手术切除与介入栓塞治疗肝癌术后复发患者的临床对比研究

目的:比较手术切除与介入栓塞治疗肝癌术后复发患者的临床疗效。方法:选择2010年6月到2011年6月本院收治的92例肝癌手术切除术后复发患者,按随机数字表法分为手术切除组和介入栓塞组,各46例。手术切除组患者给予再次切除治疗,介入栓塞组患者给予介入栓塞治疗。记录并比较两组患者治疗后1年、3年及5年的生存率。检测并比较两组患者治疗前后血清肝纤维化指标,包括血清透明质酸(HA)、层黏蛋白(LN)、人Ⅲ型前胶原(HPC-Ⅲ)及IV型胶原(IV-C)水平。检测并比较两组患者治疗前后血清白细胞(WBC)、甲胎蛋白(AFP)及癌胚抗原(CEA)水平。结果:手术切除组患者治疗后1年、3年、5年的生存率均明显高于介入栓塞组,差异均具有统计学意义(P0.05)。治疗后,介入栓塞组血清HA、LN、HPC-Ⅲ及IV-C明显高于治疗前,且均明显高于手术切除组,差异均具有统计学意义(P0.05)。两组患者治疗后血清WBC、AFP及CEA水平均明显低于治疗前,且手术切除组患者血清WBC明显高于介入栓塞组,而血清AFP、CEA水平明显低于介入栓塞组,差异均具有统计学意义(P0.05)。结论:手术切除治疗肝癌术后复发能够明显提高患者生存率,降低肝纤维化程度,改善血清AFP及CEA水平,值得在临床上推广应用。     

Emergence of network structure due to spike-timing-dependent plasticity in recurrent neuronal networks. II. Input selectivity—symmetry breaking

Spike-timing-dependent plasticity (STDP) is believed to structure neuronal networks by slowly changing the strengths (or weights) of the synaptic connections between neurons depending upon their spiking activity, which in turn modifies the neuronal firing dynamics. In this paper, we investigate the change in synaptic weights induced by STDP in a recurrently connected network in which the input weights are plastic but the recurrent weights are fixed. The inputs are divided into two pools with identical constant firing rates and equal within-pool spike-time correlations, but with no between-pool correlations. Our analysis uses the Poisson neuron model in order to predict the evolution of the input synaptic weights and focuses on the asymptotic weight distribution that emerges due to STDP. The learning dynamics induces a symmetry breaking for the individual neurons, namely for sufficiently strong within-pool spike-time correlation each neuron specializes to one of the input pools. We show that the presence of fixed excitatory recurrent connections between neurons induces a group symmetry-breaking effect, in which neurons tend to specialize to the same input pool. Consequently STDP generates a functional structure on the input connections of the network.     

Emergence of network structure due to spike-timing-dependent plasticity in recurrent neuronal networks. I. Input selectivity–strengthening correlated input pathways

Spike-timing-dependent plasticity (STDP) determines the evolution of the synaptic weights according to their pre- and post-synaptic activity, which in turn changes the neuronal activity. In this paper, we extend previous studies of input selectivity induced by (STDP) for single neurons to the biologically interesting case of a neuronal network with fixed recurrent connections and plastic connections from external pools of input neurons. We use a theoretical framework based on the Poisson neuron model to analytically describe the network dynamics (firing rates and spike-time correlations) and thus the evolution of the synaptic weights. This framework incorporates the time course of the post-synaptic potentials and synaptic delays. Our analysis focuses on the asymptotic states of a network stimulated by two homogeneous pools of “steady” inputs, namely Poisson spike trains which have fixed firing rates and spike-time correlations. The (STDP) model extends rate-based learning in that it can implement, at the same time, both a stabilization of the individual neuron firing rates and a slower weight specialization depending on the input spike-time correlations. When one input pathway has stronger within-pool correlations, the resulting synaptic dynamics induced by (STDP) are shown to be similar to those arising in the case of a purely feed-forward network: the weights from the more correlated inputs are potentiated at the expense of the remaining input connections.     

Smoothing spline ANOVA frailty model for recurrent event data

Gap time hazard estimation is of particular interest in recurrent event data. This article proposes a fully nonparametric approach for estimating the gap time hazard. Smoothing spline analysis of variance (ANOVA) decompositions are used to model the log gap time hazard as a joint function of gap time and covariates, and general frailty is introduced to account for between-subject heterogeneity and within-subject correlation. We estimate the nonparametric gap time hazard function and parameters in the frailty distribution using a combination of the Newton-Raphson procedure, the stochastic approximation algorithm (SAA), and the Markov chain Monte Carlo (MCMC) method. The convergence of the algorithm is guaranteed by decreasing the step size of parameter update and/or increasing the MCMC sample size along iterations. Model selection procedure is also developed to identify negligible components in a functional ANOVA decomposition of the log gap time hazard. We evaluate the proposed methods with simulation studies and illustrate its use through the analysis of bladder tumor data.     

A semiparametric estimator of the bivariate distribution function for censored gap times

Let (T(1), T(2)) be gap times corresponding to two consecutive events, which are observed subject to random right-censoring. In this paper, a semiparametric estimator of the bivariate distribution function of (T(1), T(2)) and, more generally, of a functional E [φ(T(1),T(2))] is proposed. We assume that the probability of censoring for T(2) given the (possibly censored) gap times belongs to a parametric family of binary regression curves. We investigate the conditions under which the introduced estimator is consistent. We explore the finite sample behavior of the estimator and of its bootstrap standard error through simulations. The main conclusion of this paper is that the semiparametric estimator may be much more efficient than purely nonparametric methods. Real data illustration is included.     

匹多莫德对反复呼吸道感染患儿外周血T淋巴细胞亚群变化的影响及其临床疗效

目的:研究匹多莫德治疗反复呼吸道感染患儿的临床疗效,并探讨其对患儿外周血T淋巴细胞亚群变化的影响。方法:选择我院收治的160例反复呼吸道感染患儿,根据临床治疗方法将其分成研究组(80例)与对照组(80例),对照组采用抗生素或抗病毒、退热、止咳、平喘与化痰等对症治疗,研究组则在对照组的基础上再加用匹多莫德口服。比较两组患儿外周血T淋巴细胞亚群变化并分析其临床疗效。结果:研究组治疗总有效率显著优于对照组(P0.05)。研究组治疗后CD3+、CD4+、CD4+/CD8+水平,与治疗前比较明显升高(P0.05),与对照组同期比较具有明显的差异(P0.05)。研究组患儿治疗后白细胞计数及中性粒细胞水平,与治疗前比较无明显差异(P0.05),与对照组同期比较无明显差异(P0.05);对照组治疗前后白细胞计数及中性粒细胞水平无明显差异(P0.05)。研究组患儿咳嗽、发热、喘息、肺部啰音消失时间以及抗生素使用时间均明显少于对照组(P0.01)。研究组与对照组患儿治疗过程中均未发生明显的药物不良反应。结论:匹多莫德治疗反复呼吸道感染患儿疗效确切,能有效改善T淋巴细胞的免疫功能,值得临床推广与应用。     

二次肿瘤细胞减灭术在铂类敏感的复发性卵巢上皮癌中的作用

目的:探讨二次肿瘤细胞减灭术对铂类敏感的复发性卵巢上皮癌治疗的临床意义。方法:回顾性分析我院于2002年1月至2012年12月收治的115例铂类敏感的复发性卵巢上皮癌患者的临床及随访资料。结果:在115例铂类敏感的复发性卵巢上皮癌中,66例接受了二次肿瘤细胞减灭术(手术组),术后辅以铂类为基础的化疗。49例患者只接受了以铂类为基础的化疗(对照组)。两组患者肿瘤病理分型无统计学差异(P=0.485)。与对照组相比,手术组FIGO分期IV期患者的比例少(15.2%VS 34.7%,P=0.014),低分化患者的比例少(71.2%VS 91.8%,P=0.024),多发复发病灶患者的比例少(28.3%VS 49.0%,P=0.027)。平均随访30.2个月(6-48个月),Kaplan-Meier生存分析显示,手术组与对照组患者的中位生存期分别为35.0个月和27.0个月,差异有统计学差异(Log rank 7.9,P=0.005)。多因素Cox回归分析显示,校正了年龄、肿瘤病理类型、病理分级及FIGO分期后,不同治疗方案是复发上皮性卵巢癌患者远期生存率的独立影响因素。结论:二次肿瘤细胞减灭术可以改善铂类敏感的复发性卵巢上皮癌患者的临床预后。     

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill¹.Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone². This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting^3-5. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab⁶. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis⁷. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients^8,9. Bevacizumab however failed to prolong overall survival in a recent phase III trial²⁶. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians’ choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm¹⁰.There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy^11,12, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.     

Recurrent production of plants of black plum, Syzygium cuminii (L.) Skeels, a myrtaceous fruit tree, from in vitro cultured seedling explants

 The epicotyl segments bearing scaly leave(s), excised from in vitro grown seedlings of Syzygium cuminii, produced multiple shoots when cultivated on Murashige and Skoog's (MS, 1962) medium supplemented with different concentrations of BA (0–2 mg l^–1). The optimum response was recorded on the medium containing 1 mg l^–1 BA. An average of 8.6 shoots per explant were produced 60 days after inoculation, following transfer to fresh medium after 30 days. The shoots were excised, and the residual explants were transferred to fresh medium, where they again developed shoots. Up to five such passages resulted in the production of shoots from the repeatedly subcultured original explants. However, during the fifth passage, organogenic response was negligible and the explants turned brown thereafter. Following repeated harvesting of shoots and subculture of the residual explants, an average of 29 shoots per explant was obtained. The in vitro developed shoots produced roots when transferred to Knop's medium supplemented with 2% sucrose and 1 mg l^–1 IAA. The developed plantlets were planted in soil and transferred to fields after an acclimatization period of 7–8 months. These plants have been thriving well for more than 3 years. The nodal explants excised from in vitro developed shoots and plants also exhibited a similar response when cultured on MS+1 mg l^–1 BA. Thus, a protocol has been developed to raise plants of S. cuminii at any time of the year. Received: 1 December 1998 / Revision received: 1 July 1999 · Accepted: 12 July 1999     

动脉插管化疗配合膀胱灌注治疗复发性、多发性、表浅性膀胱癌

目的:探讨腹壁下动脉插管化疗(inferior-epigastric artery chemotherapy,IAC)配合吡柔比星(THP)膀胱灌注治疗复发性、多发性和表浅性膀胱癌的疗效。方法:对12例复发性、多发性和表浅性膀胱移行细胞癌患者术后行腹壁下动脉插管化疗3个疗程后,开始行吡柔比星膀胱灌注,每次30 mg,每周1次共12次,以后每2周1次共6次,以后每月1次共6次,第二年重复,第三年每月一次。定期膀胱镜检查,进行随访。结果:12例复发性、多发性、浅表性膀胱移行细胞癌患者,术后随访时间24-48个月,肿瘤复发1例,复发率8.3%。不良反应主要为术后小膀胱,尿路刺激症状和尿常规异常。结论:腹壁下动脉插管化疗配合吡柔比星膀胱灌注治疗复发性、多发性和表浅性膀胱癌的效果明确,疗效满意,患者耐受性好,值得临床推广应用。