Sufficient dimension reduction on the mean and rate functions of recurrent events

The counting process with a Cox‐type intensity function has been extensively applied to analyze recurrent event data, which assume that the underlying counting process is a time‐transformed Poisson process and that the covariates have multiplicative or additive effects on the mean and rate functions of the counting process. The existing statistical inference, however, often encounters difficulties due to high‐dimensional covariates, such as in gene expression and single nucleotide polymorphism data that have revolutionized our understanding of cancer recurrence and other diseases. In this paper, a technique of sufficient dimension reduction is applied to the mean and rate function for the number of occurrences of events over time. A two‐step procedure is proposed to estimate the model components: first, a nonparametric estimator is proposed for the baseline, and then the basis of the central subspace and its dimension are estimated through a modified slicing inverse regression. On the basis of the estimated structural dimension and on the basis of the central subspace, we can estimate the regression function by using the local linear regression. A simulation is performed to confirm and assess the theoretical findings, and an application is demonstrated on a set of chronic granulomatous disease data. Copyright © 2014 John Wiley & Sons, Ltd.     

Techniques,indications and complications of corneal debridement

The cornea is the most exposed surface of the eye and, as such, is vulnerable to external trauma and the risk of infection. Many corneal diseases alter shape, surface, and transparency and thus result in reduced vision. The external position of the cornea, however, lends itself to diagnostic and therapeutic maneuvers that are commonly performed and readily done in the clinic. More sophisticated techniques require the use of complex equipment such as excimer and femtosecond laser. Complications that develop from poor healing and/or secondary infection are best avoided with appropriate technique, antisepsis, and modification of wound healing. We review corneal debridement in the management of corneal disease.     

扶正抗感膏方配合耳穴贴压法治疗反复呼吸道感染32例患儿临床观察

目的:探讨扶正抗感膏方配合耳穴贴压法治疗小儿反复呼吸道感染(RRTI)缓解期(肺脾气虚证)的临床疗效及对免疫功能及血清微量元素变化的影响。方法:将64例患儿随机分为治疗组和对照组各32例,治疗组采用口服扶正抗感膏方配合双侧耳穴贴压法治疗,对照组给予转移因子口服液口服,两组均以8周为一个疗程,疗程结束后均随访1年。比较分析两组总疗效,检测治疗前后IgG、IgM、IgA及血清锌、铁、铜水平的变化情况。结果:治疗组总有效率为93.3%,对照组为68.9%;两组比较具有统计学意义(P<0.05);与治疗前及对照组相比,治疗组IgG、IgA、血锌、血铁水平均升高,具有统计学意义(P<0.05和P<0.01)。结论:扶正抗感膏方配合耳穴贴压法对肺脾气虚型小儿RRTI临床疗效显著,其机制与该疗法有效调节免疫功能、纠正锌等微量元素失衡有关。     

寿胎丸对脂多糖诱导的人绒毛外滋养细胞氧化应激及焦亡的调节作用

目的 探讨寿胎丸在脂多糖（LPS）诱导的人绒毛外滋养细胞（HTR-8/SVneo）损伤中的作用及其对细胞损伤中氧化应激和焦亡的调控，为寿胎丸安胎的作用机制研究提供新的方向。方法 采用LPS（100 μg?L^-1）诱导HTR-8/SVneo细胞损伤建立细胞模型，设置空白组、模型组、寿胎丸组（10%寿胎丸含药血清）、抗氧化剂组（1 mmol·L^-1 NAC）、NOD样受体热蛋白结构域3（NLRP3）抑制剂组（50 μmol·L^-1MCC950）。分别采用细胞增殖与活性检测（CCK-8）试剂盒检测细胞活性情况；Hochest 33342/PI双荧光染色和流式细胞术观察细胞死亡情况；酶联免疫吸附测定法（ELISA）检测细胞上清液中白细胞介素-18（IL-18）、白细胞介素-1β（IL-1β）、丙二醛（MDA）、超氧化物歧化酶（SOD）释放情况；DCFH-DA探针检测细胞内活性氧（ROS）含量；蛋白免疫印迹法（Western blot）检测NLRP3、胱天蛋白酶（Caspase）-1、消化道皮肤素D（GSDMD）、IL-1β蛋白的表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测NLRP3、Caspase-1 mRNA的表达。结果 与空白组比较，模型组细胞活力显著降低（P<0.01），细胞上清液中炎症因子IL-1β、IL-18含量显著增加（P<0.01），氧化应激因子ROS、MDA含量升高，SOD活性显著降低（P<0.01），NLRP3、Caspase-1、GSDMD、IL-1β蛋白和NLRP3、Caspase-1 mRNA表达显著上调（P<0.01）；与模型组比较，寿胎丸组、NAC组及MCC950组细胞活力显著升高（P<0.01），寿胎丸组和NAC组MDA、ROS活性降低，SOD活性显著升高（P<0.01），寿胎丸组和MCC950组细胞上清液中IL-1β、IL-18含量减少（P<0.01），细胞内NLRP3、Caspase-1、GSDMD、IL-1β蛋白和NLRP3、Caspase-1、IL-1β mRNA表达均明显降低（P<0.05，P<0.01）。结论 寿胎丸可通过抑制氧化应激和细胞焦亡减轻LPS诱导的HTR-8/SVneo细胞损伤，这可能是寿胎丸防治复发性流产，发挥安胎作用的机制之一。     

Description of two new ABCB11 mutations responsible for type 2 benign recurrent intrahepatic cholestasis in a French-Canadian family

Benign recurrent intrahepatic cholestasis is a rare clinical entity that is caused by mutations in the canalicular transport genes. The present report describes two individuals from the same family whose symptoms were typical of the clinical characteristics of type 2 benign recurrent intrahepatic cholestasis. Sequencing of the ABCB11 gene revealed two previously unreported mutations that predict the absence of expression of the protein. The clinical presentation of the current cases are discussed, as are the differential diagnosis and genetic characteristics of the hereditary cholestatic disorders, overemphasizing the possibility of making a definite genetic diagnosis.     

甲状腺癌术后复发再手术中甲状旁腺和神经保护

甲状腺癌是一种十分常见的恶性肿瘤，其病理类型大多数为分化型甲状腺癌，经规范化治疗，预后较好，但仍有部分病人复发，且长期随访，可有高达30%以上的复发或转移率。因此，再次手术是甲状腺外科医师不可避免的问题，甚至在未来一段时间会成为一个临床常见情况。再次手术，尤其是Ⅵ区淋巴结复发的再次手术，往往有较高的手术难度和风险，需要谨慎地选择手术时机和入路，术中应用神经监测与传统显露技术相结合以保护喉返神经，运用传统识别和保护手法，选择性应用纳米炭、甲状旁腺素试纸、近红外自体荧光显像等技术以保护甲状旁腺功能。     

Dendrites,deep learning,and sequences in the hippocampus

The hippocampus places us both in time and space. It does so over remarkably large spans: milliseconds to years, and centimeters to kilometers. This works for sensory representations, for memory, and for behavioral context. How does it fit in such wide ranges of time and space scales, and keep order among the many dimensions of stimulus context? A key organizing principle for a wide sweep of scales and stimulus dimensions is that of order in time, or sequences. Sequences of neuronal activity are ubiquitous in sensory processing, in motor control, in planning actions, and in memory. Against this strong evidence for the phenomenon, there are currently more models than definite experiments about how the brain generates ordered activity. The flip side of sequence generation is discrimination. Discrimination of sequences has been extensively studied at the behavioral, systems, and modeling level, but again physiological mechanisms are fewer. It is against this backdrop that I discuss two recent developments in neural sequence computation, that at face value share little beyond the label “neural.” These are dendritic sequence discrimination, and deep learning. One derives from channel physiology and molecular signaling, the other from applied neural network theory ‐ apparently extreme ends of the spectrum of neural circuit detail. I suggest that each of these topics has deep lessons about the possible mechanisms, scales, and capabilities of hippocampal sequence computation.     

Recurrent oral squamous cell carcinoma‐incorporating advance care planning in education and practice

This reflection describes a life‐limiting case of oral squamous cell carcinoma (SCC) that required thoughtful management facilitated by an advance care plan (ACP). A 70‐year‐old female was diagnosed with a T4aN2bM0 biopsy‐proven invasive, well‐differentiated keratinizing SCC. Surgical wide‐local excision included teeth #11‐16 with left unilateral neck dissection, levels I‐V. She was rehabilitated with maxillary obturator prosthesis and underwent chemoradiation therapy. Her course was complicated by dysphagia and trismus. She experienced multiple recurrences. At a certain point, negative margins could not be achieved without facial disfigurement. The patient, her husband, and providers decided together that further management would be palliative. Before the additional surgical procedures, she communicated a thorough ACP with her husband and providers who were prepared to facilitate difficult care decisions on her behalf. The patient passed away at home with hospice care at the age of 74. This motivated patient with oral SCC and impactful postmanagement complications appreciated the clarity of an ACP. Her values and goals of care were incorporated with ongoing communication and documentation of this plan, which was instrumental in facilitating her person‐centered care. The providers apply lessons learned here in future practice and education of residents and students.