現已認識到免疫反應、轉錄因子核因子κB( NF-κB) 的激活、細胞因子、中性粒細胞的激活和肺泡滲入、凝血級聯反應、腎素-血管緊張素系統等多種因素構成的復雜網絡參與急性肺損傷/急性呼吸窘迫綜合征( ALI/ARDS) 的發病過程[ 1-5] 。雖然膿毒癥、創傷、肺炎等ALI/ARDS誘發因素很常見, 但僅有部分病人發生ALI/ARDS, 并且具有相似臨床特征的ALI/ARDS病人可有截然不同的結果, 這種異質性引起研究者對影響ALI/ARDS 易感性和預后的遺傳因子進行鑒別的濃厚興趣[ 6] 。由于數量龐大的表現型變異, 不完全的基因外顯率、復雜的基因-環境相互作用及高度可能的基因座不均一性而使ALI 遺傳學的研究受到挑戰[ 7] 。近年來基因組學技術被應用于ALI/ARDS 發病機制的研究, 加深了人們對ALI/ARDS的認識并有可能發展出新的治療策略以降低其發病率和病死率。
Background: The association between CD14-159C/T polymorphism and sepsis has been assessed but results of current studies appeared conflicting and inconstant. This analysis was aimed to determine whether the CD14-159C/T polymorphism confers susceptibility to sepsis or is associated with increased risk of death from sepsis. Method: The authors conducted a comprehensive search of PubMed, EMBASE, ISI Web of Science, Cochrane library, ScienceDirect, Wiley Online Library and CNKI databases according to a prespecified protocol. Language limits were restricted to English and Chinese. Two reviewers independently selected the articles and extracted relevant data onto standardized forms. Disagreements were settled by discussion and suggestions from senior consultants. The strength of association were evaluated by odds ratio (OR) and 95% confidence interval (CI). Studies failed to fit the Hardy-Weinberg-Equilibrium were excluded. Results: The research identified a total of 2317 full-text articles of which 14 articles met the predefined inclusion criteria. Meta-analysis was performed for allele frequency of C versus T, as well as genotypes CC + CT versus TT (dominant model), CC versus TT + CT (recessive model), CT versus TT and CC versus TT (additive model). All control samples were in Hardy-Weinberg proportion. No significant association between CD14-159C/T polymorphism and sepsis susceptibility or mortality were detected in the overall population. Nonetheless, subgroup analysis of Asian ethnicity revealed significant association between the CD14-159C/T polymorphism and susceptibility to sepsis in additive model (CC versus TT: OR = 0.52, 95% CI 0.29-0.92, p = 0.03) and recessive model (CC versus CT + TT: OR = 0.50, 95% CI 0.30-0.84, p = 0.009). Of note, three out of the five papers included in the subgroup focused exclusively on burn ICU patients. Conclusions: This meta-analysis demonstrated that CD14-159C/T polymorphism is likely to be associated with susceptibility to sepsis in Asian population, especially for the TT genotype. However, bias may rise for etiologic reasons because the majority of subjects in the subgroup came from burn ICU. CD14-159C/T polymorphism is not relevant to sepsis mortality in any genetic models, regardless of the ethnicities. Due to the exploratory nature of the study, no adjustment for multiple testing was adopted, and therefore the results should be interpreted with precaution. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.
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.
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.
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.
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.
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.
Background: Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. Methods: A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. Results: AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. Conclusions: Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together.
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.
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.