腹腔镜下输卵管手术方式对卵巢储备功能的影响

目的：探讨腹腔镜下输卵管手术方式对卵巢储备功能的影响。方法：126例输卵管积水患者按手术方案分为A、B、C三组：A组     

Statins may ameliorate pulmonary hypertension via RhoA/Rho-kinase signaling pathway

Statins are the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that function as potent inhibitors of cholesterol biosynthesis and have been used for many years for the treatment of hypercholesterolemia. However, accumulating experimental and clinical studies have revealed that the health benefits associated with statins treatment, particularly those conferred on the cardiovascular system, were the cholesterol-independent. Because statins inhibit an early step in the cholesterol biosynthetic pathway, they also inhibit the synthesis of isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are important postranslational lipid attachments for intracellular signaling molecules such as the Rho GTPases. The isoprenylation of Rho is a prerequisite for Rho activation, facilitating its interaction with the plasma membrane, undergoing GDP-GTP exchange and be activated. Inhibition of RhoA geranylgeranylation by statins decreases membrane GTP-bound active RhoA and subsequent Rho-kinase activity. Activated RhoA via its downstream effector Rho-kinase is involved in a wide range of cellular functions, such as cell migration, proliferation and apoptosis. Recently, rising evidences suggested that RhoA/Rho-kinase pathway was essentially involved in various models of pulmonary hypertension and statins effectively ameliorated pulmonary hypertension. Based on this findings, we hypothesis that statins attenuate pulmonary hypertension via RhoA/Rho-kinase signaling pathway in vivo.     

Association of beta 2-adrenergic receptor polymorphism with the phenotype of aspirin-intolerant acute urticaria

The genetic mechanism of aspirin intolerant acute urticaria (AIAU) is unknown. To demonstrate an association between the beta 2 adrenergic receptor (ADRB2) polymorphism and the phenotype of AIAU, one hundred fourteen patients with AIAU, 110 patients with aspirin intolerant chronic urticaria (AICU), and 498 normal healthy controls (NC) based on a Korean population were enrolled. The genotype of ADRB2 at 46 A > G was analyzed using a direct sequencing method. The ADRB2 polymorphism at 46 A > G showed a significant difference between AIAU and NC; the frequency of the major genotype was significantly higher in the AIAU group (p= 0.017 in recessive model), while no differences were noted in allele and genotype frequencies between AICU and NC. In conclusion, the ADRB2 (46 A > G) gene polymorphism may contribute to the development of the phenotype of AIAU.     

Heroin impairs map-picture-following and memory tasks dependent on gender and orientation of the tasks

Male and female heroin-dependent patients (HDPs) matched with "normal" people were tested on 4 topographical orientation tasks: schematic map-following, map-memory, schematic picture-following, and picture-memory tasks. The results showed that, in general, female HDPs demonstrated greater performance deficits in map-following and map-picture-memory tasks than did other participants. In the map-picture-following tasks, participants showed a preference for turning right versus turning left, reflected by lower correct scores and longer latencies in completing left-oriented tasks. In contrast, no difference in orientation preference was found for participants in memory tasks, except for female HDPs. Asymmetric dopamine receptor distribution in the brain, sex steroidal hormone, brain areas related to motor functioning and working memory, and gender-dependent lateralization may be involved in the different effects of heroin and rightward bias between men and women.     

RhPDCD5 combined with dexamethasone increases antitumor activity in multiple myeloma partially via inhibiting the Wnt signalling pathway

Multiple myeloma (MM) is one of the most common hematological malignancies and characterized by the clonal accumulation of malignant plasma cells. Significant progress has been made in MM treatment recently, while MM still remains incurable. Our previous studies showed that the recombined human programmed cell death 5 (rhPDCD5) can promote MM apoptosis induced by dexamethasone (Dex). Here, we expanded the findings by showing that the rhPDCD5 alone could not induce an obvious growth inhibition of U266 cells (a MM cell line). Of note, with the combination of dexamethasone (Dex), the growth of MM cells was significantly inhibited and accompanied with the cell cycle arrest in G0/G1. For mechanism study, we found that the combination treatment of rhPDCD5 plus Dex downregulated the mRNA and protein expressions of Wnt effectors including β‐catenin, β‐catenin (Ser675), TCF4, survivin and c‐Myc when compared to Dex only. Moreover, the activation of WNT pathway induced by LiCl can also be inhibited by this combination treatment. Taken together, our study demonstrated that the combination of rhPDCD5 and Dex can suppress the proliferation of multiple myeloma cells partially via inhibiting the WNT signalling pathway.     

政府管制与取消管制对药品价格的影响研究——以消化类药品为例

目的:探究政府管制与取消管制对药品价格的影响,为药品定价政策制定提供依据。方法:研究提取全国医药经济信息网数据库中2011年1月-2016年6月64种消化类药品价格水平、用量和费用的月度数据,通过有对照的间断时间序列(interrupted time-series,ITS)模型,分别分析政府管制和取消管制后样本药品的价格水平、用量与费用变化,其中使用固定拉氏价格指数衡量药品价格水平。第一个ITS分析政府管制的影响,利用2011年1月-2015年6月的月度数据,间断点为2012年5月;第二个ITS分析取消管制的影响,利用2014年6月-2016年6月的月度数据,间断点为2015年6月。结果:政府管制政策实施后,短期内干预组药品相比于对照组的价格指数无显著变化(β_6=-0.000 452,P=0.994),但长期增长趋势显著下降(β_7=-0.050 7, P0.001)。在取消管制政策实施后,短期内干预组相较于对照组药品明显下降(β_6=-0.042 7,P=0.005);长期来看,两组药品价格指数变为上升趋势,干预组相较于对照组药品价格指数趋势变化无显著差异(β_7=0.002 83, P=0. 170)。政府管制与取消管制政策实施前后,消化类药品的用量和费用均无显著变化。结论:政府管制可以有效控制药品价格增长趋势,而取消管制在短期可以使药品价格降低,长期来看药品价格仍持续增长,价格管制或取消管制对药品的用量和费用无影响。     

Mechanism-based pharmacokinetic/pharmacodynamic modeling of the effects of sitagliptin on DPP-4 activity,insulin and glucose in diabetic rats

Dipeptidyl peptidase-4 (DPP-4) inhibitors exert their antihyperglycemic effects through repressing inactivation of certain incretin hormones and thus increasing insulin secretion and controlling glucose level. In this study, the plasma concentrations of sitagliptin, a potent DPP-4 inhibitor, after a single oral dose of 300 mg/kg in streptozotocin-induced type 2 diabetic rats were determined by HPLC. A one-compartment pharmacokinetic (PK) model with first order absorption was developed to describe the PK profile of sitagliptin, and the drug concentrations at the doses given in the pharmacodynamic (PD) study were simulated accordingly. The dynamic changes in DPP-4 activity, insulin concentration and blood glucose level in diabetic rats at doses of 1, 5 and 10 mg/kg were measured, and a mechanism-based PK/PD model was established subsequently. In this model, the inhibitory effect of sitagliptin on DPP-4 activity was demonstrated using the Hill’s function with direct link, and the downstream increase in insulin secretion and inhibition of glucose production were characterized using indirect response (IDR) models. This model interpreted the mechanism of antihyperglycemic action of sitagliptin, and may be modified and applied to other species or other agents in this class.     

Grouping schemes of welding fume exposure in shipyard welders

Welding fume exposure can increase the risk of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the optimal grouping schemes of welding fume exposure in shipyard welders for future accurate examination of the association between welding fume exposure and COPD. Industrial hygiene records, including welding fume measurements between 2002 and 2009 were collected from a shipyard. A total of 2,360 personal welding fume measurements was compiled with a geometric mean of 1.66 mg/m³ and a geometric standard deviation of 4.02. Welding jobs were categorized into 8 groups. There were 9 working areas. To obtain the optimal grouping scheme, various grouping schemes were created using job, area, and job^*area combination. To compare various grouping schemes, contrast and precision were calculated for each grouping scheme. For all measurement data, group mean ranking method created by ranking geometric means of the job^*area combination into 3 groups (group mean ranking method) showed the best contrast and precision values among various grouping schemes, followed by grouping based on the job. For a subset of the data excluding job^*area combinations with less than 10 measurements, grouping based on the job showed greater contrast than group mean ranking method, while for other subsets, including only repeated measurement data or further excluding job^*area combinations with less than 10 measurements from the repeated measurement subset, group mean ranking method showed greater contrast than grouping based on the job. Our results showed that group mean ranking or grouping based on the job could be a candidate for the optimal grouping schemes in this shipyard. Our efforts for optimal grouping scheme may aid future cohort study to elucidate the association between welding fume exposure and COPD.     

New resilience instrument for patients with cancer

Objective

Resilience is an important concept in the cancer literature and is a salient indicator of cancer survivorship. The aim of this study is to develop and validate a new resilience instrument that is specific to patients with cancer diagnosis (RS-SC) in Mainland China.

Methods

First, a resilience framework was constructed for patients with cancer diagnosis. Second, items were formulated based on the framework to reflect different aspects of resilience. Third, two rounds of expert panel discussion were performed to select important and relevant items. Finally, two cross-sectional studies were conducted to evaluate the psychometric properties of this instrument.

Results

Fifty-one items were generated based on the resilience framework and the final 25-item RS-SC resulted in a five-factor solution including Generic Elements, Benefit Finding, Support and Coping, Hope for the Future and Meaning for Existence, accounting for 64.72% of the variance. The Cronbach’s α of the RS-SC was 0.825 and the test–retest reliability was 0.874.

Conclusion

The RS-SC is a brief and specific self-report resilience instrument for Chinese patients with cancer and shows sound psychometric properties in this study. The RS-SC has potential applications in both clinical practice and research with strength-based resiliency interventions.