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...     

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

Hypertensive Crisis during Microwave Ablation of Adrenal Neoplasms: A Retrospective Analysis of Predictive Factors

PurposeTo identify risk factors for hypertensive crisis (HC) during ultrasound-guided percutaneous microwave (MW) ablation of adrenal neoplasms.Materials and MethodsPatients who underwent MW ablation for adrenal tumors between April 2006 and November 2017 were retrospectively identified for this study (51 consecutive patients; 35 males, 16 females; mean age, 55 years; range, 15–85 years). A total of 77 MW ablation treatments were performed for 67 tumors (24 primary [9 pheochromocytomas, 8 adenomas, and 7 cortical carcinomas]; and 43 metastases [22 hepatocellular carcinoma, 8 renal cell carcinoma, 5 non-small cell lung cancer, 4 colorectal cancer, 3 liposarcoma, and 1 malignant fibrous histiocytoma]). The mean diameter of the adrenal tumors was 4.6 cm (range, 1.2–16.2 cm). Information about patient demographics, imaging studies, pathology and laboratory results, procedure records, and clinical outcomes was retrieved and analyzed. Statistical analysis was then performed to determine potential risk factors for HC.ResultsOf the 77 MW ablation procedures, HC occurred in 13 (16.9%). A significantly higher risk of HC was observed in patients with pheochromocytoma (odds ratio [OR], 9.037; 95% confidence interval [CI], 1.731–47.172; P = .009), body mass index <24 kg/m² (OR, 5.167; 95% CI, 1.060–25.194; P = .042), dominant tumor size ≤4.5 cm (OR, 4.023; 95% CI, 1.011–16.005; P = .048), and pre-procedural systolic blood pressure ≥130 mmHg (OR, 0.242; 95% CI, 0.068–0.861; P = .029).ConclusionHC can occur during MW ablation in patients with either primary or metastatic adrenal tumors. Pheochromocytoma, body mass index, tumor size, and pre-procedural systolic blood pressure appear to be significant risk factors for the occurrence of HC.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

大鼠腹侧被盖区多巴胺能神经元介导食欲素促进全麻后觉醒效应

目的:研究大鼠腹侧被盖区(VTA)多巴胺能神经元是否介导食欲素(orexin)的促进全麻后觉醒效应。方法:将兴奋性光遗传病毒注射至Hcrt-cre大鼠的orexin阳性神经元所在的下丘脑外侧穹隆周区(PeFLH),同时在VTA区注射抑制性化学遗传病毒及带有酪氨酸羟化酶(TH)-cre的混合病毒抑制多巴胺能神经元,并在VTA区植入光纤。观察通过化学遗传抑制VTA区多巴胺能神经元后,光遗传兴奋VTA区的orexin阳性神经投射终末是否仍能引起促进异氟醚麻醉后觉醒的效应。结果:与对照组相比,用化学遗传技术预先抑制VTA区多巴胺能神经元,阻断了光遗传兴奋VTA区orexin阳性神经投射终末所产生的缩短大鼠1.4%异氟醚麻醉后觉醒时间的作用;并阻断了光遗传兴奋VTA区orexin阳性神经投射终末所产生的降低大鼠1.4%异氟醚麻醉中脑电图爆发抑制率(BSR)效应。用Fos染色法验证了化学遗传法抑制多巴胺能神经元的可靠性。结论:抑制VTA区的多巴胺能神经元能够阻断兴奋大鼠VTA区orexin阳性神经末梢所产生的促进大鼠异氟醚后觉醒的效应,提示VTA区的多巴胺神经神经元介导了orexin调控VTA区产生的促进觉醒效应。     

Cerebrovascular events during pregnancy and puerperium

Though cerebrovascular complications of pregnancy remain relatively rare, they represent a potentially devastating event that necessitates prompt identification and treatment. Eighteen percent of strokes occurring in young women are linked to pregnancy. They occur mostly in the third trimester or during the post-partum period. Their biggest risk factors are hypertension, preeclampsia/eclampsia and migraine. Cerebrovascular events occurring during this period may involve specific pathophysiological processes that include embolic phenomena or endothelial dysfunction, but can also have common etiologies that are simply favored by the context of pregnancy. Thus, posterior encephalopathy and vasoconstriction cerebral syndrome are relatively frequently involved in cerebrovascular complications of pregnancy. Other very specific causes like amniotic fluid embolism or postpartum cardiomyopathy can also be responsible for such events. The management of stroke during pregnancy must be multidisciplinary and include a neurovascular expertise. Some conditions can lead to a long-life follow-up and modify the management of a future pregnancy.     

Effect of advanced nursing care on psychological disorder in hypertensive retinopathy of pregnancy: A protocol of systematic review

Background:This study will assess the effect of advanced nursing care (ANC) on psychological disorder (PD) in hypertensive retinopathy of pregnancy (HTRP).Methods:This study will search electronic databases from inception to the present (Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, CNKI, and Chinese Biomedical Literature Database), and other sources. All literature sources will be searched without limitations to language and study status. All eligible case-controlled study (CCS) will be included in this study. Two authors will independently carry out literature selection, data collection, and study quality assessment. Any confusion will be solved by a third author through discussion. Statistical analysis will be conducted using RevMan 5.3 software. In addition, a narrative synthesis will be elaborated if it is necessary.Results:This study will summarize most recent high quality evidence to appraise the effect of ANC on PD in HTRP.Conclusion:The results of this study will seek to identify the effect of ANC on PD in HTRP among pregnancy population.OSF registration:osf.io/hgp93.     

全身振动训练联合正弦交变电磁场对去卵巢骨质疏松大鼠骨密度、骨代谢指标的影响研究

目的探讨全身振动训练联合正弦交变电磁场对去卵巢骨质疏松大鼠骨密度、骨代谢、骨生物力学性能的影响。方法将100只大鼠随机分为切除卵巢组和对照组,分别进行卵巢切除术和假手术,大鼠进行6周恢复,恢复后将造模成功的切除卵巢大鼠随机分为模型组(MO组)、全身振动训练组(W组)、正弦交变电磁场组(S组)、全身振动训练+正弦交变电磁场组(WS组),对照组列为假手术组(SO组),进行为期16周干预,干预结束后对大鼠进行骨密度、骨代谢、骨生物力学性质的检测。结果16周干预完成后,MO组、S组大鼠体质量显著高于SO组、W组、WS组大鼠(P0. 05); W组、WS组、SO组大鼠骨密度指标、血清雌二醇浓度指标明显高于大鼠MO组(P0. 05); SO组大鼠血清雌二醇浓度指标明显高于S组、W组、WS组(P0. 05); M组大鼠血清OC、ALP浓度明显高于SO组、W组、S组、WS组大鼠(P0. 05);尿液DPD/Cre、Ca/Cre、P/Cre浓度方面,M组大鼠明显高于SO组、W组、S组、WS组大鼠(P0. 05)。SO组、W组、S组、WS组大鼠股骨最大载荷和弹性模型明显高于MO组大鼠(P0. 05)。SO组、W组、S组、WS组大鼠股骨断裂载荷组间无明显差异(P0. 05); SO组、W组、S组、WS组大鼠股骨弹性模量明显高于MO组大鼠(P0. 05)。SO组大鼠股骨弹性模量明显高于S组大鼠(P0. 05),但与W组、WS组大鼠没有明显差异(P0. 05)。L4椎体压缩试验,SO组、W组、S组、WS组大鼠股骨最大载荷和弹性模型明显高于MO组大鼠(P0. 05)。SO组大鼠高于S组、W组,差异有统计学意义(P0. 05),但与WS组大鼠没有明显差异(P0. 05)。结论全身振动训练、正弦交变电磁场、全身振动训练联合正弦交变电磁场3种干预方式施用于去卵巢骨质疏松大鼠均能提升骨密度、抑制骨吸收、平衡骨代谢、改善骨骼结构力学和材料力学性能。而全身振动训练联合正弦交变电磁场能的治疗效果优于单纯使用全身振动训练或正弦交变电磁场,在临床应用中有一定推广价值。