Verification of five pharmacogenomics-based warfarin administration models

Objective:This study aims to screen and validate five individual warfarin dosing models (four Asian model algorithms, namely, Ohno, Wen, Miao, Huang, and the algorithm of International Warfarin Pharmacogenetic Consortium, namely IWPC algorithm) with the aim of evaluating their accuracy, practicality, and safety.Results:The prediction accuracies of the Huang and Wen models were the highest. In terms of clinical practicality, the Huang model rated the highest for the low-dose group, whereas the Ohno and IWPC models rated the highest for the middle-dose group. The models tended to markedly overpredict the doses in the low-dose group, especially the IWPC model. The Miao model tended to severely underpredict the doses in the middle-dose group, whereas no model exhibited severe overprediction.Conclusions:Since none of the models ranked high for all the three criteria considered, the impact of various factors should be thoroughly considered before selecting the most appropriate model for the region''s population.KEY WORDS: Mechanical heart valve replacement, model, pharmacogenomics, verification, warfarin     

Template-Mediated Synthesis of Hierarchically Porous Metal–Organic Frameworks for Efficient CO2/N2 Separation

Carbon dioxide (CO₂) is generally unavoidable during the production of fuel gases such as hydrogen (H₂) from steam reformation and syngas composed of carbon monoxide (CO) and hydrogen (H₂). Efficient separation of CO₂ from these gases is highly important to improve the energetic utilization efficiency and prevent poisoning during specific applications. Metal–organic frameworks (MOFs), featuring ordered porous frameworks, high surface areas and tunable pore structures, are emerging porous materials utilized as solid adsorbents for efficient CO₂ capture and separation. Furthermore, the construction of hierarchical MOFs with micropores and mesopores could further promote the dynamic separation processes, accelerating the diffusion of gas flow and exposing more adsorptive pore surface. Herein, we report a simple, efficient, one-pot template-mediated strategy to fabricate a hierarchically porous CuBTC (CuBTC-Water, BTC = 1,3,5-benzenetricarboxylate) for CO₂ separation, which demonstrates abundant mesopores and the superb dynamic separation ability of CO₂/N₂. Therefore, CuBTC-Water demonstrated a CO₂ uptake of 180.529 cm³ g⁻¹ at 273 K and 1 bar, and 94.147 cm³ g⁻¹ at 298 K and 1 bar, with selectivity for CO₂/N₂ mixtures as high as 56.547 at 273 K, much higher than microporous CuBTC. This work opens up a novel avenue to facilely fabricate hierarchically porous MOFs through one-pot synthesis for efficient dynamic CO₂ separation.     

不同类型丙烯酸酯人工晶状体囊袋旋转稳定性的临床比较

目的比较不同类型丙烯酸酯折叠人工晶状体（IOL）植入后的囊袋旋转稳定性。方法将79例（83只眼）随机分为4组,A组25例（26只眼）,选择植入Aleon公司SA60AT一片式疏水性丙烯酸酯折叠IOL;B组22例（22只眼）,选择Amo公司AR40e三片式疏水性丙烯酸酯折叠IOL;C组21例（21只眼）,选择CanonStaar公司的KS—X丙烯酸酯预装式折叠IOL;D组13例（14只眼）,选择Bausch＆Lomb公司的Akreos-ADAPT一片式亲水性丙烯酸酯折叠IOL,记录术后IOL襻的位置,计算并比较IOL襻的旋转角数。结果术后3个月时旋转角度小于或者等于5°者A组为84．6％,B组为86．4％,C组为100％,D组为92．9％;术后第1周、1个月、3个月的IOL平均旋转角数A组分别为（2．04±2．32）°、（2．27±2．13）°和（2．62±2．71）°,B组分别为（2．18±2．11）°、（2．41±2．40）°和（2．73±2．57）°,C组分别为（2．00±1．95）°、（2．05±1．50）°和（2．14±1．71）°,D组分别为（1．29±2．09）°、（1．43±2．34）°和（1．50±2．31）°,各组不同时间段比较,差异无统计学意义（均P〉0．05）;四组人工晶状体的旋转度数3个月内均出现逐渐增加趋势,但平均增加不到1°。结论四种型号的丙烯酸酯折叠人工晶状体均具有良好的囊袋旋转稳定性。     

Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes

AIM: The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes. METHODS: The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)-1 and IRS-2, protein kinase B/Akt, glycogen synthase kinase-3beta(GSK-3 beta), the suppressor of cytokine signaling 3 (SOCS-3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS-3 were used to knockdown SOCS-3. RESULTS: Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin-stimulated glycogen synthesis and phosphorylation of IRS, protein kinase B/Akt, as well as GSK-3beta. Resistin treatment markedly induced the gene and protein expression of SOCS-3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS-3 treatment prevented resistin from antagonizing insulin action. CONCLUSION: The major function of resistin on liver is to induce insulin resistance. SOCS-3 induction may contribute to the resistin-mediated inhibition of insulin signaling in H4IIE hepatocytes.     

Giganteaside D induces ROS-mediated apoptosis in human hepatocellular carcinoma cells through the MAPK pathway

Purpose

Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells.

Methods and results

Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD.

Conclusions

From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.

     

When is a pathology review indicated in endometrial cancer?

OBJECTIVE: Discrepancies may exist between an original pathology report and formal pathology review, with subsequent implications for treatment. We conducted a study of pathology review in endometrial cancer from a population-based study to identify areas of discrepancy and effect on treatment. METHODS: This was a retrospective cohort study in Ontario, Canada from 1996 to 2000. We identified hysterectomy cases from patients with endometrial cancer that were subject to formal pathology review by a gynecologic pathologist at one of six tertiary care centers. Sarcomas and other rare histologic subtypes with fewer than five cases were excluded. We evaluated discrepancy between original pathology and review by demographics, stage, grade, and risk group. Four risk groups were defined: 1) low (stage I), 2) intermediate (stage I and II), 3) high-risk (stage I and II), and 4) advanced stage (all stage III and IV). Reclassification from one risk group to another upon pathology review represented a potential change in treatment. Factors associated with significant discrepancy were identified by a multivariable logistic regression model. RESULTS: Formal pathology review was available on 450 cases. There were no differences by age, year, or hospital type. The overall discrepancy rate was 42.7% (95% confidence interval 38.2-47.3%). The intermediate-risk group had the highest rate of reclassification into another group (33.1%). The most significant rates of discrepancy were associated with endometrioid grades 2 and 3 tumors and stage IIA disease (39.8%, 50.9%, and 79.6%, respectively). CONCLUSION: There was significant discrepancy between original pathology and formal review in endometrial cancer, with implications for guidelines on pathology review at a population level. LEVEL OF EVIDENCE: III     

NMDA受体依赖的神经元存活及保护作用的机制

NMDA受体属于谷氨酸受体,它在突触传递和突触可塑性中都发挥着非常重要的作用,其介导的兴奋性毒性是脑缺血、缺氧和脑外伤等导致脑损伤的重要分子机制.但是,近年来的研究发现,在生理和某些病理情况下,NMDA受体的激活具有促进神经元存活及保护神经元免受损伤的作用.     

慢性乙型肝炎患者的HDV感染

作者对69例经病理确诊为慢性乙型肝炎患者,检测了肝内δ抗原(ABC免疫组化法)和血清δ抗体(ELISA法),结果57例肝组织有 7例检出δ抗原,39例血清中 7例检出δ抗体,无 1例 δ抗原和抗体同时阳性。HDV 标志的总检出率为20.3％(14/69)。CPH和CAH之间的HDVM检出率无显著性差异。HDV感染与无HDV感染者之间,HBV复制标志无差异。HDV 感染者蛋白质代谢紊乱程度较重。发现3例肝内δ抗原和血清HB-DNA均为阳性,显示重叠HDV感染,对HBV复制未见明显抑制。     

Improvement of heat－tolerance by training I．Evaluation of effects of long－distance running and march training on heat－toleran

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