High altitude increases the expression of hypoxia-inducible factor 1α and inducible nitric oxide synthase with intest-inal mucosal barrier failure in rats

Background: The failure of intestinal mucosal barrier may induce multiple organ dysfunction and systemic inflammatory response syndrome, but little work has been done on whether hypobaric hypoxia related to the failure of intestinal mucosal barrier. Aims: To study the expression of hypoxia-inducible factor 1α (HIF-1α), inducible nitric oxide synthase (iNOS) and morphological changes of intestinal mucosa in albino rats at different altitude. Methods: 30 male Wistar rats raised in plain for one month were randomly divided into 3 groups: Plain 500 m group (n=10), High-altitude (HA) 3842 m group (n=10) and HA4767 m group (n=10). Each group was delivered to different altitude area at the same shipping time and executed after 3 days’ exposure to different altitude. Intestinal segments with the same location of all rats were removed for morphological analyses. Morphologic parameters (villous height, crypt depth, mucosal wall thickness and villous surface area) were measured by optical and scanning electron microscope. The expression of iNOS and HIF-1α were detected by immunohistochemistry. Results: Morphological indexes in higher altitude groups were exacerbated obviously compared with those of lower altitude groups. While the expression of iNOS and HIF-1α in higher altitude groups were significantly increased than those of lower altitude groups. Linear correlation analysis showed that the expression of iNOS was positively correlated with that of HIF-1α. Conclusions: Hypobaric hypoxia increases the expression of HIF-1α and iNOS in intestinal mucosa, however exacerbates the mucous morphologic parameters with altitude increasing. HIF-1α may regulate the expression of iNOS and be involved in the damage of intestinal mucosa.     

Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells

FOXP3⁺ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that high-salt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ — either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown — restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways.     

Immunosuppressive activity of alpinetin on activation and cytokines secretion of murine T lymphocytes

Alpinetin, a flavonoid compound extracted from the seeds of Alpinia katsumadai Hayata, has been known to possess antibacterial, anti-inflammatory and other important therapeutic activities. In the current study, we investigated alpinetin for its immunosuppressive effect on activation and cytokines secretion of murine T lymphocytes. The data showed that alpinetin markedly suppressed ConA-induced murine splenocyte proliferation, Th1/Th2 cytokines production, CD4⁺ T-cell populations and ratio of CD4⁺/CD8⁺. This inspired us to further study the effects of alpinetin in vivo. The results showed that administration of alpinetin suppressed T-cell-mediated delayed-type hypersensitivity reaction in mice. In addition, we studied signal transduction pathways about T-cell activation on puried murine T lymphocytes by Western-blot assay. The data revealed that alpinetin could shock the activation of NF-κB, NFAT2 signal transduction pathways. These observations indicated that alpinetin have potential effects in downregulating the immune system and might be developed as a useful immunosuppressive agent in treating undesired immune responses.     

622例急性肺栓塞患者的临床特点分析

目的:分析急性肺栓塞(Acute pulmonary embolism,APE)患者的临床特征、危险因素、心电图和实验室检查等特点,提高对这种常见的致死性疾病的诊断意识。方法:连续入选2007年1月至2013年12月,在我院经影像学方法诊断的急性肺栓塞患者622例,记录临床特征、危险因素、影像学及实验室检查结果。结果:患者平均年龄(66.4±17.4)岁,女性占54.0%。常见症状是呼吸困难、胸痛和咳嗽,分别占75.4%、37.5%、13.5%和96.1%的PE患者存在三种最常见的症状。常见呼吸急促、心动过速和深静脉血栓形成(DVT)的体征,分别占16.4%、16.1%和15.9%。常见的危险因素是既往深静脉血栓史[肺栓塞(PE)和/或DVT]、恶性肿瘤、外科手术和制动,分别占21.0%、11.3%、13.8%和14.0%。心电图异常的患者占42.9%,包括窦性心动过速、心房颤动、SIQIIITIII、右束支传导阻滞和胸前导联T波明显倒置,分别为15.1%、6.2%、14.3%、4.7%和22.2%。患者入院科室为呼吸科47.9%,心内科40.4%,血管外科5.1%,其他外科3.9%。21.2%的患者接受静脉溶栓,介入溶栓和外科取栓手术患者占10.3%;71.9%单纯抗凝治疗。患者院内死亡21例(3.4%)。结论:PE症状缺乏特异性,很容易与其他疾病误诊,尤其是心内科疾病。危险因素的识别、心电图和超声心动图的表现以及实验室检查结果有助于PE的诊断。     

A study of weekly docetaxel and carboplatin as first-line chemotherapy for advanced non-small cell lung cancer

Background

Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC).

Methods

Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m² on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles).

Results

Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively.

Conclusions

The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.     

Relationship between effort–reward imbalance and hair cortisol concentration in female kindergarten teachers

Objective

The present study aims to investigate the relationship between effort–reward imbalance and hair cortisol concentration among teachers to examine whether hair cortisol can be a biomarker of chronic work stress.

Methods

Hair samples were collected from 39 female teachers from three kindergartens. Cortisol was extracted from the hair samples with methanol, and cortisol concentrations were measured with high performance liquid chromatography–tandem mass spectrometry. Work stress was measured using the effort–reward imbalance scale.

Results

The ratio of effort to reward showed significantly positive association with hair cortisol concentration.

Conclusion

The cortisol concentration in the system increases with the effort–reward imbalance. Measurement of hair cortisol can become a useful biomarker of chronic work stress.