腰痹通胶囊治疗腰椎间盘突出症的Meta分析

目的系统评价腰痹通胶囊比较非甾体抗炎药(NSAIDs)治疗腰椎间盘突出症(LDH)的疗效和安全性,为临床提供循证参考。方法通过计算机检索Cochrane Library、PubMed、Web of Science、中文科技期刊全文数据库(CNKI)、维普数据库(VIP)、万方数据库(Wanfang Data),收集自建库以来至2019年6月腰痹通胶囊比较NSAIDs治疗LDH的随机对照试验(RCT),制定纳入标准和排除标准后,筛选出符合标准的文献,评价纳入文献的质量并提取数据,采用RevMan5.3软件对其进行Meta分析。结果共有10篇研究符合标准,合计1088例患者。Meta分析结果显示腰痹通胶囊治疗LDH与NSAIDs比较在提高临床总有效率[OR=4.74,95%CI(3.13,7.17),P<0.00001]、降低VAS评分[MD=-1.26,95%CI(-1.35,-1.17),P<0.00001]、改善白细胞介素-1β(IL-1β)[MD=-0.12,95%CI(-0.14,-0.10),P<0.00001]、白细胞介素-6(IL-6)[MD=-4.14,95%CI(-6.34,-1.93),P=0.0002]、白细胞介素-8(IL-8)[MD=-9.49,95%CI(-11.73,-7.24),P<0.00001]、肿瘤坏死因子-α(TNF-α)[MD=-0.27,95%CI(-0.36,-0.17),P<0.00001]水平方面均有优势,在安全性方面提示不良反应发生率低,临床使用相对安全。结论腰痹通胶囊与NSAIDs比较能明显提高LDH患者的临床疗效、改善相关指标,且不良反应较少。但由于本研究为二次研究,且纳入文献数量较少、质量较低,尚需大样本、高质量随机对照研究对其临床疗效及安全性进一步证实。     

血清CA125,LDH,β2-MG在非霍奇金淋巴瘤诊断治疗中的意义

 目的 探讨血清CA125,LDH,β2-MG在非霍奇金淋巴瘤（NHL）诊断、治疗中的意义。方法 50例NHL患者,采用放射免疫学方法检测CA125及β2-MG,酶法检测LDH。结果 NHL患者血清CA125,LDH,β2-MG的升高与分期、分组、骨髓浸润、化疗效果、疾病的范围及恶性程度有关。结论 血清CA125,LDH,β2-MG作为NHL患者诊断、临床分期、是否骨髓浸润、疗效判定及预后的辅助指标。     

Effects of Various Pharmaceutical Excipients on the Intestinal Transport and Absorption of Sulfasalazine,a Typical Substrate of Breast Cancer Resistance Protein Transporter

Breast cancer resistance protein (BCRP) transporter is an efflux transporter that utilizes energy from adenosine triphosphate hydrolysis to push its substrates, regardless of the concentration gradient. Its presence on the apical membrane of the intestinal mucosa is a major obstacle for the intestinal absorption of its substrates. In this study, we examined the effects of various pharmaceutical excipients on the intestinal transport and absorption of sulfasalazine, a BCRP substrate. Four excipients, including 0.05% and 0.075% BL-9EX, 0.01% and 0.05% Brij 97, 0.075% Labrasol, and 0.05% and 0.1% Tween 20 decreased the secretory transport of sulfasalazine in an in vitro diffusion chamber. Further investigation in an in situ closed loop experiment in rats showed that 0.05% and 0.1% BL-9EX and 0.1% Brij 97 effectively enhanced the intestinal absorption of sulfasalazine while maintaining minimal toxicity to the intestinal mucosa. However, 0.1% Brij 97 also increased the intestinal absorption of 5(6)-carboxyfluorescein, a paracellular marker compound. These findings suggest that BL-9EX might effectively inhibit the BCRP-mediated efflux of sulfasalazine in vivo, indicating that BL-9EX could improve the intestinal absorption of sulfasalazine and other BCRP substrates.     

Multi-walled carbon nanotube-induced inhalation toxicity: Recognizing nano bis-demethoxy curcumin analog as an ameliorating candidate

Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity.     

Risk factors and clinical profile of thrombotic thrombocytopenic purpura in systemic lupus erythematosus patients. Is this a distinctive clinical entity in the thrombotic microangiopathy spectrum?: A case control study

Introduction

The association of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE) is rare. It is associated with high morbidity and mortality. Information about risk factors and clinical outcomes is scant.

Material and Methods

A retrospective case-control study was performed in a referral center in Mexico City between 1994 and 2013. Patients were diagnosed with TTP if they fulfilled the following criteria: microangiopathic haemolytic anaemia, thrombocytopenia, high LDH levels, normal fibrinogen and negative Coombs’ test. Patients with SLE were diagnosed with ≥ 4 ACR criteria. We included three study groups: group A included patients with SLE-associated TTP (TTP/SLE; cases n = 22, TTP events n = 24); patients with non-autoimmune TTP (NA-TTP; cases n = 19, TTP events n = 22) were included in group B and patients with SLE without TTP (n = 48) in group C.

Results

After multivariate analysis, lymphopenia < 1000/mm3 [OR 19.84, p = 0.037], high SLEDAI score three months prior to hospitalisation [OR 1.54, p = 0.028], Hg < 7 g/dL [OR 6.81, p = 0.026], low levels of indirect bilirubin [OR 0.51, p = 0.007], and less severe thrombocytopenia [OR 0.98, p = 0.009] were associated with TTP in SLE patients. Patients with TTP/SLE received increased cumulative steroid dose vs. NA-TTP (p = 0.006) and a higher number of immunosuppressive drugs (p = 0.015). Patients with TTP/SLE had higher survival than NA-TTP (p = 0.033); however, patients hospitalised for TTP/SLE had a higher risk of death than lupus patients hospitalised for other causes

Conclusions

Lymphopenia is an independent risk factor for TTP/SLE. It is likely that patients with TTP/SLE present with less evident clinical features, so the level of suspicion must be higher to avoid delay in treatment.     

Decreased small dense LDL levels in Gilbert's syndrome

Objective

To investigate the role of small dense low density lipoprotein cholesterol (sd-LDL-C) in the mechanism of decreased incidence of cardiovascular disease in Gilbert's syndrome (GS).

Design and methods

sd-LDL-C, ox-LDL, and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n = 42) and compared to healthy controls (n = 52).

Results

Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls (p < 0.001, p < 0.001 and p = 0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP (r = −0.594, p < 0.001; r = −0.249, p = 0.016 and r = − 0.373, p < 0.001 respectively). In addition, sd-LDL-C was positively correlated with ox-LDL (r = 0.307, p = 0.003).

Conclusions

The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.     

Involvement of caspase-4 in IL-1 beta production and pyroptosis in human macrophages during dengue virus infection

Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1β. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1β production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1β protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1β in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1β synthesis in macrophages during DENV-2 infection.     

IL-1β induces expression of costimulatory molecules and cytokines but not immune feedback regulators in dendritic cells

Dendritic cells play an important role in the initiation of immune reactions. Due to their high capacity to prime T-cell responses, the activation of dendritic cells must be tightly controlled. Because Interleukin-1β (IL-1β) is a key player in autoinflammatory diseases, we compared the ability of IL-1β to activate human dendritic cells and induce immune-regulatory molecules versus the effects induced by pathogen-derived stimuli.Upon activation with either IL-1β or microbial stimuli, monocyte-derived dendritic cells showed enhanced expression of costimulatory molecules, increased secretion of chemokines and cytokines, and the ability to activate T cells. In contrast, immune-feedback molecules, including PD-L1, IL-1RA, IL-10 and SOCS1, were exclusively upregulated in response to microbial stimuli, whereas IL-1β treatment had no inducing effect on them. Thus, the limited capacity of IL-1β to induce potential feedback inhibitors may support its key etiologic role in chronic inflammation and autoinflammatory responses.