Kallistatin Ameliorates Influenza Virus Pathogenesis by Inhibition of Kallikrein-Related Peptidase 1-Mediated Cleavage of Viral Hemagglutinin

Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses.     

血浆替代血清行常规生化检测缩短正流转时间的可行性探讨

目的探讨肝素锂抗凝血浆替代血清进行常规生化检测缩短正流转时间(TAT)的可行性。方法应用日立H7600-20全自动生化分析仪对抽取的110例患者肝素锂抗凝血浆和血清中的35项生化检测结果进行比对分析。结果在肝素锂抗凝血浆与血清的35项生化检测结果中,清蛋白(ALB)、γ-谷氨酰基转移酶(GGT)、总胆汁酸(TBA)、总胆红素(TB)、氯(Cl)、钙(Ca)、镁(Mg)、肌酐(CRE)、尿素(BUN)、尿酸(UA)、胱抑素C(CysC)、β2-微球蛋白(β2-MG)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)和高密度脂蛋白胆固醇(HDL-C)共16项指标的检测结果比较差异无统计学意义(P0.05);而钠离子(Na+)、钾离子(K+)、二氧化碳(CO2)、磷(P)、铁(Fe)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总蛋白(TP)、前清蛋白(PreA)、α-L-岩藻糖苷酶(AFU)、三酰甘油(TG)、总胆固醇(TCH)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、脂蛋白a[Lp(a)]、血糖(GLU)、直接胆红素(DB)共19项指标的检测结果比较差异有统计学意义(P0.05)。结论肝素锂抗凝血浆与血清中常规生化检测结果不完全一致,肝素锂抗凝血浆可选择性地替代血清进行部分急诊生化检测以缩短TAT。     

Serum lipid profiles: novel biomarkers predicting advanced prostate cancer in patients receiving radical prostatectomy

This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer (PCa). We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy (RP) and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score (pGS), pathological stage and lymph node involvement (LNI) in RP specimens. Preoperative prostate-specific antigen (PSA) levels, biopsy GS (bGS), and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic (ROC) curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 (95% confidence interval [CI] 1.510–27.010), 3.270 (95% CI: 1.470–7.278) for high levels of TG for pT3–4 disease, and 2.670 (95% CI: 1.134–6.287) for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.     

腹腔镜联合胆道镜经胆囊管治疗胆总管结石的疗效观察

【摘要】〓目的〓评价腹腔镜联合胆道镜经胆囊管治疗胆总管结石的疗效。方法〓回顾性分析2012年1月至2014年9月在广东医学院附属福田医院治疗的195例胆总管结石患者,按照术式分为腹腔镜联合术中胆道镜经胆囊管胆道探查取石术(LTCBDE)组(43例)、腹腔镜胆道探查“T”管引流(LCBDE)组(65例)和剖腹胆囊切除、胆总管探查取石、“T”管引流术(OCBD)组(87例)。比较三组患者手术时间、术中出血量、术后肛门排气时间、视觉模拟评分法(VAS)评分、并发症发生率,以及三组治疗前后CRP、PA、TBIL和ALT水平的变化。结果〓3组患者均成功进行手术,LTCBDE组除手术时间比OCBD组长外,术中出血量、术后VAS评分、肛门排气时间、术后住院时间和并发症明显少于LCBDE和OCBD组(P<0.001)。LTCBDE组的并发症发生率为4.7%,明显低于LCBDE组的15.4%和OCBD组的23.0%,差异有统计学意义(P<0.05)。治疗后,三组的CRP、TBIL和ALT水平比治疗前明显降低(P<0.001),而PA水平比治疗前明显升高(P<0.001)。LTCBDE组的降低和升高水平比其余两组更为明显(P<0.001)。结论〓LTCBDE具有创伤小、并发症少、费用低、术后生活质量高等优点,是一种有效、安全及经济的术式。     

吉非替尼治疗转移性乳腺癌个案报道及文献复习

【摘要】〓我国乳腺癌的发病率在女性恶性肿瘤里发病率居于第1位。分子靶向治疗药物成为近年来肿瘤治疗中的一大热点,表皮生长因子受体酪氨酸激酶抑制剂吉非替尼是EGFR敏感突变型非小细胞肺癌的标准一线治疗。近几年国外有临床研究显示吉非替尼对乳腺癌有一定治疗效果,但目前国内此类相关临床研究较少。现将我科诊治的一例吉非替尼治疗转移性乳腺癌的病例报告如下并做文献复习。     

Dual effects of atmospheric pressure plasma jet on skin wound healing of mice

Cold plasma has become an attractive tool for promoting wound healing and treating skin diseases. This article presents an atmospheric pressure plasma jet (APPJ) generated in argon gas through dielectric barrier discharge, which was applied to superficial skin wounds in BALB/c mice. The mice (n = 50) were assigned randomly into five groups (named A, B, C, D, E) with 10 animals in each group. Natural wound healing was compared with stimulated wound healing treated daily with APPJ for different time spans (10, 20, 30, 40, and 50 seconds) on 14 consecutive days. APPJ emission spectra, morphological changes in animal wounds, and tissue histological parameters were analyzed. Statistical results revealed that wound size changed over the duration of the experimental period and there was a significant interaction between experimental day and group. Differences between group C and other groups at day 7 were statistically significant (p < 0.05). All groups had nearly achieved closure of the untreated control wounds at day 14. The wounds treated with APPJ for 10, 20, 30, and 40 seconds showed significantly enhanced daily improvement compared with the control and almost complete closure at day 12, 10, 7, and 13, respectively. The optimal results of epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition in histological aspect were observed at day 7. However, the wounds treated for 50 seconds were less well healed at day 14 than those of the control. It was concluded that appropriate doses of cold plasma could inactivate bacteria around the wound, activate fibroblast proliferation in wound tissue, and eventually promote wound healing. Whereas, over doses of plasma suppressed wound healing due to causing cell death by apoptosis or necrosis. Both positive and negative effects may be related to the existence of reactive oxygen and nitrogen species (ROS and RNS) in APPJ.