芫根调节免疫功能的小肠转录组学研究

利用生物信息学技术初步探索芫根调控肠道免疫功能的分子生物学机制。方法 选择雄性SPF级BALB/c小鼠18只，随机分为3组，每组6只。SC1组小鼠每只每次灌胃芫根提取液150 μL，SC2组小鼠每只每次灌胃绞碎芫根原浆悬液150 μL，NC组小鼠每只每次灌胃生理盐水150 μL，连续7 d每日灌胃一次。分别取每组小鼠小肠组织样品提取RNA，总RNA的质检合格后，进行转录组测序。按GO功能和KEGG信号通路对差异表达基因聚类分析揭示差异表达高度富集的免疫相关通路。从免疫角度分析芫根灌胃小鼠小肠组织的基因表达变化情况。结果 转录组测序共检测到27733条 mRNA的表达，SC1组与NC组比较，显著差异表达基因1635个，其中上调差异表达基因1236个，下调差异表达基因399个；SC2组与NC组比较，显著差异表达基因2872个，其中上调差异表达基因2233个，下调差异表达基因639个（P＜0.05）。按GO功能和KEGG信号通路聚类分析显示差异表达基因在白介素分泌、干扰素反应、T细胞受体信号通路及维生素和脂肪消化吸收等途径的富集度在两个芫根组中均居于前20位（P＜0.01），肠黏膜趋化因子CCL20和巨噬细胞极化标志物CD274等免疫蛋白编码基因差异表达显著且同属于上述多个免疫通路。结论 芫根灌胃小鼠小肠的差异表达基因在白介素分泌、干扰素反应、T细胞受体信号通路、营养物质消化吸收等途径高度富集，提示芫根对肠道免疫系统及肠黏膜功能的调节，其中CD274的表达上调和CCL20的表达下调提示诱导M1型巨噬细胞极化和T细胞活化可能是芫根调控免疫和维护肠道正常结构功能的重要途径。     

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

1. Download : Download high-res image (268KB)
2. Download : Download full-size image

     

免疫抑制儿童感染新型冠状病毒Omicron变异株病毒清除时间的回顾性队列研究

背景：儿童新型冠状（新冠）病毒Omicron变异株流行期间，免疫抑制状态儿童新冠病毒清除时间定量分析研究较少。 目的：探讨新冠病毒Omicron株感染后免疫抑制和非免疫抑制儿童病毒清除的时间差别，为公共卫生政策制定和精准疫情防控措施提供临床数据。 设计：回顾性队列研究。 方法：以新冠病毒Omicron变异株感染住院患儿为队列人群，分为免疫抑制组和非免疫抑制组，免疫抑制分为绝对免疫抑制、相对免疫抑制和实施免疫抑制疗法，以免疫抑制组病例的性别、年龄和新冠病毒感染的分型与非免疫抑制组行1∶3匹配。以鼻咽拭子新冠病毒PCR检测拷贝数阈（Ct）值≥35为队列终点。 主要结局指标：新冠病毒清除时间。 结果：2022年4月12日至2022年5月12日在上海市新冠病毒感染定点收治医院符合本文共同纳入和排除标准的连续病例728例。免疫抑制组33例，其中绝对免疫抑制8例，相对免疫抑制23例，接受免疫抑制疗法2例（不包括绝对和相对免疫抑制患儿）。非免疫抑制组匹配后99例。2组临床症状、新冠病毒感染治疗和疫苗接种次数差异均无统计学意义。免疫抑制组和非免疫抑制组新冠病毒清除时间分别为（16.5±6.8）和（10.3±4.4）d，差异有统计学意义。免疫抑制组和非免疫抑制组新冠病毒感染轻型病例病毒清除时间分别为（14.0 ± 8.3）和（9.7 ± 3.1）d，普通型病例病毒清除时间分别为（18.3 ± 4.9）和（11.2 ± 5.9）d，差异均有统计学意义。2组单日病毒清除率在第9~14天时差异有统计学意义（P为0.005~0.039）。2组普通型病例单日病毒清除率在第10~15天时差异有统计学意义。免疫抑制组新冠病毒感染2周后核酸检测再次呈阳性3例（9%），临床分型均较前轻，3例均未接种新冠疫苗。 结论：Omicron株感染的免疫抑制患儿病毒清除时间较非免疫抑制患儿显著延长，主要反映在第9~14天，免疫抑制患儿病毒复阳风险高，提示需要更长的隔离时间和转阴后严格的病毒监测。     

Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy

1. Download : Download high-res image (235KB)
2. Download : Download full-size image

     

小剂量克赛联合百令胶囊对微小病变型NS的疗效

目的 探讨小剂量克赛联合百令胶囊对微小病变型肾病综合征（NS）患者高凝血状态和免疫功能的影响。 方法 选取2017年4月～2020年5月于本院就诊的90例微小病变型NS患者，按随机数表法分为观察组（45例）和对照组（45例）。对照组服用百令胶囊，观察组同时应用小剂量克赛。观察两组患者临床疗效、肾功能指标变化、凝血指标变化、血液流变学指标变化、T淋巴细胞亚群及药物不良反应。 结果 治疗后，观察组治疗总有效率高于对照组（P＜0.05）；观察组肾功能损伤指标及24 h尿蛋白水平均低于对照组（P＜0.05）；观察组凝血相关时间指标水平高于对照组，凝血相关因子水平低于对照组（P＜0.05）；观察组血液流变学指标水平低于对照组（P＜0.05）；观察组外周T淋巴细胞亚群检测结果显示CD3+、CD4+、CD4+/CD8+水平高于对照组，CD8+水平低于对照组（均P＜0.05）；两组不良反应发生率比较，差异无统计学意义（P＞0.05）。 结论 小剂量克赛联合百令胶囊对微小病变型肾病综合征患者疗效确切，可减少患者肾功能损伤，调节血液高凝状态，降低血液粘稠度，提升人体免疫功能，且安全性较好。