KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.

An Empirical Study on the Coupling and Coordination of Health Investment, Resident Health and Economic Growth in Sichuan Province —Based on a Modified Coupling Model

We should calculate the coupling degree of medical investment, resident health and economic growth in Sichuan Province, and make clear the coordinated development of the aforementioned three factors. In that, the government was able to formulate policies that feature the positive interaction and coordinated development of regional medical investment, health and economy. Methods on index system for the evaluation of health investment, resident health and economic growth were constructed, and the coupling and coordination degree of the three systems were empirically studied based on the entropy weight method, the coupling coordination model and the gray correlation method. From the perspective of time series, the overall coupling and coordination level of Sichuan Province is relatively low, and the comprehensive development level of health investment and economic growth system has lagged behind the resident health system;from the perspective of spatial distribution characteristics, in 2019, the coordinated development level of health investment resident health and economic growth coupling in western Sichuan, southern Sichuan, northern Sichuan, eastern Sichuan and northern Sichuan is in the primary coordination stage, but there is a lag in the development of the health investment system between western Sichuan and southern Sichuan, and there is a lag in the development of the economic growth system between northern Sichuan and eastern Sichuan. From the analysis of gray correlation degree, the main correlation factors are diverse. All in all, the overall coordination level of health investment, resident health and economic growth in Sichuan Province is relatively low, and in order to achieve its coordinated development, it is necessary to narrow regional differences, formulate coordinated development strategies according to local conditions, and improve the overall coordination level.

MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways

AIM:To determine how the oncogene mi R-21 regulates the RAS signaling pathways and affects colon cancer cell behaviors.METHODS:RAS p21 GTPase activating protein 1(RASA1) protein expression in six colon cancer cell lines was assessed by Western blot.Colon cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly decreased.RKO cells were transfected with vectors overexpressing or downregulating either mi R-21 or RASA1.Furthermore,a luciferase reporter assay was used to determine whether RASA1 is a gene target of mi R-21.Then,changes in m RNA and protein levels of RASA1,RASGTP,and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction,Western blot and immunoprecipitation.Finally,cell proliferation,apoptosis,invasion,and tumorformation ability w ere assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay,flow cytometry,transwell assay,and animal experiment,respectively.RESULTS:RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines,and RASA1 was confirmed as a target gene of mi R-21.Interestingly,RASA1 m RNA and protein levels in pre-mi R-21-LV(up-regulation of mi R-21) cells were lower than those in anti-mi R-21-LV(down-regulation of mi R-21) cells(P < 0.05).In addition,pre-mi R-21-LV or si RASA1(down-regulation of RASA1) cells showed higher cell proliferation,reduced apoptosis,increased expression of RAS-GTP,p-AKT,Raf-1,KRAS,and p-ERK1/2,and higher invasion and tumor formation ability,compared with control,antimi R-21-LV or pc DNA3.1-RASA1(up-regulation of RASA1) cells(P < 0.05).CONCLUSION:RASA1 is a target gene of mi R-21,which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.

Predictive value of serum uric acid on left atrial spontaneous echo contrast in non-valvular atrial fibrillation patients

ObjectivesTo 调查在浆液之间的关系尿酸( SUA )和左 atrial 在纤维性颤动( AF ) patients.MethodsWe 回顾地屏蔽了的非瓣膜的 atrial 的自发的回响对比(LA秒)在 radiofrequency 以前经历了 transesophageal echocardiography 的有 AF 的 1,476 个连续就医的病人导管脱离，在广东医院将军的左 atrial 附器闭合和电的 cardioversion 。所有病人的临床的基线特征上的数据与左 atrial 血栓从电子医药记录和病人的 analyzed.ResultsAfter 排除被收集， 1,354 个病人进入了现在的学习， 57 是 LA 秒。吝啬的女 SUA 水平(380.88 &#x000b1；94.35 &#x000b5； mol/L 对 323.37 &#x000b1；72.19 &#x000b5； mol/L， P &#x0003c；0.001 ) 并且男 SUA 水平(416.97 &#x000b1；98.87 &#x000b5； mol/L 对 367.88 &#x000b1；68.50 &#x000b5； mol/L， P = 0.008 ) 比在控制在有 LA 秒的病人更高显著地是两个。吝啬的左 atrial 尺寸(41.32 &#x000b1；5.12 公里对 36.12 &#x000b1；5.66 公里， P &#x0003c；0.001 ) 在有 LA 秒的病人是显著地更大的。在 multivariate 回归分析， SUA 水平是为 LA 秒的一个独立风险因素(或：1.008， P &#x0003c；0.001 ) 。在操作典型曲线分析的接收装置，在为在女性和男性预言 LA 秒的 SUA 的曲线下面的相应区域分别地是 0.670 和 0.657。SUA 水平在有 LA-SEC.ConclusionSUA 的非瓣膜的 AF 病人是显著地更高的水平是一个独立风险因素并且在南部的中国在非瓣膜的 AF 病人之中为 LA 秒有中等预兆的价值。

Identification of a 10-pseudogenes signature as a novel prognosis biomarker for ovarian cancer

The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biomarkers and therapeutic targets for ovarian cancer.

Hyperbaric oxygen protects against PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion via the inhibition of cell apoptosis and autophagy

In this study,we investigated the protective effect of hyperbaric oxygen(HBO)on PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion and its possible mechanism.PC12 and H9C2 cell oxygen-glucose deprivation/reperfusion model were established.Cells were divided into a control group,model group,hyperbaric air(HBA)group and HBO group.The cell viability was detected by the CCK8 assay.Hoechst 33342 and PI staining assays and mitochondrial membrane potential(MMP)assays were used to detect cell apoptosis.The ultrastructure of cells,including autophagosomes,lysosomes,and apoptosis,were examined using a transmission electron microscope.The expression of autophagy-related proteins was detected by cellular immunofluorescence and immunocytochemistry.Our results showed that HBO can significantly improve the vitality of damaged PC12 and H9C2 cells caused by oxygen–glucose deprivation/reperfusion.HBO can significantly inhibit apoptosis of PC12 and H9C2 cells caused by oxygenglucose deprivation/reperfusion.Importantly,we found that the protective mechanism of PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion may be related to the inhibition of the autophagy pathway.In this study,the results of cellular immunofluorescence and immunocytochemistry experiments showed that the 4E-BP1,p-AKt and mTOR levels of PC12 and H9C2 cells in the model group decreased,while the levels of LC3B,Atg5 and p53 increased.However,after HBO treatment,these autophagy-related indexes were reversed.In addition,observation of the cell ultrastructure with transmission electron microscopy found that in the model group,a significant increase in the number of autophagic vesicles was observed.In the HBO group,a decrease in autophagic vesicles was observed.The study demonstrated that hyperbaric oxygen protects against PC12 and H9C2 cell damage caused by oxygen-glucose deprivation/reperfusion via the inhibition of cell apoptosis and autophagy.

Inhibitory Mechanism of Carvedilol on L-type Ca^(2+) Current in Rat Ventricular Myocytes

Objectives The effects of car-vedilol on calcium current (ICa) were investigated inisolated adult rat ventricular myocytes. Methods ICawas recorded by using whole-cell patch-clamp recordingtechnique. Results Carvedilol reversibly inhibited ICain a concentration-dependent manner, carvedilol at 0.1,0.3, 1 and 10 μmol/L in the extracellular solution dec-reased peak ICa by 1.52%, 18.04%, 37.34%and72.18%,respectively. The steady-state inactivation curve of ICawas shifted to more negative potentials, while the activ-ation curve was not altered. The recovery from inactiva-tion was shifted to right direction, it could not berecovered completely. In addition, Pretreatment ofventricular myocytes with prazosin and propranololcouldn’t block the carvedilol-induced reduction of ICa.Conclusions Carvedilol inhibits I C a i n adult ratventricular myocytes by mechanisms involvingpreferential interaction with the inactivated state ofcalcium channel.

Special issue “Photoacoustic imaging: microscopy, tomography, and their recent applications in biomedicine” in visual computation for industry, biomedicine, and art

Photoacoustic(PA)imaging is a promising non-invasive and non-ionizing biomedical imaging modality that emerged in recent years.The articles presented in this special issue describe some of newest progress in this field.We are extremely grateful to all contributing authors.The first part of the issue covers new laser source devel-opment,including fiber lasers and laser diodes.The sec-ond part is dedicated to improving the image resolution through chronic cranial window techniques,virtual-point concept,fast polygon scanning,and Fabry Perot sensing.The third part shows the basic principles of photoacous-tic/ultrasound imaging and its applications.

复方盐酸二甲双胍片的相对生物利用度与药动学研究

AIM: To investigate the relative bioavailability of the test complex Metformin hydrochloride formulations (1.25 mg glibenclaminde and 250 mg metformin hydrochloride per pellet) and evaluate its bioequivalence of the complex compared with individual drug adminstration. METHODS: A randomized, self-control, two-way crossover studies were conducted in 20 healthy volunteers[(24±4) years, (62±7) kg, weight index (21.0±1.9)]. One pellet of fest drug or two pellets of reference (commercially available, 1.25 mg glibenclaminde per pellet and 250 mg Metformin hydrochloride per pellet respectively) were orally administrated and the alternative ones were administrated after a washout time of one week. Serum samples were collected before and after administration within 24 hours. Metformin and glibenclaminde concentrations in serum were measured by HPLC. Pharmacokinetic parameters were analyzed by 3P97 computer program. Cmax, tmax were calculated by raw data, AUC(0-last) was also calculated by the trapezoidal summation method. T-test was applied for the all pharmacokinetic parameters of the test and reference drug, the bioequivalence of Cmax, tmax and AUC(0-last) was analyzed by DAS 1.0 computer program package. RESULTS: The tmax, Cmax, t1/2Ka, t1/2Ke of glibenclaminde were as follows(test vs reference): (2.9±0.6) vs (2.8±0.6) h, (112±26) vs (117±28) μg/L, (1.6±0.4) vs (1.5±0.5) h, (1.6±0.4) vs (1.5±0.5) h, and AUC(0-last), AUC0-∝ were (607±109) vs (608±124) μg·L-1·h, (663±124) vs (655±127) mg·L-1·h, respectively. All parameters of mertiform were: tmax (2.0±0.8) vs (2.0±1.2) h, Cmax (1.7±0.4) vs (1.7±0.5) μg/L, t1/2Ka (0.5±0.5) vs (0.6±0.5) h, t1/2Ke (3.2±1.5) vs (2.8±0.9) h, respectively, and AUC(0-last) (8.4±2.4) vs (8.8±2.6), AUC0-∝ (8.9±2.4) vs (9.3±2.7) mg·L-1·h, respectively. There was no significant difference of all parameters between the test drug and the reference (P>0.05) which indicated the pharmacokinetic property of these two were similar. The relative bioavailability of glibenclaminde and mertiform in test drug were 101%±14% and 106%±22%. The analysis of variance tests on Cmax, tmax and AUC(0-last) of glyburide and Metformin right after conversion were qualified. The mean square analysis and two-side t-test of log-transformed data of the Cmax, tmax and AUC(0-last) of glibenclaminde and mertiformare were also qualified. CONCLUSION: The glibenclaminde and mertiform in the test complex pellet are bioequivalent of that of the reference.

复方硝苯地平阿替洛尔缓释片药代动力学和生物等效性研究

AIM: Nifedipine and atenolol are the representative drugs for calcium antagonists and β-blockers, their combination use is the highly acclaimed anti-hypertension programs in clinical application. In order to assess the interaction of the two drugs, the bioequivalence and pharmacokinetics were investigated in a double layer tablet of compound formulation containing a sustained-release(SR) Nifedipine plus an immediate-release(IR) atenolol, compared with atenolol-IR tablet and Nifedipine-IR tablet individually in healthy Chinese subjects. METHODS: There were two stage tests: single-dose and multi-dose. In single-dose test, two random cross-over studies were performed in 20 young subjects who were given as monotherapy, a compound tablet (tested-drug, containing Nifedipine-SR 10 mg and atenolol-IR 25 mg) or two individual tablets (control-drug, a single Nifedipine-IR 10mg and a single atenolol-IR 25 mg) followed by a 12-hour-fast. In multi-dose test, two cross-over studies were performed in another 18 young subjects who were continuously treated for 7-days by two compound tablets once daily or two individual tablets (a single Nifedipine-IR 10 mg and a single atenolol-IR 25 mg) twice daily. The blood samples were collected at different time points before and after drug administration. Plasma drug concentrations were assessed by determining atenolol and Nifedipine with a validated HPLC or GC method. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters. RESULTS: No serious adverse events occurred in all subjects. There were no significant differences in pharmacokinetic parameters between atenolol in compound tablet and atenolol in single tablet. Cssmax, Cav and DF of Nifedipine sustained-release formulation were significantly decreased (90% CI, P<0.05), and tmax was significant extended (90% CI, P<0.05), compared with those of Nifedipine immediate-release tablet formulation in multi-dose studies. In single-dose treatment, the bioavailability of atenolol and nifidipine was 100%±14% and 124%±22%, individually. In multi-dose treatment, the bioavailability of atenolol and nifidipine was 85%±10% and 87%±16%, individually. CONCLUSION: Bioequivalence is equal in comparison between the fixed compound tablet and the individual tablets. The fixed compound tablet consistently provides fairly constant and effective atenolol concentrations. Nifedipine in the test drug is of sustained-release characters.

ZBTB7A governs 2-DG-inhibited glycolysis by regulating GLUT1 in nasopharyngeal carcinoma

Our previous studies suggested a potential interaction between the POK erythroid myeloid ontogenic factor ZBTB7A and glucose transporter 1(GLUT1)in nasopharyngeal carcinoma(NPC).This study was designed to confirm the interaction and further evaluate the precise mechanism by which ZBTB7A and GLUT1 regulate NPC development.The binding sites between ZBTB7A and the promoter of GLUT1 were predicted by bioinformatics.Gene expression was measured by quantitative real-time polymerase chain reaction(qPCR),western blotting,and immunohistochemistry.The activities of key glycolysis enzymes,including hexokinase(HK),pyruvate kinase(PK),lactate dehydrogenase(LDH),and lactate,were detected using specific enzyme-linked immunosorbent assay kits.The connection between ZBTB7A and GLUT1 was analyzed by dual-luciferase reporter assay and chromatin immunoprecipitation-qPCR.The vitality,proliferation,and tumorigenicity of the cells expressing different levels of ZBTB7A were tested by adding the glycolysis inhibitor 2-deoxy-D-glucose(2-DG),followed by MTT,colorimetric focus forming,and xenograft assays,respectively.Our results showed that high expression of GLUT1 was associated with late-stage NPC.After constructing stably transfected cells with lentiviruses,ZBTB7A was effectively knocked down in 5-8F cells(RNAi-5-8F)and overexpressed in 6-10B cells(ZBTB7A-6-10B).The up-or downregulation of GLUT1 secondary to ZBTB7A changes was also limited.The vitality and proliferation of the cells expressing low ZBTB7A were notably blocked by 2-DG.The cells expressing high ZBTB7A were not very sensitive to 2-DG.The growth of RNAi-5-8F xenografts was strongly suppressed by 2-DG.The activities of HK,PK,and LDH were suppressed by 2-DG in the cells expressing low ZBTB7A.RNAi-5-8F cells had the lowest 2-DG-induced lactate production.ZBTB7A directly suppressed the promoter region of GLUT1 to regulate GLUT1 expression.Thus,ZBTB7A controls the 2-DG-induced inhibition of glycolysis by affecting GLUT1.

层粘连蛋白5高表达可能是肺癌患者吉非替尼疗效差的预测因子(英文)

Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog- enous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR,Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut- point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.

Optimization of cerebral organoids:a more qualified model for Alzheimer’s disease research

Alzheimer’s disease(AD)is a neurodegenerative disease that currently cannot be cured by any drug or intervention,due to its complicated pathogenesis.Current animal and cellular models of AD are unable to meet research needs for AD.However,recent three-dimensional(3D)cerebral organoid models derived from human stem cells have provided a new tool to study molecular mechanisms and pharmaceutical developments of AD.In this review,we discuss the advantages and key limitations of the AD cerebral organoid system in comparison to the commonly used AD models,and propose possible solutions,in order to improve their application in AD research.Ethical concerns associated with human cerebral organoids are also discussed.We also summarize future directions of studies that will improve the cerebral organoid system to better model the pathological events observed in AD brains.

Collagen fiber anisotropy characterization by polarized photoacoustic imaging for just-in-time quantitative evaluation of burn severity

Just-in-time burn severity assessment plays a vital role in burn treatment and care.However,it is still difficult to quantitatively and promptly evaluate burn severity by existing medical imaging methods via initial burn depth measurement since burn wounds are usually dynamically developed.As an elastic skeleton of skin,the degree of conformational changes of collagen fibers caused by overheating can reflect the burn severity in a timelier manner.Herein,the polarized photoacoustic technique(PPAT)for just-in-time quantitative evaluation of burn severity via collagen fiber anisotropy assessment is proposed.First,phantom experiments demonstrate the ability of PPAT for deep imaging in a transport mean free path and accurately quantify changes in microstructural order by thermal damage.Then,the Pearson correlation coefficient of the PPAT in assessing burn severity is shown to be up to 0.95,validated by burn skin samples.The PPAT provides a just-in-time quantitative strategy for burn severity evaluation.

Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.

Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands

有严重完整厚度的灼伤损害的背景病人受不了他们的无能因为完全的 destructed 汗腺不能被改革，通过排汗维持身体温度。因为他们的容易的纯化和 multipotency，骨头导出髓的间充质的干细胞(BM-MSCs ) 为房间治疗代表理想的干细胞来源。在这研究，我们试图导致人的 BM-MSCs 通过 ectodysplasin (EDA ) 为汗腺新生区分进汗腺房间基因 transfection。EDA 和 EDA 受体(EDAR ) 的动态表示第一在胚胎学的开发期间在汗腺形成被观察的方法。在有 EDA 表示向量的 transfection 以后，人的 BM-MSCs 被移植进灼伤动物模型的受伤区域。汗腺的新生被排汗测试和 immunohistochemical 分析识别。结果 EDA 和 EDAR 的内长的表示在人的胎儿的皮肤与汗腺开发相关。在 EDA transfection 以后， BM-MSC 获得了 sweat-gland-cell 显型，由流动 cytometry 分析由他们汗腺标记的表示证实了。染色的 Immunohistochemical 揭示了一显著地到在烫伤的爪的汗腺的新生的 EDA-transfected BM-MSCs 的贡献。为为与 EDA-transfected BM-MSCs 对待的爪的排汗测试的积极的率比与 BM-MSCs 或 EDA 表示向量(P 0.05 ) 对待的那些显著地高。我们的结果在汗腺的发展证实了 EDA 的重要角色的结论。有 EDA 的 BM-MSCs transfected 显著地改进了汗腺新生。这研究为受伤皮肤和它的附器的修理和新生建议修改 EDA 的 MSC 的潜在的申请。

Use of a disposable circumcision suture device versus conventional circumcision： a systematic review and meta-analysis

这系统的评论在冗余的包皮和 phimosis 的治疗估计了可处理的割礼缝术设备(DCSD ) 和常规割礼(CC ) 的安全和功效。二个独立评论家在中国和国外为冗余的包皮或 phimosis 的处理用 DCSD 和 CC 为使随机化的控制试用(RCT ) 进行了文学搜索。九 RCT (1898 个盒子) 被包括。与 CC 组相比， DCSD 组有一更短的起作用的时间(标准化吝啬的差别[SMD ]= 21.44；95% 信心间隔[95% CI ][25.08， 17.79 ] ；P < 0.00001 ) ，更短的创伤愈合时间(SMD = 3.66；95% CI [5.46， 1.85 ] ；P < 0.0001 ) ，更少的 intraoperative 血损失(SMD = 9.64；95% CI [11.37， 7.90 ] ；P < 0.00001 ) ，更好化妆的阴茎外观(机会比率[或]=8.77；95% CI [5.90， 13.02 ] ；P < 0.00001 ) ，更低的 intraoperative 疼痛分数，更低的 24-h 手术后的疼痛分数，感染的更低的发生，更少的切口浮肿，和更少不利事件。在裂开，或 hematoma 的发生的 CC 和 DCSD 组之间没有差别。这元分析的结果显示 DCSD 看起来比 CC 更安全、更有效。然而，有更大的学习人口的另外的高质量的 RCT 被需要。

Involvement of macrophage migration inhibitory factor in pathogenesis of atrial fibrillation as a redox-sensitive cytokine

Background Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine that controls inflammatory processes,and inflammation is known to play an important role in the pathogenesis of atrial fibrillation(AF).The present study sought to investigate whether MIF played an important role in the pathogenesis of AF.Methods MIF protein and mRNA levels in specimens of human right atrial appendage(from patients with AF or sinus rhythm)or atrium myocytes(HL-1 cells)were assayed using enzyme-linked immunosorbent assay(ELISA),real time PCR and Western blot,respectively.Results MIF expression levels were increased in AF when compared to SR.In cultured HL-1 cells,significant amounts of MIF were produced in response to hydrogen peroxide(H2O2).H2O2-induced MIF production increased in a dose-dependent manner and was completely abolished in the presence of catalase.The H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitor genistein and PP1.Conclusions These results implicate MIF might be involved in the pathogensis of AF as a redox-sensitive cytokine.[S Chin J Cardiol 2011;12(3):178-186]

Construction of bio-functional Mg/HA composite layered coating for orthopedic application

Magnesium was considered as a revolutionary biodegradable implant material for orthopedic application. Concerning the weakness of intrinsic strength and corrosion behavior, a novel strategy of Mg/metal hybrid system was proposed for extension of orthopedic application, especially at load-bearing site. In this work, an Mg and HA composite layered coating was constructed on titanium by means of chemical conversion and vapor deposition. The HA transition interlayer was introduced to enhance the bonding between Mg film and Ti substrate. Compared with the bare Mg coating, the Mg/HA coating presented good interface bonding, which avoided the occurrence of Mg film peeling off from the substrate. The Mg/HA coating showed a uniform degradation and kept integrity after immersion of 14 d. The Mg ions release by degradation played a crucial role in osteopromotion and antibacterial effect. Incubation of MC3T3-E1 osteoblasts with the Mg/HA coating showed significant promotion on osteogenic differentiation according to ALP activity and Alizarin Red staining assays. Meanwhile the degradation of Mg exhibited strong suppression of bacteria proliferation. It was believed that this novel Mg/HA composite layered coating could be potentially applied in further development of bio-functional hybrid orthopedic implants.