柴胡解毒汤治疗尖锐湿疣的疗效观察和机制探讨

目的:观察柴胡解毒汤治疗尖锐湿疣（CA）的临床疗效和探讨其部分起效机制。方法:将2015年6月至2017年9月浙江大学医学院附属杭州市第一人民医院皮肤科门诊就诊的120例CA病例（年龄16～65岁）随机分为A组、B组和C组,每组40例。A组采用柴胡解毒汤治疗（n=40）,100 mL口服,2次/日,连续治疗30 d为1个疗程;B组采用α-2b重组人干扰素治疗（n=39,其中1位病例用药2周后因不良反应退出研究）,300万IU肌肉注射,隔天1次,注射15次为1个疗程;C组不采用任何全身系统治疗方案（n=40）。比较3组病例临床疗效,统计复发率和复发次数,以及药物不良反应情况。检测A组病例口服柴胡解毒汤治疗前后外周静脉血中T淋巴细胞亚群及NK细胞百分率,血清中细胞因子IL-2、IL-4、IL-10、IL-12、IFN-γ的蛋白表达水平。结果:除B组1位退出研究病例,随访12周复发率和复发次数,总病例中复发率为51.26%（61/119）,平均复发次数为1.6次。其中A组病例和B组病例的复发率和复发次数均低于C组病例（P<0.01）;A组病例和B组病例之间的复发率和复发次数无统计学差异（P>0.05）。与口服柴胡解毒汤治疗前相比,治疗一个月后的CA病例外周血CD4+T淋巴细胞百分率升高,CD4+/CD8+比值升高,NK细胞百分率升高（P均<0.01）;而CD3+T淋巴细胞百分率和CD8+T淋巴细胞百分率的差异均无统计学意义。与口服柴胡解毒汤治疗前相比,治疗后的CA病例外周血清IL-2、IL-12、IFN-γ增多（P<0.01）,IL-10下降（P<0.05）,而IL-4含量的差异无统计学意义（P>0.05）。结论:柴胡解毒汤治疗CA的临床疗效确切,与肌注α-2b重组人干扰素相当,其起效机制可能是通过促进CD4+T淋巴细胞数量和功能改善细胞免疫功能,并通过促进CD4+T细胞分泌的细胞因子IL-2、IFN-γ增加而实现NK细胞数量增多和功能活化。     

托珠单抗与依那西普治疗多关节炎型幼年特发性关节炎临床研究

目的:探讨托珠单抗与依那西普治疗多关节炎型幼年特发性关节炎（polyarticular juvenile idiopathic arthritis,pJIA）患儿的临床疗效,免疫调节作用及安全性差异。方法:选择2017年1月至2019年3月在浙江大学医学院附属儿童医院诊治的24例重度活动性pJIA患儿,分为托珠单抗组12例和依那西普组12例,分别记录两组患儿治疗前、治疗3个月、6个月、12个月时的临床症状、实验室指标及不良反应情况,并进行对比分析。结果:治疗3个月时,托珠单抗组和依那西普组的关节肿胀数、关节压痛或活动时疼痛数、C反应蛋白（CRP）、红细胞沉降率（ESR）及JADAS 27评分均较治疗前有明显改善（P<0.05）;且托珠单抗组的CRP、ESR、JADAS 27评分比依那西普组下降更明显（P<0.05）。治疗6个月时,托珠单抗组CD19+B、CD4+T细胞比例、IgG、IgA、IgM、C3、C4下降和CD8+T细胞比例升高,比较治疗前差异有统计学意义;依那西普组IgG和IgA较治疗前明显下降;托珠单抗组IgG、IgA、IgM、C3、C4比依那西普组下降更明显（P<0.05）。治疗12个月时,托珠单抗组和依那西普组的JADAS 27低疾病活动度率分别为36.4%和37.5%;两组的ACR Pedi 30/50/70/90分别达到100%/100%/87.5%/62.5%和100%/100%/81.9%/45.5%的缓解。两组患儿的不良反应最常见为感染,无严重不良事件发生。结论:托珠单抗与依那西普治疗pJIA疗效确切,托珠单抗能更快降低炎症指标,改善疾病活动度,并可调节亢进的体液免疫及调节CD4+T、CD19+B细胞。     

D-氨基葡糖盐酸盐对小鼠淋巴细胞增生及IL-2产生的作用

目的研究D-氨基葡糖盐酸盐(GAH)对小鼠淋巴细胞增生及IL-2产生的作用。方法用噻唑蓝(MTT)法检测淋巴细胞增生,碘化丙锭(PI)检测淋巴细胞周期,酶联免疫吸附测定(ELISA)法测定细胞内IL-2的含量。结果在200～50μg/mL浓度范围内,GAH能促进小鼠淋巴细胞增生,并可诱导淋巴细胞分泌IL-2。结论GAH能有效的促进淋巴细胞增生,促进分泌IL-2,具有免疫作用。     

Relationship between Geriatric Nutritional Risk Index and total lymphocyte count and mortality of hemodialysis patients

We examined the relationships between Geriatric Nutritional Risk Index (GNRI), total lymphocyte count (TLC), and mortality in hemodialysis (HD) patients. We examined GNRI and TLC in 120 maintenance HD patients and followed these patients for 120 months. Predictors of all‐cause death were examined using life table analysis and the Cox proportional hazards model. TLC marginally correlated with GNRI (r = 0.176; p = 0.090) and significantly with phosphorus levels (r = 0.206; p = 0.026). Life table analysis revealed that subjects with a GNRI < 90 (n = 19) had lower survival rates than did those with a GNRI ≥ 90 (n = 101; Wilcoxon's test, p = 0.048), but subjects with a TLC < 1500/mm³ (n = 76) had similar survival rates compared with subjects with a TLC ≥ 1500/mm³ (n = 44; Wilcoxon's test, p = 0.500). Multivariate Cox proportional hazards analyses demonstrated that GNRI is a significant predictor of mortality (hazard ratio 9.315, 95% confidence interval 1.161–74.753, p = 0.036), after adjusting for age, sex, presence of type 2 diabetes mellitus, Kt/V, normalized protein catabolic rate, hematocrit, phosphorus, systolic blood pressure and TLC. Our findings suggest the TLC may be used as a simple nutritional tool, but may not be a predictor of mortality in HD patients. These findings require confirmation by further studies.     

T Lymphocyte Antigen 4-Modified Dendritic Cell Therapy for Asthmatic Mice Guided by the CCR7 Chemokine Receptor

The CD80/CD86-CD28 axis is a critical pathway for immuno-corrective therapy, and the cytotoxic T lymphocyte antigen 4 (CTLA4) is a promising immunosuppressor targeting the CD80/CD86-CD28 axis; however, its use for asthma therapy needs further optimization. A human CTLA4 fused with the IgCγ Fc (CTLA4Ig) and mouse CC chemokine receptor type7 (CCR7) coding sequences were inserted into a recombinant adenovirus (rAdV) vector to generate rAdV-CTLA4Ig and rAdV-CCR7. The naive dendritic cells (DCs) were infected with these rAdVs to ensure CCR7 and CTLA4Ig expression. The therapeutic effects of modified DCs were evaluated. rAdV-CTLA4Ig and rAdV-CCR7 infected DCs improved all asthma symptoms. Inflammatory cell infiltration and cytokine analysis showed that rAdV-CTLA4Ig and rAdV-CCR7-modified DC therapy reduced the number of eosinophils and lymphocyte and neutrophil infiltration in the lung. Interestingly, assessment of the humoral immunity showed that the IL-4 and IFNγ levels of the rAdV-CTLA4Ig and rAdV-CCR7-modified DC-treated mice decreased significantly and did not reverse the Th1/Th2 balance. DCs expressing CCR7 displayed guidance ability for DC migration, primarily for DCs in the inflammatory lung. Additionally, the rAdVs caused an inflammatory response by inducing DC differentiation, inflammatory cell infiltration and changes in cytokines; however, mice transplanted with rAdV-green fluorescent protein (GFP)-infected DCs displayed no asthma manifestations. In conclusion, CTLA4Ig-modified DCs exhibited a therapeutic effect on asthma, and CCR7 may guide DC homing. The combination of these two molecules may be a model for precision-guided immunotherapy.     

~(60)Coγ射线辐射对淋巴细胞化学发光的生物效应(英文)

用淋巴细胞化学发光(Ly-CL)技术,研究了离体状况下~(60)Coγ射线辐射对PHA或ConA激发的Ly-CL的生物效应。结果表明:(1)0.25Gy~(60)Coγ射线辐射对PHA(200μg/mL)激发的Ly-CL峰值有增强趋势(P>0.05),0.5Gy有明显增强效应(P<0.05),1～16Gy引起显著或非常显著性抑制(P<0.05或P<0.01)。(2)2～16Gy~(60)Coγ射线辐射对ConA(50、100μg/mL)激发的Ly-CL峰值产生显著或非常显著性抑制作用(P<0.05或 P<0.01)。回归分析表明,峰值下降幅度和辐射剂量间有显著线性关系(P<0.0005)。2～16Gy~(60)Coγ射线辐射对PHA或ConA引起的Ly-CL峰时无影响(P>0.05)。     

阿胶对小鼠免疫功能的影响

目的：探讨阿胶对小鼠免疫功能的影响。方法：小鼠连续皮下注射氢化可的松建立免疫机能低下模型,用不同剂量的阿胶灌胃小鼠28d后,分别测定小鼠的免疫器官重量、血清溶血素水平、迟发型变态反应、脾淋巴细胞增殖、腹腔巨噬细胞吞噬能力、血清中细胞因子白介素-3（IL-3）、γ-干扰素（IFN-γ）和白介素-4（IL-4）水平。结果：阿胶能显著升高免疫低下模型小鼠胸腺指数（P〈0.05,P〈0.01）;显著提高小鼠血清溶血素含量（P〈0.01）;显著促进小鼠的迟发型变态反应和脾淋巴细胞的增殖能力（P〈0.05,P〈0.01）;显著升高小鼠腹腔巨噬细胞对鸡红细胞的吞噬率和吞噬指数（P〈0.05,P〈0.01）;显著提高血清中细胞因子IL-3和IFN-γ水平（P〈0.05,P〈0.01）,降低IL-4水平（P〈0.05,P〈0.01）,提高IFN-γ/IL-4的比值（P〈0.01）。结论：阿胶对小鼠特异性及非特异性免疫机能具有显著调节作用。     

大鼠胸腔淋巴结及外周血淋巴细胞染色体畸变与~(60)Coγ射线照射剂量的关系

大鼠经~(60)Coγ射线全身均匀照射后,胸腔淋巴结(TLN)及外周血淋巴细胞的染色体畸变细胞率和总畸变率与受照剂量(0.5—5.0Gy)的关系,可用回归方程 Y=KD_m 表示。虽然 TLN 的畸变细胞率、无着丝粒断片畸变率和总畸变率略高于外周血,TLN 的双着丝粒畸变率又较后者低,但回归系数差异的显著性检验证明,辐射诱发这两种组织染色体畸变的剂量效应关系,差异不显著。本文在各个剂量点上都观察到了染色单体交换(cte),其发生率比受照离体人血高得多。     

~(60)Co-γ线对刀豆球蛋白(ConA)和脂多糖(LPS)诱导的淋巴细胞的效应

应用~3H-TdR掺入法研究ConA和LPS诱导后的淋巴细胞亚群的辐射效应及其相互关系。体外实验说明ConA细胞具有激活LPS对B细胞的诱导作用。当ConA细胞受10Gy照射后~3H-TdR掺入明显下降,并失去激活作用。LPS细胞受照不能被正常ConA细胞所激活。两种细胞受照后混合培养出现ConA细胞对LPS细胞的抑制作用。应用琼脂扩散盒培养法反映辐射对两种细胞的效应更明显。 8例鼻咽癌病人接受一个疗程的~(60)Coγ线治疗后,其ConA细胞的掺入显著下降,失去激活B细胞的作用。LPS细胞不能被正常ConA细胞所激活。本实验提示ConA细胞的放射敏感性比LPS细胞高。     

Sphingosine-1-Phosphate Receptor Type 4 (S1P4) Is Differentially Regulated in Peritoneal B1 B Cells upon TLR4 Stimulation and Facilitates the Egress of Peritoneal B1a B Cells and Subsequent Accumulation of Splenic IRA B Cells under Inflammatory Conditions

Background: Gram-negative infections of the peritoneal cavity result in profound modifications of peritoneal B cell populations and induce the migration of peritoneal B cells to distant secondary lymphoid organs. However, mechanisms controlling the egress of peritoneal B cells from the peritoneal cavity and their subsequent trafficking remain incompletely understood. Sphingosine-1-phosphate (S1P)-mediated signaling controls migratory processes in numerous immune cells. The present work investigates the role of S1P-mediated signaling in peritoneal B cell trafficking under inflammatory conditions. Methods: Differential S1P receptor expression after peritoneal B cell activation was assessed semi‑quantitatively using RT-PCR in vitro. The functional implications of differential S1P₁ and S1P₄ expression were assessed by transwell migration in vitro, by adoptive peritoneal B cell transfer in a model of sterile lipopolysaccharide (LPS)‑induced peritonitis and in the polymicrobial colon ascendens stent peritonitis (CASP) model. Results: The two sphingosine-1-phosphate receptors (S1PRs) expressed in peritoneal B cell subsets S1P₁ and S1P₄ are differentially regulated upon stimulation with the TLR4 agonist LPS, but not upon PMA/ionomycin or B cell receptor (BCR) crosslinking. S1P₄ deficiency affects both the trafficking of activated peritoneal B cells to secondary lymphoid organs and the positioning of these cells within the functional compartments of the targeted organ. S1P₄ deficiency in LPS-activated peritoneal B cells results in significantly reduced numbers of splenic innate response activator B cells. Conclusions: The S1P-S1PR system is implicated in the trafficking of LPS-activated peritoneal B cells. Given the protective role of peritoneal B1a B cells in peritoneal sepsis, further experiments to investigate the impact of S1P₄-mediated signaling on the severity and mortality of peritoneal sepsis are warranted.