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。
Background: The incidence of cryptococcal meningitis (CM) and tuberculous meningitis (TBM) have gradually increased in recent years. These two types of meningitis are easily misdiagnosed which leads to a poor prognosis. In this study we compared differences of clinical features and prognostic factors in non-HIV adults with CM and TBM. Methods: We retrospectively reviewed the medical records of CM and TBM patients from January 2008 to December 2015 in our university hospital in China. The data included demographic characteristics, laboratory results, imaging findings, clinical outcomes. Results: A total of 126 CM and 105 TBM patients were included. CM patients were more likely to present with headache, abnormal vision and hearing, and they might be less prone to fever and cough than TBM patients (P < 0.05). Higher percentage of CM patients presented with cerebral ischemia/infarction and demyelination in brain MRI than TBM patients (P < 0.05). CM patients had lower counts of WBC in CSF, lower total protein in CSF and serum CD4/CD8 ratio than TBM patients (P < 0.05). After three months of treatment, CM group have worse outcome than TBM group (P < 0.05). Multivariate analysis showed that age more than 60y (OR = 4.981, 95% CI: 1. 955-12.692, P = 0.001), altered mentation (OR = 5.054, 95% CI: 1.592-16.046, P = 0.006), CD4/CD8 ratios < 1 (OR = 8. 782, 95% CI: 2.436-31.661, P = 0.001) and CSF CrAg >= 1: 1024 (OR = 4.853, 95% CI: 1.377-17.098, P = 0.014) were independent risk factors for poor prognosis for CM patients. For TBM patients, hydrocephalus (OR = 7.290, 95% CI: 1. 630-32.606, P = 0.009) and no less than three underlying diseases (OR = 6.899, 95% CI: 1.766-26.949, P = 0.005) were independent risk factors, headache was a protective factor of prognosis. Conclusions: Our study provided some helpful clues in the differential diagnosis of non-HIV patients with CM or TBM and identified some risk factors for the poor prognosis of these two meningitis which could help to improve the treatment outcome. Further studies are worth to be done.
Here, the authors present a thermo-responsive shape memory polymer (SMP) foam that can be programmed to control the preosteoblast behavior by changing porous architecture during cell cultivation. The preosteoblast cells are seeded on the SMP foams with temporarily compressed pore structure. Results show that cells preferentially align along the pore length direction. After the pore recovery at 37 degrees C, cells remain attached and viable but change their topography in a tangential direction along the pore edge. This work indicates the shape-memory actuated porous structure in SMP foam can control the cell behavior. This may provide an effective method for studying cell responses to dynamic environment and facilitate the healthy and optimal development of tissue engineering.
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] 。
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.
A small amount of research has examined the association between the belief in free will and subjective well-being (SWB) among Western laypersons from individualist cultures. However, no study has examined this association among participants from collectivist cultures (e.g., Eastern Asian cultures). Therefore, in this study, we explored this association among two large, independent cohorts of Chinese adolescents (N-1 = 1,660; N-2 = 639; high school students). The belief in free will was measured by a self-reported questionnaire (Cohorts 1 and 2) and a two-alternative forced choice question regarding the existence of free will (Cohort 2). SWB included cognitive well-being (life satisfaction) and affective well-being (positive and negative affect) in both cohorts. Data analyses indicated that a stronger belief in free will was consistently associated with higher life satisfaction and positive affect in both cohorts. Our investigation provides evidence supporting the cultural generality of the positive effects of believing in free will on SWB.
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.
The purpose of the current study was to compare and investigate the effect of fixed and individual valgus correction angle (VCA) on postoperative alignment restoration. It is hypothesized that individual VCA would be more accurate than fixed VCA in postoperative limb alignment restoration. Four hundred and fifty-two patients with 546 consecutive uncomplicated primary total knee arthroplasties performed by a single surgeon, with 302 knees that had individual VCA (group A) and 244 knees that had fixed 5A degrees VCA (group B), were enroled in this study. Preoperative and postoperative full-length standing hip-to-ankle radiographs were used to assess limb alignment. Postoperative hip-knee-ankle angle (theta), femoral component angle (alpha) and tibial component angle (beta) were measured and compared between the two groups. Mean postoperative theta angle and alpha angle were 178.9A degrees (SD 1.3A degrees) and 89.1A degrees (SD 1.1A degrees) in the group A, whereas they were 177.8A degrees (SD 1.9A degrees) and 87.9A degrees (SD 1.5A degrees) in the group B. There were significant differences in both parameters between the two groups (p = 0.021 and 0.016, respectively). Mean postoperative beta was 89.8A degrees (SD 1.2A degrees) in the group A and 89.7A degrees (SD 1.3A degrees) in the group B, and no significant difference was detected. There were 114 (37.7 %), 221 (73.2 %) and 265 (87.7 %) knees that had restoration of mechanical axis to +/- 1A degrees, +/- 2A degrees, +/- 3A degrees of neutral, respectively, and 37 (12.3 %) outliers (>+/- 3A degrees) in the group A, whereas there were 48 (19.7 %), 122 (50.0 %) and 170 (69.7 %) knees that had restoration of mechanical axis to +/- 1A degrees, +/- 2A degrees, +/- 3A degrees of neutral, respectively, and 74 (30.3 %) outliers in the group B. Group A had a higher percentage of restoration of limb alignment and fewer outliers than those in the group B, and this difference was statistically significant (p < 0.001). The results from the present study demonstrated that individual VCA for distal femoral resection could enhance the accuracy of postoperative limb alignment restoration compared with fixed VCA. For clinical relevance, individual VCA should be recommended for routine use in all patients in order to achieve the expected postoperative neutral limb alignment and reduce the risk of postoperative malalignment due to the planning error of a fixed VCA. Prospective comparative study, Level II.
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。