Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.     

冠状病毒肺炎细胞因子风暴及免疫调控治疗

细胞因子风暴是一种失控的过度免疫应答,是冠状病毒肺炎的重要发病机制。病毒劫持机体的免疫系统,导致免疫调节的负反馈丧失、多种细胞因子异常升高,损害了肺泡弥散功能并造成多器官功能障碍。靶向冠状病毒细胞因子风暴的特异性治疗研究,如粒细胞集落刺激因子、托珠单抗、卡莫他特、血液净化治疗等已取得系列成果,其可能是缓解新型冠状病毒肺炎（COVID-19）疫情的有效手段。但COVID-19具有独特的病理特征,上述治疗的研究成果仍需进一步临床试验来验证。本文就冠状病毒肺炎细胞因子风暴及免疫调控治疗进展进行综述。     

卵清蛋白致敏SD大鼠上下呼吸道炎症反应动物模型的构建

目的：以卵清蛋白为致敏原,建立具有变应性鼻炎和变应性哮喘为主要特征的大鼠模型,观察大鼠模型上下呼吸道炎症反应及病理改变。方法：采用6-8周雄性SD大鼠,随机分为变应性鼻炎组10只,变应性鼻炎对照组10只,变应性哮喘组10只,变应性哮喘对照组10只,以卵清蛋白致敏并激发制成变应性鼻炎和变应性哮喘模型。HE染色和甲苯胺蓝染色分别检测变应性鼻炎模型和变应性哮喘模型鼻黏膜及肺组织中EOS、MC的表达。结果：变应性鼻炎组、变应性哮喘组大鼠卵清蛋白激发后出现了典型的变应性鼻炎、变应性哮喘症状（评分〉5分）,鼻黏膜和肺组织可见较多的嗜酸粒细胞和肥大细胞浸润,且两组鼻黏膜和肺组织中EOS、MC数明显多于相应对照组（P〈0．05）。结论：卵清蛋白致敏SD大鼠能够成功建立变应性鼻炎和变应性哮喘动物模型,有望为上、下呼吸道炎症反应的诊断、治疗及研究工作提供有效方法及组织形态学依据。     

人重组粒细胞集落刺激因子治疗大鼠缺血性脑梗死的实验研究

目的 探讨人重组粒细胞集落刺激因子(rhG-CSF)对大鼠缺血性脑梗死的治疗作用及其应用的时间窗.方法 采用线栓法制作大鼠缺血性脑梗死模型,分别于梗死后1h、6h给予皮下注射rhG-CSF(50 μg/kg);对照组给予同等剂量的生理盐水皮下注射.TTC染色检测梗死体积.结果 术后48h处死大鼠,梗死后1h给药,治疗组与对照组梗死体积分别为(135.0±13.8)mm3、(230.0±57.8)mm3,两者比较P＜0.001;梗死后6h给药,梗死体积分别为(140.0±25.3)mm3、(240.0±30.6)mm3,两者比较P＜0.001.结论 rhG-CSF可减轻大鼠缺血性脑梗死程度,减小梗死体积.术后6h给药与术后1h给药具有相当的疗效.     

rhG-CSF拮抗糖尿病脑缺血后神经细胞凋亡的研究

目的验证重组人粒细胞集落刺激因子(rhG-CSF)是否能改善局灶性脑缺血糖尿病大鼠的神经功能,并观察对神经细胞凋亡的影响。方法线栓法复制糖尿病大鼠大脑中动脉栓塞模型,rhG-CSF干预组连续皮下注射rhG-CSF,50μg·kg-1·d-1,进行神经功能缺损评分,采用TUNEL染色计数脑缺血周边区神经细胞凋亡数。结果rhG-CSF干预组神经功能缺损评分明显低于对照组(P<0.01);rhG-CSF干预组缺血周边区的TUNEL阳性细胞数均明显少于对照组(P<0.01)。结论rhG-CSF可拮抗糖尿病脑缺血之后神经细胞凋亡,改善神经功能。     

预激方案治疗难治急性髓系白血病的临床观察

目的探讨预激方案治疗难治急性髓系白血病的临床疗效和毒副作用。方法选择2004年7月-2005年11月在该科治疗的难治急性髓系白血病17例,2例为骨髓增生减低者,1例为71岁患者伴冠心病,用预激方案前未经化疗。其余14例经过传统的MA、HA、DA等方案治疗1疗程,未取得完全缓解,造血恢复后仍体质差,全血细胞减少。预激方案ACR10-14mg/m^2,Qd,第1-8天,Ara-c 10mg/m^2,Q12h,第1-14天,G-CSF200μg/m^2,Qd,第1-14天。结果17例经上述治疗达CR11例（64.7%）,PR3例（17.6%）,NR3例（17.7%）。结论预激方案治疗急性髓系白血病完全缓解率与传统的的HA、DA方案相似,但不良反应小、使用安全,为老年、低增生性及体质差的急性髓系白血病患者提供了新的治疗方案。     

脑梗死患者急性期C反应蛋白、细胞因子及外周血白细胞和中性粒细胞的变化

目的观察脑梗死（CI）急性期血清超敏C反应蛋白（hs-CRP）、IL-6、IL-18、及外周血白细胞总数、中性粒细胞百分比变化。方法对182例脑梗死患者分别抽静脉血统计白细胞总数、中性粒细胞百分比,测定血清hs-CRP、IL-6、IL-18的含量。结果脑梗死组白细胞总数、中性粒细胞百分比显著增高（P〈0.01）,hs-CRP、IL-6、IL-18水平明显高于健康组（P〈0.01）。结论测定急性脑梗阻死患者血清hs-CRP、IL-6、IL-18并观察外周血白细胞的变化,对急性脑梗死患者有较好的诊断价值,是评估治疗、病性轻重的很好指标。     

Effect of granulocyte macrophage colony-stimulating factor in a patient with benign systemic mastocytosis

We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GM-CSF), a known inhibitor of in vitro mast cell differentiation, in a patient with benign, adult-onset systemic mastocytosis. In vitro effects of GM-CSF on bone marrow cultures before the start of treatment showed a marked inhibition of mast cell marker expression [tryptase, Kit, and high-affinity IgE receptor (FcepsilonRIalpha)] at both protein and mRNA levels. Therefore, the patient was treated with daily injections of GM-CSF for 10 weeks. After an initial improvement, increasing worsening of clinical symptoms was noted, and the patient refused further treatment. Lesional skin biopsies showed an increase of toluidine blue-positive mast cells, compared with uninvolved skin, with further significant increase after treatment. Similar results were obtained on staining for mast cell-specific tryptase and Kit, as well as for CD1a and FcepsilonRIalpha. These findings show that GM-CSF inhibits human bone marrow mast cell differentiation in vitro, and also in mastocytosis. However, GM-CSF apparently enhances recruitment of mast cell as well as dendritic cell precursors into the tissue during systemic treatment. These findings and the observed adverse clinical effects in the present patient make it unlikely that GM-CSF monotherapy will be beneficial for the treatment of mastocytosis.     

A randomized comparison of once versus twice daily recombinant human granulocyte colony-stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation

To evaluate the schedule dependency of granulocyte colony-stimulating factor (G-CSF) (filgrastim) for stem cell mobilization, we conducted a randomized comparison in 50 healthy donors, with one subcutaneous daily injection of 10 microg/kg G-CSF (n = 25) compared with twice injections daily of 5 microg/kg G-CSF (n = 25). The two groups were well balanced for age, body weight and sex. G-CSF application was performed on an out-patient basis and leukapheresis was started in all donors on day 5. The most frequent side-effects of G-CSF were mild to moderate bone pain (88%), mild headache (72%), mild fatigue (48-60%) and nausea (8%) without differences between the two groups. The CD34(+) cell count in the first apheresis was 5.4 x 10(6)/kg donor weight (range 2.8-13.3) in the 2 x 5 microg/kg group compared with 4.0 x 10(6)/kg (range 0.4-8.8) in the 1 x 10 microg/kg group (P = 0.007). The target of collecting > 3.0 x 10(6) CD34(+) cells/kg donor weight with one apheresis procedure was achieved in 24/25 (96%) donors in the 2 x 5 microg/kg group and in 17/25 (68%) donors in the 1 x 10 microg/kg group. The target of collecting > 5.0 x 10(6) CD34(+) cells/kg in the first apheresis was achieved in 64% in the 2 x 5 microg/kg group, but in only 36% in the 1 x 10 microg/kg group. The progenitor cell assay for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) was higher in the 2 x 5 microg/kg group than in the 1 x 10 microg/kg group (7.0 vs. 3.5 x 10(5)/kg, P = 0.01; 6.6 vs. 5.0 x 10(5)/kg; P = 0.1). Administering G-CSF (filgrastim) at a dosage of 5 microg/kg twice daily rather than 10 microg/kg once daily is recommended; this leads to a higher CD34(+) cell yield and requires fewer apheresis procedures without increasing toxicity or cost.     

ANTI-ALLERGIC EFFECTS OF SANGUISORBA OFFICINALIS ON ANIMAL MODELS OF ALLERGIC REACTIONS

ABSTRACT

We investigated the effect of aqueous extract of Sanguisorba officinalis L.(Rosaceae) root (SOAE) on the immediate-type allergic reactions in vivo and in vitro. SOAE (0.01 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. When SOAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SOAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE. SOAE (0.001 to 1 mg/mL) also dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP (cAMP) in RPMC, When SOAE was added, significantly increased compared with that of normal control. Moreover, SOAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α (TNF-α) production. These results suggest that SOAE may be beneficial in the regulation of immediate-type allergic reaction.