Elucidating the mechanism of nucleation inhibition of pathology crystallization of gout based on the evidence from amorphous form and in solution

The first gout attack in a hyperuricaemic patient may be regarded as a nucleation event which is caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. The effect of Tailor-Made Inhibition (TMI) may be effective as drugs for the prevention of aberrant nucleation and crystallization. Therefore, the understanding of the underlying mechanisms in inhibiting the MSUM nucleation by TMI has proven to be of great significance. Yet most of the published studies about nucleation inhibition have tended to focus on simpler molecular models with a hydrogen-bonded acceptor and donor, which may be not suitable for the uric acid molecule with multiple hydrogen-bonded acceptors and donors under physiological conditions. Herein, the mechanisms of nucleation inhibition of MSUM were explored in a simulated biological environment (0.15 M Na⁺ and pH 7.40) in the presence and absence of TMI. And the evidence of nucleation inhibition by TMI in solution and the amorphous form of MSUM was investigated by HNMR, IR, Raman, PXRD, Dynamic light scattering (DLS), induction time measurements, and density functional theory (DFT) calculations. Results showed that the inhibition comes from a combination of kinetic and thermodynamic effects, with an impact of kinetics as the TMI inhibition effects far exceeded what could be accounted for by changes in usual factors of classical nucleation theory. The data demonstrated that the complex between urate and TMI disturbed the formation of two-dimensional sheets of sodion and purine rings parallel to the (011) plane and further impeded the formation of a three-dimensional structure with aromatic stacking interactions in solution. To our knowledge, the nucleation inhibition of TMI is achieved by suppressing interplanar stacking, which is a mechanism proposed for the first time.

Xanthine, a tailor-made inhibitor, could suppress nucleation in the crystallization of gout pathology by blocking the dominant interplanar accumulation in a solution.     

Haploidentical hematopoietic stem cell transplantation may improve long-term survival for children with high-risk T-cell acute lymphoblastic leukemia in first complete remission

Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in...     

Risk of infections of biological and targeted drugs in patients with spondyloarthritis: meta-analysis of randomized clinical trials

Background: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in ...     

Leflunomide therapy for adult patients with steroid-dependent minimal change disease or primary focal segmental glomerulosclerosis

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Mixed invasive pulmonary Mucor and Aspergillus infection: a case report and literature review

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Natural killer cells in obstetric antiphospholipid syndrome

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微切口超声乳化术对糖尿病合并白内障患者眼表的影响

目的：探讨白内障超声乳化手术中2.2及3.0mm透明角膜切口对2型糖尿病患者术后泪膜功能及眼表的影响。
　　方法：收集2015-01/10在我院接受超声乳化术的2型糖尿病患者150例150眼。按照随机数字表,将其分为两组,A组微切口组(75例75眼)行2.2mm透明角膜微切口白内障超声乳化术, B 组小切口组(75例75眼)行常规3.0 mm透明角膜切口白内障超声乳化术,两组资料的人口统计学特征差异无统计学意义。观察并比较两组患者术前及术后1wk,1、3、6mo的眼表疾病指数( ocular surface disease index,OSDI)、角膜知觉、泪膜破裂时间( break-up time,BUT)和基础泪液分泌试验( Schirmer’s Ⅰtest,SⅠt)指标的变化。
　　结果：术后1wk,1、3mo,两组患者的 OSDI 评分均高于术前,且B组的OSDI评分明显高于A组,差异有统计学意义(均P<0.05);两组患者的角膜知觉均较术前降低,且B组的角膜知觉明显低于A组,差异具有统计学意义(均P<0.05);两组患者的SⅠt均低于术前,且B组的SⅠt明显低于A组,差异具有统计学意义(均 P<0.05)。术后1wk,1mo,两组患者的BUT均低于术前,且B组的BUT明显低于A组,差异具有统计学意义(均 P<0.05)。术后6mo,A组患者的OSDI、角膜知觉、BUT和SⅠt与术前相比差异不明显,无统计学意义(均P>0.05);B组患者的OSDI评分和角膜知觉与术前相比差异明显,具有统计学意义(均P<0.05);BUT和SⅠt与术前相比差异不明显,无统计学意义(均P>0.05)。
　　结论：2.2mm透明角膜微切口对眼表及泪膜的影响较小,对并发白内障的2型糖尿病患者尤为适用。     

Comparison of posterior capsule folds following intracapsular implantation of three types of intraocular lenses with different haptic design

AIM: To compare the incidence of posterior capsule folds among different types of intraocular lens (IOL) to determine risk factors of posterior capsule folds. METHODS: It was a retrospective study. We collected the cases in which the patients underwent phacoemulsification (PHACO) and IOL implantation and at least one of the three types of IOL was implanted, including 2-haptic 3-piece IOLs (HOYA PY60AD), 4-haptic 1-piece IOLs (Bausch&Lomb AO), 2-haptic 1-piece IOLs (AMO Tecnis ZCB00). The posterior capsule folds were measured using slit lamp microscope 2d after the surgery. Information of patient’s age, gender, length of ocular axis, intraocular pressure, types of IOL were recorded. Posterior capsule fold risk indicators were identified by using logistic regression analysis. RESULTS: One hundred eighty-seven patients (242 eyes) had been collected, including 80 eyes implanted with HOYA PY60AD IOLs, 81 eyes implanted with Bausch&Lomb AO IOLs, 81 eyes implanted with AMO Tecnis ZCB00 IOLs. The incidence of posterior capsule folds of patients implanted with HOYA PY60AD IOLs was significantly higher than those of patients implanted with AMO Tecnis ZCB00 IOLs. While the incidence of patients implanted with Bausch&Lomb AO IOLs was significantly lower than those of patients implanted with AMO Tecnis ZCB00 IOLs. Multi-factor logistics regression analysis demonstrated that independent risk factors were type of IOLs and length of ocular axis. Compared with AMO Tecnis ZCB00 IOLs, using HOYA PY60AD IOLs increased the risk of posterior capsule folds [P=0.020, OR (95%CI)=2.145 (1.129, 4.073)], while using Bausch&Lomb AO IOLs reduced the risk [P=0.001, OR (95%CI)=0.274 (0.127, 0.591)]. Shorter ocular axis might increase the risk of posterior capsule folds [P=0.012, OR (95%CI)=0.669 (0.489, 0.915)]. CONCLUSION: Haptic design should be an important consideration in IOL design. Compared with AMO Tecnis ZCB00 IOLs, using HOYA PY60AD IOLs is more likely to lead to posterior capsule folds formation, while using Bausch&Lomb AO IOLs is less likely to lead the formation. The posterior capsule folds are more engendered in eyes with shorter ocular axis.     

医院用药经济分析的基本方法

本文简要介绍了医院药品经济分析的基本方法，包括购药分析、处方分析、质量控制和相关文献。     

Pharmacokinetics,biodistribution and bioavailability of isoliquiritigenin after intravenous and oral administration

Context: Isoliquiritigenin (ISL) has been shown to exhibit a variety of biological activities. However, there is little research on the pharmacokinetic behavior and tissues distribution of ISL.

Objective: Pharmacokinetics, biodistribution and bioavailability of ISL after intravenous and oral administration were determined by systematic investigation in Sprague–Dawley rats.

Materials and methods: ISL was dissolved in medicinal ethanol-Tween 80–0.9% sodium chloride saline in a volume ratio of 10:15:75. The ISL solution was injected in rats via a tail vein at a single dose of 10, 20 and 50?mg/kg and administered orally in rats at a single dose of 20, 50 and 100?mg/kg, respectively. Blood samples were collected at time intervals of 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8 and 12?h after intravenous injection. Tissues of interests in mice were collected immediately at each determined time point (0.5, 1, 2, 3 and 6?h) after cervical dislocation.

Results: The dose-normalized AUC values were 7.3, 7.6 and 8.7?μg?×?h/ml (calculated based on the dose of 10?mg/kg) for intravenous doses of 10, 20 and 50?mg/kg, respectively. The elimination half-lifes (t_1/2λ) were 4.9, 4.6 and 4.8?h at 10, 20 and 50?mg/kg intravenous doses, respectively. The F values were 29.86, 22.70, 33.62% for oral doses of 20, 50 and 100?mg/kg, respectively. Liver, heart and kidney were major distribution tissues of ISL in mice. The plasma protein binding of ISL in rats was 43.72%.

Conclusion: The work may useful for further study of the bioactive mechanism of ISL.