Abstract： Objective To investigate the effects of hepatocyte growth factor（HGF）gene transfected bone marrow mesenchymal stem cells （MSCs）transplantation in pigs with chronic ischemic heart disease. Methods MSCs were isolated from pig bone marrow by density gradient centrifugation and adherent cell culture, purified, and determined by cellsurface antigens（CD34, CD44, CD71, Ⅷ factor and desmin）. MSCs were transfected by adenovirus expressing hepatocyte growth factor（AdHGF）, and the influence of HGF on the biological characteristics of MSCs was tested. The pig model of chronic myocardial ischemia was established by placing Ameroid ring inside the left circumflex coronary artery via leftthoracotomy. A total of 40 pigs were randomly divided into 5 groups （n=8） and were injected 5×106/ml MSCs＋ 4×109 pfu 200 μl AdHGF （MSCs＋ AdHGF group）, 4×109 pfu 200 μl AdHGF （AdHGF group）, 5×106/ml MSCs 200 μl（MSCs group），4×109 pfu 200 μl AdNull （AdNull group）and 1 ml saline（control group） into the ischemic myocardiumrespectively. Echocardiogram, digital subtraction angiography （DSA） of coronary artery, single photon emission computed tomography（SPECT） myocardial perfusion imaging and cardiomyocyte apoptosis were examined after 4 weeks. Results Positive CD44 and CD71 and negative CD34, Ⅷ factorand desmin were detected in MSCs by flow cytometer. HGF had a b influence on stimulating the proliferation and differentiation of MSCs. Echocardiogram examination showed that left ventricular end-diastolic volume（LVEDV），left ventricular ejection fraction（LVEF），fractional shortening（FS）of MSCs＋ AdHGF group were significantly increased after treatment （P＜ 0.05）. DSA detection showed that ischemic neovascularization of MSCs＋ AdHGF group was significantly higher than those of AdHGF group and MSCs group （P＜ 0.05）. SPECT showed that the left ventricular myocardium of MSCs＋ AdHGF group appeared thickened,myocardial perfusion was significantly improved and the myocardial motion was significantly increased （P＜ 0.05）. Vascular density of MSCs＋ AdHGF group was significantly higher than those of AdHGF group and MSCs group by HE stain of myocardium ［（39.4±1.2）/ HPF vs. （36.5±1.4）/ HPF and（34.5±1.7）/ HPF，P＜ 0.05］. Cardiomyocyte apoptosis rate of MSCs＋ AdHGF group was significantly lower than those of AdHGF group and MSCs group by TUNEL stain （P＜ 0.05）. Conclusion Combination transplantation can promote the angiogenesis of chronic ischemic myocardium, inhibit cardiomyocyte apoptosis and improve heart function in pigs with chronic ischemic heart disease. The effect of HGF gene transfected MSCs transplantation is better than that of MSCs or HGF transplantation alone.
Objective To observe the influences of depolarized arrest and hyperpolarized arrest on alternation of fluidity of myocardial cell membrane during cardiopulmonary bypass (CPB) and evaluate the protective effects on myocardium of hyperpolarized arrest. Methods Seventy-two felines were randomized into three groups, each group 24. Control group: 180 minutes of CPB was conducted without aortic and vena caval cross-clamping. Depolarized arrest group: hearts underwent 60 minutes of global ischemia after aortic cross-clamping (ACC) followed by 90 minutes of reperfusion. The cardioplegic solution consisted of St. Thomas solution (K+16mmol/L). Hyperpolarized arrest group: the protocol was the same as that in depolarized arrest group except that the cardioplegic solution consisted of St.Thomas solution with pinacidil (50 mmol/L,K+5mmol/L). Microviscosity, the reciprocal of fluidity of myocardial membrane was measured in all groups by using fluorescence polarization technique. (Results )Microvis cosity of myocardial cell in depolarized arrest group during ACC period was significantly higher than that before ACC and kept on rising during reperfusion period. Microviscosity of myocardial cell in hyperpolarized arrest group during ACC was trending up and reperfusion periods as well, but markedly lower compared to that in depolarized arrest group at corresponding time points(Plt;0.01). Conclusion Hyperpolarized arrest is more effective in protecting myocardial cells from ischemia-reperfusion injury than depolarized arrest during CPB by maintaining better fluidity of myocardial membrane.
ObjectiveTo systematically review the effectiveness and safety of thalidomide for ankylosing spondylitis (AS). MethodsDatabases including Ovid MEDLINE (1946 to 2014.2.1), EMbase (1947 to 2014.2.1), CENTRAL (Issue 1, 2014), CBM (1978 to 2014.2.1), CNKI (1994 to 2014.2.1), WanFang Data (1980 to 2014.2.1) and VIP (1989 to 2014.2.1) were searched for randomized controlled trials about the effectiveness and safety of thalidomide for AS. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Meta-analysis was then conducted using RevMan 5.2 software. ResultsSeven RCTs were included involving 544 patients. The results of meta-analysis showed that, compared with the blank group, thalidomide increased clinical remission, but it showed no obvious advantage in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and secondary outcome index, with an increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; and for other outcomes it was similar to SSZ. Compared with NSAIDs, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; it increased clinical remission; for secondary outcomes it was similar to NSAIDs; and it had a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop-out. ConclusionCompared with the blank group, thalidomide increases clinical remission, with an obviously-increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20. Compared with NSAIDs, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20; it also increases clinical remission; but it has a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop-out. Due to limited quantity and quality of the included studies, the above conclusion needs to be verified by conducting more high quality studies.
目的 总结肺隔离症的临床特点、诊断方法及治疗的经验，降低误诊率，提高治疗水平。 方法 回顾性分析福州总医院2002年7月－2012年6月收治的27例肺隔离症患者的临床诊治手段。 结果 27例肺隔离症患者中，术前确诊仅有18例，误诊为肺部良性肿瘤3例，肺脓肿3例，支气管扩张2例，纵隔肿瘤1例。行外科切除的患者有19例，其中13例经胸腔镜手术，6例开胸手术，均无复发；行支气管动脉数字减影血管造影栓塞术8例，其中再发咯血1例来院行手术治疗。 结论 外科治疗是目前肺隔离症治疗的主要方法。围手术期积极控制感染对治疗的成功有显著意义。
With the growth of offshore activities, the incidence rates of seawater drowning (SWD) induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) increase significantly higher than before. Pulmonary interstitial edema, alveolar septum fracture, red blood cells, and inflammatory cells infiltration can be seen under light microscope in the pathologic changes of lungs. The major clinical manifestations are continual hyoxemia and acidosis, which lead to a severe condition, a high death rate, and a poor treatment effect. Bone marrow mesenchymal stem cells are capable of self-renewal, multilineage differentiation and injured lung-homing, which are induced to differentiate into alveolar epithelial cells and pulmonary vascular endothelial cells for tissues repairing. This may be a new way to treat SWD-ALI and SW-ARDS.
Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which was obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), GO analysis, KEGG analysis, and GSEA, to analyze the data were employed. Our objective was to establish a five-gene panel risk assessment model using Cox regression and LASSO regression. Based on this model, we constructed a Nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, ROC curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as Metabolism of xenobiotics by cytochrome P450, Natural killer cell-mediated cytotoxicity, Antigen processing and presentation, and Regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the ROC curve (AUC) of 0.675, as well as in time-dependent ROC curves. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a Nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.
ObjectiveTo explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). MethodsThe Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. GO, KEGG, and GSEA enrichment analyses were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients' 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Finally, single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. ResultsDifferentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. Through scRNA-seq analysis, RORA and KLF10 were mainly expressed in natural killer cells. ConclusionThe prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.