现已认识到免疫反应、转录因子核因子κB( NF-κB) 的激活、细胞因子、中性粒细胞的激活和肺泡渗入、凝血级联反应、肾素-血管紧张素系统等多种因素构成的复杂网络参与急性肺损伤/急性呼吸窘迫综合征( ALI/ARDS) 的发病过程[ 1-5] 。虽然脓毒症、创伤、肺炎等ALI/ARDS诱发因素很常见, 但仅有部分病人发生ALI/ARDS, 并且具有相似临床特征的ALI/ARDS病人可有截然不同的结果, 这种异质性引起研究者对影响ALI/ARDS 易感性和预后的遗传因子进行鉴别的浓厚兴趣[ 6] 。由于数量庞大的表现型变异, 不完全的基因外显率、复杂的基因-环境相互作用及高度可能的基因座不均一性而使ALI 遗传学的研究受到挑战[ 7] 。近年来基因组学技术被应用于ALI/ARDS 发病机制的研究, 加深了人们对ALI/ARDS的认识并有可能发展出新的治疗策略以降低其发病率和病死率。
急性肺损伤( ALI) 及急性呼吸窘迫综合征( ARDS) 是各种肺内外致病因素导致的急性呼吸衰竭, 以进行性呼吸困难和顽固性低氧血症为特征, 常继发于休克、创伤、严重感染以及大面积烧伤等疾病。病理以双肺弥漫性的渗出为特点。病情进展迅速, 预后极差, 具有很高死亡率。治疗时需要纠正缺氧, 以保证组织氧供。传统的常规机械通气( CMV) 在改善氧合、呼吸力学参数以及肺内炎症反应的同时, 导致肺损伤, 即呼吸机相关性肺损伤( VALI) 。近年认为, 采用高频振荡通气( HFOV) 代替CMV 能明显避免产生VALI, 并能改善ALI/ARDS的呼吸系统顺应性和氧合作用, 减轻肺内炎症反应和VALI, 利于急性损伤肺内塌陷和闭塞的小气道和肺泡重新开放。并且有人提出HFOV 与部分液体通气( PLV)联用( HFOV-PLV) 可进一步改善气体交换, 抑制肺组织的炎性反应, 减少肺损伤及氟碳化合物( PFCs) 用量, 稳定全身血液循环, 减少中枢神经系统( CNS) 并发症[ 1] 。
ARDS 是引起重症患者呼吸衰竭的主要原因, 尽管医疗技术有了很大的进步, 但对ARDS 的治疗只局限在器官支持层面, 其病死率仍高达40% [ 1] 。ARDS的主要病理改变为肺泡上皮细胞和毛细血管内皮细胞受损, 通透性增加, 富含蛋白质的液体渗出积聚于肺间质和肺泡。因此促进损伤肺毛细血管内皮细胞和肺泡上皮细胞的有效修复可能是ARDS治疗的关键所在。随着干细胞工程学的发展, 间充质干细胞( MSC) 作为一种理想的组织修复来源, 在ARDS 治疗中的应用受到越来越多的关注, 这可能为ARDS 的治疗开辟一条新的途径。
Objective To investigate the effects of high dose ulinastatin with lung protective ventilatory strategies on respiratory function and prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome. Methods Using retrospective analysis, we involved the critical disease patients combined with ALI/ARDS in ICU of The Second Affiliated Hospital of Anhui Medical University. According to whether they were treated with high dose ulinastatin with lung protective ventilatory strategies or not, the patients were divided into the treatment group and the control group. Then pulmonary vascular permeability index (PVPI), extravascular lung water index (EVLWI), oxygenation index, length of SIRS, length of stay in ICU and APACHE Ⅱ score were observed. Statistic analysis was conducted using SPSS 19.0 software. Results A total of 24 patients were included, 13 cases in the treatment group and 11 cases in the control group. After 72 h, PVPI (P=0.016), EVLWI (P=0.045), length of SIRS (P=0.002), length of stay in ICU (P=0.024) and APACHE Ⅱ score (P=0.002) decreased significantly, while oxygenation index (P=0.004) increased significantly in the treatment group compared with the control group. Conclusion High dose ulinastatin with lung protective ventilatory strategies decreased lung capillary permeability, reduced lung blood capillary leakage and extravascular lung water, resulted in the improvement of lung oxygenation function, decreased of length of stay in ICU and the improvement of prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome.
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed.
The quality of reporting practice guidelines is often poor, and there is no widely accepted guidance or standards for such reporting in health care. The international RIGHT (Reporting Items for practice Guidelines in HealThcare) Working Group was established to address this gap. The group followed an existing framework for developing guidelines for health research reporting and the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach. It developed a checklist and an explanation and elaboration statement. The RIGHT checklist includes 22 items that are considered essential for good reporting of practice guidelines: basic information (items 1 to 4), background (items 5 to 9), evidence (items 10 to 12), recommendations (items 13 to 15), review and quality assur-ance (items 16 and 17), funding and declaration and management of interests (items 18 and 19), and other information (items 20 to 22). The RIGHT checklist can assist developers in reporting guidelines, support journal editors and peer reviewers when considering guideline reports, and help health care practitioners understand and implement a guideline.
At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.
Objectives: To compare the proportion of stage I lung cancer and population mortality in China to those in U.S. and Europe where lung cancer screening by low-dose computed tomography (LDCT) has been already well practiced. Methods: The proportions of stage I lung cancer in LDCT screening population in U.S. and Europe were retrieved from NLST and NELSON trials. The general proportion of stage I lung cancer in China was retrieved from a rapid meta-analysis, based on a literature search in the China National Knowledge Infrastructure database. The lung cancer mortality and prevalence of China, U.S. and Europe was retrieved from Globocan 2012 fact sheet. Mortality-to-prevalence ratio (MPR) was applied to compare the population survival outcome of lung cancer. Results: The estimated proportion of stage I lung cancer in China is merely 20.8% among hospital-based cross-sectional population, with relative ratios (RRs) being 2.40 (95% CI 2.18-2.65) and 2.98 (95% CI 2.62-3.38) compared by LDCT-screening population in U.S. and Europe trials, respectively. MPR of lung cancer is as high as 58.9% in China, with RRs being 0.46 (95% CI 0.31-0.67) and 0.58 (95% CI 0.39-0.85) compared by U.S. and Europe, respectively. Conclusions: By the epidemiological inference, the LDCT mass screening might be associated with increasing stage I lung cancer and therefore improving population survival outcome. How to translate the experiences of lung cancer screening by LDCT from developed counties to China in a cost-effective manner needs to be further investigated.
Objective: An amelogenin-derived peptide has been shown to promote remineralization of demineralized enamel in an in vitro model of initial caries induced by pH cycling. The present study examines whether the peptide exerts similar effects within the complex oral environment in vivo. Design: Specific pathogen-free Sprague-Dawley rats (n =36) were infected with Streptococcus mutans, given ad libitum access to Diet 2000 and drinking water supplemented with sucrose (10%, w/v), and then randomly divided into three groups treated with 25 mu M peptide solution, 1 g/L NaF or deionized water. Molar teeth were swabbed twice daily with the respective solutions for 24 days. Then animals were killed, their jaws were removed and caries lesions were analyzed using the quantitative light-induced fluorescence-digital (QLF-D) technique to measure changes in mineral content. To verify QLF-D results, caries were scored for lesion depth and size using the Keyes method, and analyzed using polarized light microscopy (PLM). Results: Mineral gain was significantly higher in teeth treated with peptide or NaF than in teeth treated with water (p < 0.05), based on the QLF-D results (Delta F and Delta Q). Incidence of smooth-surface and sulcal caries based on Keyes scores was similar in rats treated with peptide or NaF, and significantly lower in these groups than in rats treated with water (p < 0.05). Lesions on teeth treated with peptide or NaF were shallower, based on PLM. No significant differences were observed between molar enamel caries treated with peptide or NaF. Conclusions: This amelogenin-derived peptide can promote remineralization in a rat caries model, indicating strong potential for clinical use. (C) 2016 Elsevier Ltd. All rights reserved.