甲状腺疾病患者血清 Tg-CIC 中 Tg-Ab 水平检测及相关临床研究

目的　对血清甲状腺球蛋白免疫复合物 (thyroglobulin circulating immune complex, Tg-CIC) 中抗甲状腺球蛋白抗体 (anti-thyroglobulin antibody, Tg-Ab) 含量检测，探讨 Tg-CIC 在甲状腺疾病中的临床以及流行病学意义。方法　收集甲状腺疾病患者血清标本 187 例，每例血清标本分为两组 ( 实验组和空白对照组 )，采用免疫复合物解离专利技术对甲状腺疾病患者血清标本 Tg-CIC 进行分离、解离，通过检测 Tg-CIC 解离后的 Tg-Ab 含量来间接反映甲状腺疾病患者血清中Tg-CIC 水平，按照不同的甲状腺疾病进行分组并对实验结果分析讨论。结果　不同甲状腺患者血清中 Tg-CIC 总阳性率达 92.51%，不同甲状腺疾病血清中 Tg-CIC 的阳性率差异无统计学意义 (χ?=2.917, P>0.05)。不同甲状腺疾病患者间血清游离 Tg-Ab 含量差异无统计学意义 (H=3.882, P>0.05)，不同甲状腺疾病患者间血清 CIC 中 Tg-Ab 含量差异无统计学意义(H=5.5842, P>0.05)。不同甲状腺疾病患者中，甲状腺功能亢进、甲状腺炎以及甲状腺结节患者血清游离 Tg-Ab 的含量与血清 CIC 中的 Tg-Ab 含量呈正相关 (P<0.05)，甲状腺功能减退、甲状腺肿瘤患者血清游离 Tg-Ab 的含量与血清 CIC 中的Tg-Ab 含量不相关 (P>0.05)。结论　在甲状腺疾病患者血清中，大部分可检出 Tg-CIC，与疾病类型无关。而甲状腺疾病患者中，甲状腺功能亢进、甲状腺炎以及甲状腺结节患者血清游离 Tg-Ab 含量与血清 CIC 中 Tg-Ab 含量存在相关性，为我们进一步了解 Tg-CIC 与甲状腺疾病的发生、发展的相关性研究奠定了基础，提供了新的研究视角。     

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

柴芍四金汤预防ERCP术后胆总管结石复发的临床观察

目的 研究柴芍四金汤预防ERCP术后胆总管结石复发的临床疗效。方法 选取昆山市中医医院脾胃肝胆科2014年1月至2016年12月因胆总管结石行ERCP取石病例120例，按随机数字表法将120例病例随机分为治疗组和对照组，每组各60例，治疗组口服自拟柴芍四金汤，每日1剂，水煎400 mL，分早晚两次温服，随证加减；对照组口服熊去氧胆酸250 mg/次，3次/d，2组均连续药物治疗6月，观察术后2周血清中总胆红素（Tbil）、直接胆红素（Dbil）、碱性磷酸酶（ALP）、谷氨酰转肽酶（GGT）指标、术后半年临床症状（包括腹痛、腹胀、恶心、纳差）及术后6月、12月、18月胆总管结石复发情况。结果 治疗组术后6月、12月及18月结石复发率略低于对照组，但两者差异无统计学意义（ P >0.05）；治疗组在改善腹痛、腹胀、恶心、纳差症状方面优于对照组（ P <0.05）；治疗组在改善血清Tbil、Dbil、ALP、GGT水平方面优于对照组（ P <0.01）。结论 柴芍四金汤能有效预防ERCP术后胆总管结石的复发，且能改善胆总管结石引起的临床症状及血清生化指标。      

淫羊藿、巴戟天中药提取物对恒河猴M0、M1型单核衍生巨噬细胞基因表达的影响

【目的】探讨中药淫羊藿、巴戟天提取物(中药注射液喘可治的组成)对恒河猴单核衍生的巨噬细胞在未极化(M0)、M1极化条件下基因表达的影响,分析其可能的免疫调节的作用机制。【方法】采用密度梯度离心法分离中国恒河猴外周血单个核细胞(PBMCs),采用贴壁法纯化出单核细胞,并以粒细胞巨噬细胞集落刺激因子(GM-CSF)刺激5 d以使单核细胞分化成巨噬细胞;然后不加入极化因子(M0)或以干扰素γ(IFN-γ,继续培养2 d)诱导巨噬细胞极化为M1表型,同时分别加入淫羊藿、巴戟天提取物进行干预;然后提取m RNA并逆转录后,采用实时荧光定量PCR检测CCR5、CD4、CTLA-4、Fox P3、IDO、IL-10、TGF-β等基因表达量。【结果】与空白对照组比较,加入巴戟天提取物培养的M0巨噬细胞基因表达上调不明显;经淫羊藿提取物培养的M0巨噬细胞,CCR5基因表达量上调4.21倍,TGF-β上调7.66倍,Fox P3、IL-10轻度上调,而CD4、CTLA-4、IDO等基因表达改变倍数无明显变化。经巴戟天提取物刺激的M1型巨噬细胞,CTLA-4基因表达量上调3.22倍,Fox P3上调3.69倍,CCR5、CD4、IL-10、IDO基因改变倍数均无明显变化,TGF-β未测出;而由淫羊藿提取物刺激的M1型巨噬细胞,IL-10的表达量上调11.83倍,Fox P3上调4.55倍,IDO、CCR5、CD4、CTLA-4基因改变倍数无明显变化,TGF-β未测出。【结论】巴戟天和淫羊藿提取物培养能够上调M1型巨噬细胞IL-10、Fox P3、CTLA-4等抑炎基因表达,淫羊藿提取物能够上调M0巨噬细胞CCR5和TGF-β等基因表达,促进病原体清除和组织修复,从而发挥多效免疫调节作用。     

不同波形低频率电刺激对小鼠海马电点燃癫痫的作用比较

目的观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法采用电点燃刺激法建立小鼠癫痫模型, 观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响, 并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果与对照组比较, 正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级(2.85 ± 0.27 vs 4.75 ±0.12, P < 0.05)、减少大发作概率(53.6% vs 96.5%, P < 0.01) 和缩短后放电持续时间[(16.22 ± 1.69) s vs (30.29 ± 1.12) s, P < 0.01], 而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级(3.58 ± 0.16, P < 0.05)、减少大发作概率(66.7%, P < 0.01);但对海马后放电持续时间及大发作持续时间无影响(均 P>0.05)。此外, 电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用( P < 0.05或 P < 0.01), 而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。 结论低频率电刺激抗癫痫作用受波形参数的影响, 其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。     

Clinical analysis of high-intensity focussed ultrasound ablation for abdominal wall endometriosis: a 4-year experience at a specialty gynecological institution

Objective: To evaluate the long-term clinical effect of high-intensity focussed ultrasound (HIFU) as a non-invasive modality for ablation of abdominal wall endometriosis (AWE) foci.

Methods: All women who were diagnosed with cutaneous endometriosis and underwent HIFU ablation and 4-year follow-up were included. Patient symptoms, imaging performed, HIFU ablation, recurrence, lesion location, size and number were collected and analyzed.

Results: A total of 51 women with 57 painful abdominal wall masses with a median volume of 4.00?cm³ and a mean age of 30.5±2.12 years were treated with HIFU. The main symptoms were a palpable painful abdominal mass (93%), protrusion of the skin (28.1%, 16) or lack of protrusion of the skin (71.9%, 41). Ultrasound was initially performed in 100% (51) of women, whereas 6% (3) required MRI examinations to distinguish the features and range of the masses. Ablation was performed with a median 300?s of sonication time, 40?min treatment time, 150?W of power and 41800?J of total energy to treat lesions that were a median volume of 3.83?cm³. No severe complications occurred, except in one patient with a first-degree skin burn, during the 48-month follow-up period. The pooled recurrence of cutaneous endometriosis occurred in 3.9% (2) of women.

Conclusion: The diagnosis of AWE should be confirmed with imaging of the lesion number, location, size and features before HIFU ablation. HIFU should be the first choice for the treatment of AWE as it is a non-invasive method, with high efficiency and safety and rapid postoperative recovery.