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...     

胎儿头面部异常的临床咨询

胎儿头面部异常，是较为常见的结构异常。文章就常见的胎儿头面异常，包括唇腭裂、小颌畸形、耳郭畸形、巨舌症、眼畸形、颈项透明层增厚和颈部淋巴水囊瘤的分型与发生率、影像学诊断、病因、临床处理及预后分别进行论述，为临床决策和咨询提供参考。       

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.     

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [¹²⁵I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.     

Re-engineering the interpretation of electronic fetal monitoring to identify reversible risk for cerebral palsy: a case control series

Background: Even key opinion leaders now concede that electronic fetal monitoring (EFM) cannot reliably identify fetal acidemia which many vouch as the only labor mediated pathophysiologic precursor for cerebral palsy (CP). We have developed the “Fetal Reserve Index” – an algorithm combining five dynamic components of EFM (1. Rate, 2. Variability, 3. Accelerations, 4. Decelerations, and 5. Excessive uterine activity) considered individually that are combined with the presence of: 6. maternal, 7. obstetrical, and 8. fetal risk factors.

Objective: Here, we compare this 8-point fetal reserve index (FRI) against the performance of ACOG monograph criteria and ACOG Category systems for predicting risk for both CP and the need for emergency operative delivery (EOD). We then studied how varied management for screen positives (Red zone-defined below) impacts the outcome of such cases.

Study design: Four hundred twenty term patients were studied: all entered labor with normal EFMs and no apparent cause of harm except events of labor and delivery. Sixty subsequently developed CP, and 360 were apparently normal controls. An FRI, normal on all eight parameters scored 100%, 4 of the 8 was 50%, etc. We divided cases into Green zone >50%, Yellow 50–26%, and Red ≤25%. An FRI in the Red zone was considered a positive screen. We then compared performance metrics for the three evaluation schemes and differences between controls that reached Red against those controls whose worst scores were Green/Yellow.

Results: For detection of injury during labor, the FRI performed much better than the ACOG Category criteria (sensitivity 28%), and Category III (45%) (p?Conclusions: FRI shows better discrimination for adverse fetal outcome and EOD than traditional EFM interpretation. The Category system is a very poor, subjective screening method as the vast majority of CP babies never reach the “action point” result of Category III. While reaching the Red zone does not ordain a bad outcome, how it is managed, does. Compared to CP cases, Red controls were delivered faster, had higher FRIs, and often had prompt management including IR maneuvers, which improved the FRI and lowered the risk of EODs even for cases with normal outcomes. With further study and validation, the quantitative FRI approach may replace the current, very subjective interpretation with a quantitative “lab test” approach.     

Prenatal Diagnosis of Aortopulmonary Window by 2‐Dimensional Echocardiography: Summary of 8 Cases

Aortopulmonary window (APW) is a rare congenital heart anomaly. A total of 8 cases with APW confirmed by echocardiography and surgery were retrospectively reviewed and the echocardiographic features analyzed. Among the 8 APW cases, 5 were type II and 3 were type III, the latter of which includes 2 cases complicated with Berry syndrome. Prenatal echocardiography can provide accurate information for the diagnosis of fetal APW. The prognosis depends on the timing of surgery and the nature of the associated cardiac anomalies.