Pyroptosis: A road to next-generation cancer immunotherapy

The goal of cancer immunotherapy is to clear tumor cells by activating antitumor immunity, especially by mobilizing tumor-reactive CD8⁺T cells. Pyroptosis, programmed lytic cell death mediated by gasdermin (GSDM), results in the release of cellular antigens, damage-associated molecular patterns (DAMPs) and cytokines. Therefore, pyroptotic tumor cell-derived tumor antigens and DAMPs not only reverse immunosuppression of the tumor microenvironment (TME) but also enhance tumor antigen presentation by dendritic cells, leading to robust antitumor immunity. Exploring nanoparticles and other approaches to spatiotemporally control tumor pyroptosis by regulating gasdermin expression and activation is promising for next-generation immunotherapy.     

Comparison of the efficacy and safety of the adalimumab biosimilar TQ-Z2301 and adalimumab for the treatment of Chinese patients with active ankylosing spondylitis: a multi-center,randomized, double-blind,phase III clinical trial

Clinical Rheumatology - To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing...     

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials

BackgroundRandomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups.MethodsA systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.ResultsData from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference ?6.97 days). Outcomes remained stable in the high-risk subgroups.ConclusionLPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.     

Atrial performance in healthy subjects following high altitude exposure at 4100 m: 2D speckle-tracking strain analysis

The International Journal of Cardiovascular Imaging - High altitude (HA) exposure has been considered as a cardiac stress and might impair ventricular diastolic function. Atrial contraction is...     

普拉梭菌干预对溃疡性结肠炎小鼠免疫应答、肠道菌群、肠黏膜屏障的影响

目的:研究普拉梭菌干预对溃疡性结肠炎(UC)小鼠免疫应答、肠道菌群、肠黏膜屏障的影响。方法:C57BL/6J小鼠随机分为对照组、UC组、普拉梭菌组,后2组采用三硝基苯磺酸灌肠的方法建立UC模型,普拉梭菌组给予普拉梭菌的菌液灌胃干预。干预7d天后,比较3组间免疫应答、肠道菌群、肠黏膜屏障的差异。结果:UC组血清中白介素-10(IL-10)、转化生长因子-β1(TGF-β1)的含量及肠黏膜中叉头框P3(Foxp3)、闭锁小带蛋白-1(ZO-1)、闭锁蛋白(occludin)、密封蛋白-1(claudin-1)、密封蛋白-2(claudin-2)的表达量及粪便中双歧杆菌、乳酸杆菌的数目明显低于对照组,血清中白介素-17(IL-17)、二胺氧化酶(DAO)、D-乳酸(D-LA)的含量及肠黏膜中视黄酸相关孤儿核受体γt(RORγt)的表达量及粪便中肠杆菌、肠球菌的数目明显高于对照组(P<0.05);普拉梭菌组血清中IL-10、TGF-β1的含量及肠黏膜中Foxp3、ZO-1、occludin、claudin-1、claudin-2的表达量及粪便中双歧杆菌、乳酸杆菌的数目明显高于UC组,血清中IL-17、DAO、D-LA的含量及肠黏膜中RORγt的表达量及粪便中肠杆菌、肠球菌的数目明显低于UC组(P<0.05)。结论:普拉梭菌用于UC小鼠的干预能够改善Th17/Treg免疫应答、肠道菌群及肠黏膜屏障。     

Risk-based,response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.     

我国7个地理区域哮喘急性发作住院患者季节性分布特征

目的 了解我国7个地理区域内哮喘急性发作住院患者的季节性分布特征。方法 对全国7个地理区域（东北、华北、华中、华东、华南、西北、西南）内的29家三甲医院2013－2014年间因哮喘急性发作住院的患者例数及同期该院呼吸内科总住院患者例数进行统计,逐月计算因哮喘急性发作住院患者占总住院患者的比例。对各个地区之间及每个地区不同月份之间哮喘急性发作患者的住院情况进行了统计学分析。结果 在研究的时间范围内,29家医院的呼吸科总住院患者为206 135例次,其中因哮喘急性发作住院患者为6 480例次,占同期总住院数的3.14%。不同地区间因哮喘急性发作住院人数占同期总住院人数的比例差异较大,东北地区比例最高（5.61%）,华东地区比例最低（1.97%）。不同地区之间哮喘患者住院比例的差异均有统计学意义（P<0.000 1）。多数地区因哮喘急性发作住院患者例数及比例都有两个高峰,分别位于2－4月及9－10月,东北、华东及华南地区的春季高峰更为显著,而华北及西南地区的秋季高峰更为明显,西北地区的高峰则位于冬季（12－1月）及夏季（6－8月）。东北、华北及西南地区各月份之间哮喘急性发作住院情况的差异有统计学意义（P<0.005）。结论 不同地区哮喘急性发作住院患者存在一定的季节波动性,多数地区存在春季及秋季两个高峰。     

结直肠癌组织中DDX5表达水平及其与患者预后的相关性

目的:探讨RNA解螺旋酶DDX5(p68)在结直肠癌（colorectal cancer,CRC）组织中的表达水平及其与结直肠癌患者预后的相关性。方法:选取2015年03月至2016年11月陆军军医大学第二附属医院收治的接受外科手术初治的213例结直肠癌患者,收集其临床资料、肿瘤组织石蜡标本;采用免疫组化方法检测肿瘤组织中DDX5蛋白表达情况;随访3年,分析DDX5蛋白表达水平与结直肠癌患者预后的关系。结果:截止2019年11月30日,共有202例患者完成随访;死亡23例,复发44例,共计67例,预后不良率为33.17%;预后不良组在肿瘤分化程度上低于预后良好组,淋巴结转移情况、肿瘤浸润型比例、临床分期上高于预后良好组,差异具有统计学意义（P＜0.05）;预后不良组肿瘤组织中DDX5蛋白表达水平高于预后良好组,差异具有统计学意义（P＜0.05）;以DDX5表达水平中位数为截点,DDX5高表达组3年无进展生存率为58.88%,低于DDX5低表达组的78.30%,DDX5高表达组疾病进展风险显著高于DDX5低表达组（P=0.002）;多因素Logistic分析显示,肿瘤低分化（OR=14.097）、淋巴结N1-2转移（OR=118.602）、高临床分期（OR=1 525.596）、浸润型生长（OR=2.533）及DDX5高表达（OR=8.958）是影响结直肠癌患者预后不良的独立危险因素（P＜0.05）。结论:结直肠癌组织中DDX5蛋白高表达可导致患者预后不良,可能是评估结直肠癌预后的一项生物标志物。