IL-37b作用于树突状细胞CD39/ATP轴抑制类风湿性关节炎大鼠炎症反应的作用及机制

目的探讨白细胞介素37b重组蛋白(rmIL-37b)通过调节CD39/ATP轴抑制树突状细胞(DC)诱导类风湿性关节炎(RA)大鼠炎症反应的机制。方法将SD大鼠随机分为空白对照组(CTL)、CIA模型组、rmIL-37b 5μg/kg组、rmIL-37b 10μg/kg组,每组各10只。除了空白对照组外,其余大鼠采用含有卡介苗的完全弗氏佐剂和牛Ⅱ型胶原混合乳液免疫刺激,建立CIA模型。确定建模成功当天(D0),rmIL-37b组分别尾静脉注射5μg/kg、10μg/kg rmIL-37b;CTL组和CIA模型组注射相同体积的(1 ml/kg)生理盐水,连续给药15 d。免疫组化法检测滑膜组织Nod样受体蛋白3(NRPL3)炎症小体的表达,流式细胞术检测DC表型,另外试剂盒检测血清三磷酸腺苷(ATP)和免疫学指标。结果与CIA模型组相比,rmIL-37b 10μg/kg组大鼠足容积、AI值、NLRP3炎症小体表达量、血清ATP、IL-1β、IL-18、肿瘤坏死因子α(TNF-α)、抗Ⅱ型胶原抗体亚型(anti-ColⅡ-IgG、anti-ColⅡ-IgG2a)水平均降低,同时DC表面CD...     

黄芩素调控 NLRP3 / Caspase-1 通路对牙周炎大鼠牙槽骨吸收的影响

目的 探索黄芩素调控核苷酸结合寡聚化结构域样受体蛋白 3 ( nucleotide-binding oligomerization domain-like receptor protein 3, NLRP3) / 半胱氨酸天冬氨酸蛋白酶 1 ( cysteine aspartate protease 1, Caspase1) 通路对牙周炎大鼠牙槽骨吸收的影响。 方法 将 40 只牙周炎大鼠随机分为模型组、 黄芩素组、 激活剂 组、 黄芩素 + 激活剂组, 另取 10 只正常作为对照组。 检测大鼠釉牙骨质界到牙槽嵴顶 (CEJ-AC) 的距离、 血清中白细胞介素-6 (IL-6)、 转化生长因子-β (TGF-β) 含量以及牙周组织病理变化、 IL-6、 TGF-β 阳性 表达和 NLRP3、 Caspase-1 蛋白表达。 结果 模型组大鼠 CEJ-AC、 NLRP3、 Caspase-1、 IL-6、 TGF-β 水平及 阳性表达水平以及蛋白表达水平均升高 (P< 0. 05); 经黄芩素干预后, 各项指标均降低 (P< 0. 05); 引入 激活剂明显削弱了黄芩素对牙周炎大鼠的抗炎作用。 结论 黄芩素通过抑制 NLRP3 / Caspase-1 通路减轻炎性反应, 控制牙槽骨吸收。     

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.     

基于合作对象探讨我国学术期刊专题/专栏建设

【目的】 了解学术期刊专题/专栏建设的现状,以切实发挥学术期刊专题/专栏建设的作用,为期刊的品牌建设、学术创新、影响力提升和办刊质量提高提供策略。【方法】 采用问卷调查法,对全国范围内397名专题/专栏合作对象(包括期刊主编、编委、审稿人、作者)进行调查,了解他们对期刊专题/专栏建设的态度和意见,从合作对象视角探讨影响学术期刊专题/专栏建设成功率和有效性的因素。【结果】 合作对象态度上,表示支持专题/专栏建设工作的比例较高(71.28%),但供稿率不高(43.37%),存在态度和行为分离的现象。排名前5的供稿率影响因素是期刊被本专业领域研究者认可、期刊被数据库收录情况、期刊影响力、期刊品牌、期刊的处理速度。最优的约稿方式是行业内的学术带头人联系约稿,其次是熟识的专家委托和期刊主编亲自联系进行约稿。合作对象最希望获得的帮助是稿件快速审理发表和确定选题方向。【结论】 为提高学术期刊专题/专栏建设质量,应进一步挖掘重要合作对象的作用,有针对性地选择高供稿率的合作对象;努力挖掘和利用影响合作对象供稿的因素,在期刊品牌建设、扩大影响力方面下功夫;优化约稿方式方法,重视行业学术带头人的作用;同时通过稿件快速审理发表、帮助确定选题并提供发表后推广等服务,提高合作对象对专题/专栏建设工作的认可度和参与度。     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

半夏泻心汤对DSS诱导的溃疡性结肠炎小鼠肠道微生态及Th17/Treg细胞平衡的影响＊

目的 观察半夏泻心汤对饮用葡聚糖硫酸钠（DSS）诱导建立的溃疡性结肠炎（UC）模型小鼠Th17/Treg细胞平衡及肠道微生态的影响，从免疫失衡及菌群紊乱角度分析半夏泻心汤治疗UC的作用机制。方法 将40只C57BL/6J雄性小鼠随机分为空白组、模型组、阳性药（美沙拉嗪）组及半夏泻心汤组，除空白组外的各小鼠采用2.5% DSS水溶液自由饮用7天诱导建立UC小鼠模型。自实验第8日起，分别采用灭菌水、美沙拉嗪水溶液、半夏泻心汤水溶液给上述各组别小鼠灌胃。采用HE染色观察结肠组织病理学变化，ELISA方法检测组织炎症因子含量，流式细胞术检测Th17及Treg细胞的相对数量，16S rRNA测序技术进一步检测模型小鼠粪便中菌群的变化。结果 与空白组比较，模型组小鼠结肠损伤严重，血清炎症因子含量显著升高（P<0.01）；与模型组比较，中药干预组小鼠结肠损伤减轻，血清TNF-α、IFN-γ含量显著下降（P<0.05）。较空白组小鼠相比，模型组小鼠Th17细胞百分比显著升高（P<0.01），而Treg细胞百分比显著降低（P<0.01）。经半夏泻心汤干预后，其小鼠Th17细胞数量均显著降低（P<0.05），Treg细胞数量则显著升高（P<0.05）。同时，半夏泻心汤可升高门水平上Firmicutes、属水平上Lachnospiraceae_NK4A136_group、unclassified_f_Lachnospiraceae、Prevotellaceae_UCG-001、Alistipes；降低门水平上Actinobacteriota，科水平上Bifidobacteriaceae、Atopobiaceae、Clostridiaceae，属水平上Clostridium_sensu_stricto_1、Coriobacteriaceae_UCG-002、Bifidobacterium的相对丰度。结论 半夏泻心汤可使Treg细胞相对数量升高、Th17细胞相对数量降低，以维持Th17/Treg细胞动态平衡；同时可降低有害菌Clostridium_sensu_stricto_1、Coriobacteriaceae_UCG-002的相对丰度，升高产短链脂肪酸类菌Lachnospiraceae_NK4A136_group、Prevotellaceae_UCG-001、unclassified_f_Lachnospiraceae等菌属的相对丰度，调控肠道微生物结构及动态平衡，从而发挥治疗UC的作用。     

Cortical activation by a salient sound modulates visual temporal order judgments: An electrophysiological study of multisensory attentional processes

Previous event-related potential (ERP) studies show that a salient lateral sound activates the visual cortex more strongly contralateral to the sound, observed as an auditory-evoked contralateral occipital positivity (ACOP). Studies showed that this activation enhances the early cortical processing of co-localized visual stimuli presented after, reflected by better detection rates, better discrimination, and sharper perceived contrast. We replicated the ACOP, using earphones, and tested whether auditory cuing can influence temporal order judgments (TOJ) for two visual stimuli (horizontal arrangement) as well as if the ACOP would predict the amplitude of this influence. A lateral salient sound was followed, after 150 or 630 ms, by the visual presentation of a pair of disks, one in left and one in right hemifield, with variable SOA. The TOJ task was to indicate which disk appeared first or which disk appeared second (controlling for response bias). We observed an ACOP at posterior electrode sites and confirmed our hypothesis that the lateral sound influenced TOJ by accelerating the perception of the disk presented on the cued side, even though the sound was irrelevant to the task. Furthermore, the ACOP amplitude was correlated to this visual perceptual change, indicating that a larger change in brain activity was associated with a faster processing of co-localized visual stimuli.     

Management of blood pressure disorders in individuals with spinal cord injury

Blood pressure regulation is impacted by a spinal cord injury (SCI) due to impaired descending sympathetic vascular control. Common blood pressure problems in the SCI population include persistently low blood pressure with bouts of orthostatic hypotension and autonomic dysreflexia, which are more prevalent in individuals with lesions above the sixth thoracic vertebral level; however, they may occur regardless of the neurological level of injury. Although blood pressure disorders adversely impact daily function and quality of life, most individuals with SCI do not acknowledge this association. Few pharmacological options have been rigorously tested for safety and efficacy to manage blood pressure disorders in the SCI population. Furthermore, clinical management of any one blood pressure disorder may adversely impact others, as such treatment is complicated and not often prioritized.     

Left Atrial Appendage Occlusion,A Misnomer?: Where Do We Go From Here?

The importance of the left atrial appendage (LAA) as the source of thromboembolism including stroke in patients with nonvalvular atrial fibrillation is well documented, with more than 90% of ischemic strokes related to a LAA thrombus. Although oral anticoagulation has been the standard of care, approximately 50% to 60% of patients either have contraindications to oral anticoagulation or do not continue the medication beyond the first year. This led to the development of local site-specific therapy to occlude the LAA by either surgical or transcatheter means. Despite marked advancements, incomplete LAA closure with surgical and transcatheter approaches remains frequent. The etiology of incomplete LAA closure and its clinical implications remain unclear. Multiple strategies are in development including changes in deployment techniques, a new device design, and alternative approaches to leak closure.