辛味中药在治疗消渴证中的应用价值及中药五味理论现代研究的思考

辛味是中药五味学说中的重要性味之一,通常具有“发散”“行气”和“行血”的作用,且辛味中药在传统医学临床应用中占有较大比例。结合中药辛味的功效内涵及传统中医理论对消渴证的认识,阐述辛味中药与消渴证治疗之间的内在联系,总结辛味中药对“消渴三消”的治疗意义与价值。并在此基础上,对中药五味理论的现代研究趋势和发展方向进行思考,为同行研究提供参考。     

行为-结构化-关系干预模式对短期住院孤独症谱系障碍儿童的疗效分析

目的 探讨以行为-结构化-关系(BSR)干预模式对短期住院孤独症谱系障碍(ASD)儿童的干预疗效,为改善ASD儿童的预后提供参考依据。方法 选取2015年12月－2016年12月确诊为ASD的2~6岁儿童141例,随机分为治疗组和对照组。治疗组ASD儿童均接受BSR模式的短期课程训练,训练课程包括个别辅导、游戏课、运动课、音乐课等,每天训练时间6 h,持续1个月;对照组ASD儿童处于干预等待,接受随访观察和评估。所有ASD儿童干预前、后均接受儿童心理教育评估(第三版)(PEP-3)来进行各方面能力变化的评估。结果 治疗组、对照组干预前各副测验的原积分差异无统计学意义(P>0.05)。两组ASD儿童干预后认知、语言理解、模仿、情感表达、社会互动、行为特征-非语言、适应行为的原积分比较,差异均有统计学意义(t=2.41、2.02、4.14、3.69、4.42、2.69、2.96,P<0.05);但小肌肉、大肌肉、自理的原积分比较,差异无统计学意义(t=-1.13、-1.05、-0.84,P>0.05)。结论 BSR干预模式能够有效改善短期住院ASD儿童的预后,可推广用于儿童ASD的治疗。     

Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

TcVac1 vaccine delivery by intradermal electroporation enhances vaccine induced immune protection against Trypanosoma cruzi infection in mice

The efforts for the development and testing of vaccines against Trypanosoma cruzi infection have increased during the past years. We have designed a TcVac series of vaccines composed of T. cruzi derived, GPI-anchored membrane antigens. The TcVac vaccines have been shown to elicit humoral and cellular mediated immune responses and provide significant (but not complete) control of experimental infection in mice and dogs. Herein, we aimed to test two immunization protocols for the delivery of DNA-prime/DNA-boost vaccine (TcVac1) composed of TcG2 and TcG4 antigens in a BALB/c mouse model. Mice were immunized with TcVac1 through intradermal/electroporation (IDE) or intramuscular (IM) routes, challenged with T. cruzi, and evaluated during acute phase of infection. The humoral immune response was evaluated through the assessment of anti-TcG2 and anti-TcG4 IgG subtypes by using an ELISA. Cellular immune response was assessed through a lymphocyte proliferation assay. Finally, clinical and morphopathological aspects were evaluated for all experimental animals. Our results demonstrated that when comparing TcVac1 IDE delivery vs IM delivery, the former induced significantly higher level of antigen-specific antibody response (IgG2a?+?IgG2b?>?IgG1) and lymphocyte proliferation, which expanded in response to challenge infection. Histological evaluation after challenge infection showed infiltration of inflammatory cells (macrophages and lymphocytes) in the heart and skeletal tissue of all infected mice. However, the largest increase in inflammatory infiltrate was observed in TcVac1_IDE/Tc mice when compared with TcVac1_IM/Tc or non-vaccinated/infected mice. The extent of tissue inflammatory infiltrate was directly associated with the control of tissue amastigote nests in vaccinated/infected (vs. non-vaccinated/infected) mice. Our results suggest that IDE delivery improves the protective efficacy of TcVac1 vaccine against T. cruzi infection in mice when compared with IM delivery of the vaccine.     

Penalized variable selection for accelerated failure time models with random effects

Accelerated failure time (AFT) models allowing for random effects are linear mixed models under the log-transformation of survival time with censoring and describe dependence in correlated survival data. It is well known that the AFT models are useful alternatives to frailty models. To the best of our knowledge, however, there is no literature on variable selection methods for such AFT models. In this paper, we propose a simple but unified variable-selection procedure of fixed effects in the AFT random-effect models using penalized h-likelihood (HL). We consider four penalty functions (ie, least absolute shrinkage and selection operator (LASSO), adaptive LASSO, smoothly clipped absolute deviation (SCAD), and HL). We show that the proposed method can be easily implemented via a slight modification to existing h-likelihood estimation procedures. We thus demonstrate that the proposed method can also be easily extended to AFT models with multilevel (or nested) structures. Simulation studies also show that the procedure using the adaptive LASSO, SCAD, or HL penalty performs well. In particular, we find via the simulation results that the variable selection method with HL penalty provides a higher probability of choosing the true model than other three methods. The usefulness of the new method is illustrated using two actual datasets from multicenter clinical trials.     

Impact of vaccination delay on deaths averted by pneumococcal conjugate vaccine: Modeled effects in 8 country scenarios

Delay in vaccination from schedule has been frequently documented and varies by vaccine, dose, and setting. Vaccination delay may result in the failure to prevent deaths that would have been averted by on-schedule vaccination.We constructed a model to assess the impact of delay in vaccination with pneumococcal conjugate vaccine (PCV) on under-five mortality. The model accounted for the week of age-specific risk of pneumococcal mortality, direct effect of vaccination, and herd protection. For each model run, a cohort of children were exposed to the risk of mortality and protective effect of PCV for each week of age from birth to age five. The model was run with and without vaccination delay and difference in number of deaths averted was calculated. We applied the model to eight country-specific vaccination scenarios, reflecting variations in observed vaccination delay, PCV coverage, herd effect, mortality risk, and vaccination schedule. As PCV is currently being scaled up in India, we additionally evaluated the impact of vaccination delay in India under various delay scenarios and coverage levels.We found deaths averted by PCV with and without delay to be comparable in all of the country scenarios when accounting for herd protection. In India, the greatest relative difference in deaths averted was observed at low coverage levels and greatest absolute difference was observed around 60% vaccination coverage. Under moderate delay scenarios, vaccination delay had modest impact on deaths averted by PCV in India across levels of coverage or vaccination schedule. Without accounting for herd protection, vaccination delay resulted in much greater failure to avert deaths.Our model suggests that realistic vaccination delay has a minimal impact on the number of deaths averted by PCV when accounting for herd effect. High population coverage can largely over-ride the deleterious effect of vaccination delay through herd protection.     

Using a monotone single-index model to stabilize the propensity score in missing data problems and causal inference

The augmented inverse weighting method is one of the most popular methods for estimating the mean of the response in causal inference and missing data problems. An important component of this method is the propensity score. Popular parametric models for the propensity score include the logistic, probit, and complementary log-log models. A common feature of these models is that the propensity score is a monotonic function of a linear combination of the explanatory variables. To avoid the need to choose a model, we model the propensity score via a semiparametric single-index model, in which the score is an unknown monotonic nondecreasing function of the given single index. Under this new model, the augmented inverse weighting estimator (AIWE) of the mean of the response is asymptotically linear, semiparametrically efficient, and more robust than existing estimators. Moreover, we have made a surprising observation. The inverse probability weighting and AIWEs based on a correctly specified parametric model may have worse performance than their counterparts based on a nonparametric model. A heuristic explanation of this phenomenon is provided. A real-data example is used to illustrate the proposed methods.     

深圳市龙岗区大气污染物与医院呼吸系统疾病门诊量的广义相加模型分析

目的 探讨深圳市龙岗区主要大气污染物(SO₂、NO₂、PM₁₀与PM_2.5)与医院呼吸系统疾病门诊量的关系。 方法 收集2013年1月1日－2015年12月31日深圳市龙岗区2家公立医院呼吸系统疾病逐日门诊量资料,深圳市龙岗区逐日大气污染物浓度及逐日气象资料分别来自深圳市环境监测站及气象局,运用时间序列分析广义相加模型对大气污染物日均浓度与呼吸系统疾病门诊量的关系及滞后效应进行分析。 结果 深圳市龙岗区2013－2015年SO₂ 、NO₂ 、PM₁₀ 与PM_2.5浓度中位数分别为8.08、38.08、46.05 μg/m³及31.04 μg/m³。2家医院三年呼吸系统门诊总量为549 169人次,日门诊量中位数为499人次/d。广义相加模型分析结果表明,除NO₂对呼吸系统疾病门诊量影响差异无统计学意义外,其余三种污染物对呼吸系统疾病门诊量影响均存在滞后效应,污染物每升高10 μg/m³,滞后2 d时SO₂对门诊量影响最强(相对危险度RR为1.030 7,95%CI:1.015 7~1.045 9),滞后3 d时PM₁₀与PM_2.5浓度对呼吸系统疾病门诊量影响最强(PM₁₀:RR=1.005 4,95%CI:1.002 8~1.008 0,PM_2.5:RR=1.006 0, 95%CI:1.002 7~1.009 4)。 结论 深圳市龙岗区大气SO₂、PM₁₀与PM_2.5浓度对医院呼吸系统疾病门诊量影响存在滞后效应。