ALT水平组孕妇血清细胞因子水平差异。方法　选择2015年1月—2017年12月就诊于首都医科大学附属北京佑安医院的HBV感染免疫耐受期孕妇52例，妊娠28周给予替比夫定（telbivudine, LdT）抗病毒干预，分别于LdT干预前（基线）、分娩前（2周）及分娩后（6周）进行生化、血清学及病毒学检测，同步留取相应时间点外周血标本进行细胞因子检测，并分析分娩前后临床指标及细胞因子水平的变化特征。结果　52例患者分娩后6周ALT水平均值明显高于LdT干预前和分娩前，其中ALT≥2倍正常值上限（upper limit of normal, ULN）者达28.8%（15/52例）；与LdT干预前相比，分娩前HBV DNA水平显著下降，平均降幅达（3.68±0.79） lg IU/ml；HBsAg和HBeAg水平在分娩前后无明显变化。与分娩后ALT＜2倍ULN组相比，ALT≥2倍ULN组的IFN-γ水平在LdT干预前呈低水平表达，分娩后呈高水平表达，差异均有统计学意义（Z=2.284，P=0.022；Z=2.223，P=0.026）；2组间IL-2、IL-4、IL-6、IL-10、TNF-α在LdT干预前、分娩前及分娩后均无明显差异。结论　HBV感染免疫耐受期孕妇分娩后部分患者ALT明显升高，结合分娩前后细胞因子的动态变化，提示分娩后可能出现免疫功能增强并打破机体对HBV的免疫耐受，这或许有利于分娩后的抗病毒治疗，但仍须要进一步深入的研究。     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

乳果糖口服溶液联合谷氨酸钾注射液治疗肝性脑病的疗效观察

目的探讨乳果糖口服溶液联合谷氨酸钾注射液治疗肝性脑病的临床疗效。方法选取2014年4月—2017年4月在天门市第一人民医院治疗的肝性脑病患者114例为研究对象,将所有患者随机分为对照组和治疗组,每组各57例。对照组静脉滴注谷氨酸钾注射液,60 mL加入到生理盐水500 mL中,1次/d。治疗组在对照组的基础上口服乳果糖口服溶液,30 mL/次,3次/d。两组患者均连续治疗7 d。观察两组的临床疗效,比较两组的生化学指标和Child-Pugh评分。结果治疗后,对照组和治疗组的总有效率分别为75.44%、92.98%,两组比较差异具有统计学意义(P0.05)。治疗后,两组血氨、总胆红素(TBil)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转氨酶(AST)水平均显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些生化学指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组Child-Pugh评分均显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组Child-Pugh评分明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论乳果糖口服溶液联合谷氨酸钾注射液治疗肝性脑病具有较好的临床疗效,能改善精神状况,降低血氨水平,改善肝脏功能,安全性较好,具有一定的临床推广应用价值。     

Transaminases in the acquired pellicle

Objective

Transaminases (AST, aspartate amino transferase; ALT, alanine amino transferase) are relevant enzymes in physiology and pathology of the human organism. The aim of the present in situ study was to demonstrate the presence of these enzymes in the enamel pellicle.

Methods

Bovine enamel slabs were fixed on buccal sites of individual upper jaw splints and worn for 3, 30 and 120 min by 5 subjects to allow pellicle formation. The in situ pellicles were tested for AST and ALT. Enzyme activities were measured photometrically via determination of the products pyruvate and oxalacetate using lactate-dehydrogenase and malate-dehydrogenase, respectively.

Results

Enzymatic AST- as well as ALT-activities are present in the acquired pellicle within 3 min. The enzyme activities exposed at the pellicles’ surfaces increased slightly with the pellicle formation time (ANOVA, AST: n.s., ALT: p = 0.021). However, the two enzymes show considerable intraindividual and interindividual variability. The mean AST-activity of the pellicle amounted to 1.07 ± 0.81 mU/cm² (ALT 1.18 ± 0.52 mU/cm²). The ALT-activity of the centrifuged saliva was 26.62 ± 11.09 mU/ml (AST 35.98 ± 29.35 mU/ml).

Conclusions

AST as well as ALT are present in the in situ pellicle layer and may contribute to the intrinsic maturation of pellicle proteins.