Circadian Rhythmicity as a Predictor of Quality of Life in Allogeneic Hematopoietic Cell Transplant Patients

Context

Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.

临床药师对垂体瘤卒中合并哮喘患者的术后药学监护

摘 要本文介绍1例有哮喘病史的患者行经蝶垂体瘤切除术后哮喘加重的案例。临床药师根据垂体瘤卒中急症特征及氢化可的松药动学特点，为患者制定了个体化的糖皮质激素替代治疗方案。在患者出现明显哮喘症状时及时调整糖皮质激素和支气管扩张剂。使用低剂量的右美托咪定适当镇静改善患者烦躁，避免患者自主呼吸与呼吸机对抗导致哮喘治疗不佳。治疗过程中，临床药师协助医师根据患者情况及时调整治疗方案，充分体现了临床药师在外科围手术期患者药物治疗管理中的价值。     

Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment

Stem cell transplantation has brought new hope for the treatment of neurological diseases.The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells.Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors,the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located.Accordingly,the optimal microenvironment for inducing stem cell differentiation is a hot topic.EGb761 is extracted from the leaves of the Ginkgo biloba tree.It is used worldwide and is becoming one of the focuses of stem cell research.Studies have shown that EGb761 can antagonize oxygen free radicals,stabilize cell membranes,promote neurogenesis and synaptogenesis,increase the level of brain-derived neurotrophic factors,and replicate the environment required during the differentiation of stem cells into nerve cells.This offers the possibility of using EGb761 to induce the differentiation of stem cells,facilitating stem cell transplantation.To provide a comprehensive reference for the future application of EGb761 in stem cell therapy,we reviewed studies investigating the influence of EGb761 on stem cells.These started with the composition and neuropharmacology of EGb761,and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation.     

Exercise training‐induced visceral fat loss in obese women: The role of training intensity and modality

Visceral fat loss in response to four‐cycle ergometer training regimens with explicit differences in exercise intensity and modality was compared. Fifty‐nine obese young women (body fat percentage ≥ 30%) were randomized to a 12‐week intervention consisting of either all‐out sprint interval training (SIT_all‐out, n = 11); supramaximal SIT (SIT₁₂₀, 120% O_2peak, n = 12); high‐intensity interval training (HIIT₉₀, 90% O_2peak, n = 12), moderate‐intensity continuous training (MICT, 60% O_2peak, n = 11), or no training (CON, n = 13). The total work done per training session in SIT₁₂₀, HIIT₉₀, and MICT was confined to 200 kJ, while it was deliberately lower in SIT_all‐out. The abdominal visceral fat area (AVFA) was measured through computed tomography scans. The whole‐body and regional fat mass were assessed through dual‐energy X‐ray absorptiometry. Pre‐, post‐, and 3‐hour post‐exercise serum growth hormone (GH), and epinephrine (EPI) were measured during selected training sessions. Following the intervention, similar reductions in whole‐body and regional fat mass were found in all intervention groups, while the reductions in AVFA resulting from SIT_all‐out, SIT₁₂₀, and HIIT₉₀ (>15 cm²) were greater in comparison with MICT (<3.5 cm², P < .05). The AVFA reductions among the SITs and HIIT groups were similar, and it was concomitant with the similar exercise‐induced releases of serum GH and EPI. CON variables were unchanged. These findings suggest that visceral fat loss induced by interval training at or above 90% O_2peak appeared unresponsive to the change in training intensity. Nonetheless, SIT_all‐out is still the most time‐efficient strategy among the four exercise‐training regimes for controlling visceral obesity.     

一日四时的临床运用

以一日四时人体阴阳的变化,即在不同的时间里人体的生理功能活动和在病理情况下"夫百病者,多以旦慧昼安,夕加夜甚"(《灵枢·顺气一日分为四时》)来论述因时制宜的重要性.本文仅肤浅地分析因时制宜并提出一日四时的治疗用药原则,又介绍了阳气虚证和阴虚盗汗证的治疗经验,对临床工作具有实用价值.     

苏东坡与圣散子方

圣散子为中医抗疫之名方,不仅因为其卓著的疗效,更有赖于一代文豪苏东坡的大力推荐.然而此方在流传的过程中,却出现了不少问题,甚则"杀人无数".本为疗寒疫之方,而用之于热疫,其中的原因值得深思.     

肺癌合并慢性阻塞性肺疾病外科治疗的肺功能评价

目的评价慢性阻塞性肺疾病(COPD)患者合并肺癌行肺叶切除的手术风险和手术对肺功能的影响.方法回顾分析1998年1月至2005年1月我院收治的中度COPD合并周围型非小细胞肺癌32例患者的临床资料.其中,男29例,女3例;平均年龄(65.0±5.4)岁.病理分型:鳞癌2l例,腺癌11例;病理分期:Ⅰ期2例,Ⅱ期5例,Ⅲa期24例,Ⅲb期l例.所有患者均接受肺叶切除术.结果术前患者肺功能第1秒用力呼吸容积(FEV1)和动脉氧分压平均值分别为(64±9)%和(85±12)mmHg,术后分别为(62±10)%和(87±11)mmHg,虽然FEV1略有下降,但均无显著性差异(P＞0.05).本组无围手术期死亡者.结论中度COPD患者仍有一定的肺功能储备,可耐受肺叶切除手术.     

A Physiologically Based Pharmacokinetic Modeling Approach to Predict Drug-Drug Interactions of Buprenorphine After Subcutaneous Administration of CAM2038 With Perpetrators of CYP3A4

CAM2038, FluidCrystal injection depot, is an extended release formulation of buprenorphine given subcutaneously every 1 week (Q1W) or every 4 weeks (Q4W). The purpose of this research was to predict the magnitude of drug-drug interaction (DDI) after coadministration of a strong CYP3A4 inducer or inhibitor using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model was developed for CAM2038 based on the previously published buprenorphine PBPK model after intravenous and sublingual administration and the PK profiles after subcutaneous administration of CAM2038 from 2 phase I clinical trials. The strong CYP3A4 inhibitor ketoconazole was predicted to increase the buprenorphine exposure by 35% for the Q1W formulation and 34% for Q4W formulation, respectively. Also, the strong CYP3A4 inducer rifampin was predicted to decrease the buprenorphine exposure by 26% for both the Q1W and Q4W formulations. The results provided insight into the potential DDI effect for CAM2038 and suggested a lack of clinically meaningful DDI when CAM2038 is coadministered with CYP3A4 inhibitor or inducer. Therefore, no dose adjustment is required when CAM2038 is coadministered with CYP3A4 perpetrators.     

A Mathematical Model and Experimental Verification of Optimal Nozzle Diameter in Needle-Free Injection

Needle-free injection (NFI), as an alternative drug delivery strategy, owns great potential. It is able to reduce complaints about needle phobia and avoid the occurring of accidental needle stick injuries. The nozzle diameter is inherently important in determining the injection dose, injection depth, and pain associated with NFIs. In this work, needle-free injectors with nozzle diameters of 0.17, 0.20, 0.30, 0.40, and 0.50 mm were studied in the simulation and experiment. This article optimizes the mathematical model for spring-powered NFI by considering the hydraulic loss due to the abrupt change in the nozzle exit area and the friction force between the piston and ampoule. We explore the dispersion pattern in gels with different nozzle diameters. Mice insulin injection was conducted to investigate the pharmacological effect of different injection methods. The experimental results show that there is the best dispersion effect and available injection depth while the nozzle diameter is 0.30 mm, which is in agreement with the result predicted by the mathematical model. Also, there is a satisfactory pharmacological effect on the mice insulin injection under the same injection condition. Undoubtedly, the mathematical model is capable of predicting the suitable nozzle diameter under the given conditions.     

Exploring a Kinetic Model Approach in Biopharmaceutics: Estimating the Fraction Absorbed of Orally Administered Drugs in Humans

Increasing costs of research and development in the pharmaceutical industry has necessitated a growing interest in the early prediction of human pharmacokinetics of drug candidates. Of growing interest is the need to understand oral absorption, the most common route of small molecule drug administration. The fraction of dose absorbed (%Fa) is considered a critical yet challenging parameter to predict. A kinetic model has been developed and tested to provide an early prediction of the fraction dose absorbed in humans. Unlike the traditional plug-flow model, this model assumes first-order kinetics to estimate the amount of drug present in the stomach and small intestine as a function of time and calculates the amount of drug released and absorbed during the transit. Other variables can be included in calculation as a function of time to better mimic the physiological condition with this approach. Absorption efficiency is assigned along with %Fa to give a quantitative estimate of the limiting factor for oral absorption. The model was tested with literature and in-house compounds. It was found that this model gives a good prediction of human %Fa with a correction coefficient (R²) of 0.8 and greater between predicted and reported %Fa for all compounds.