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.     

Hepatitis D: advances and challenges

Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epid...     

Prolonged exposure to resistin inhibits glucose uptake in rat skeletal muscles

AIM: To assess the effects and mechanisms of the action of resistin on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells. METHODS: Rat myoblasts (L6) were cultured and differentiated into myotubes followed by stimulation with single commercial resistin (130 ng/mL, 0-24 h) or cultured supernatant from 293-T cells transfected with resistin-expressing vectors (130 ng/mL, 0-24 h). Liquid scintillation counting was used to quantitate [3H] 2-deoxyglucose uptake. The translocation of insulin-sensitive glucose transporters GLUT4 and GLUT1, synaptosomal-associated protein 23 (SNAP23) and GLUT protein content, as well as the tyrosine phosphorylation status and protein content of insulin receptor substrate (IRS)-1, were assessed by Western blotting. RESULTS: Treatment of L6 myotubes with single resistin or cultured supernatant containing recombinant resistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impaired insulin-stimulated GLUT4 translocation. While SNAP23 protein content was decreased, no effects were noted in GLUT4 or GLUT1 protein content. Resistin also diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels without affecting its protein content. The effects of recombinant resistin from 293-T cells transfected with resistin-expressing vectors were greater than that of single resistin treatment. CONCLUSION: Resistin regulated IRS-1 function and decreased GLUT4 translocation and glucose uptake in response to insulin. The downregulated expression of SNAP23 may have been partly attributed to the decrease of glucose uptake by resistin treatment. These observations highlight the potential role of resistin in the pathophysiology of type 2 diabetes related to obesity.     

B超检查高血压患者颈动脉粥样硬化斑块的研究

目的 探讨B超检查高血压患者颈动脉粥样硬化斑块对高血压的诊断价值。方法 应用高频彩超检测原发性高血压患者194例。结果 颈动脉粥样梗化斑块检出37例，检出率为35．7％。高血压患者年龄越大，病史越长，检出率越高。结论 颈动脉粥样硬化斑块是高血压靶器官损害的标志之一，高血压是颈动脉结构及功能改变的主要因素之一，B超检查颈动脉粥样硬化斑块对临床判断高血压病情有一定的价值。     

甲基莲心碱通过p62抑制肺腺癌A549细胞侵袭、转移的机制

目的 阐明甲基莲心碱（Nef）抑制肺腺癌A549细胞侵袭和转移的可能机制,为今后临床应用Nef防治肺腺癌转移提供理论基础。方法 常规培养肺腺癌A549细胞,加入不同浓度的Nef进行干预,CCK-8检测细胞活力;将A549细胞分为三组：空白组不做任何处理,TGF-β组采用TGF-β1干预,TGF-β+Nef组采用TGF-β1和Nef干预,显微镜下观察细胞形态;Transwell和Wound healing法检测各组细胞的侵袭和迁移能力; PCR、Western blotting检测各组细胞上皮间质转化（EMT）相关基因和蛋白的表达,电镜下验证细胞自噬,p62基因沉默进一步明确作用机制。结果 Nef可明显抑制TGF-β1诱导的A549细胞EMT,并可能通过抑制Twist1自噬降解抑制A549细胞的侵袭和迁移。结论 Nef可抑制肺腺癌A549细胞的侵袭和转移,其机制可能与促进p62介导的Twist1选择性自噬降解有关。     

微创椎间盘切除术治疗老年腰椎间盘突出症34例

目的探讨微创椎间盘切除术治疗老年腰椎间盘突出症的效果。方法选择2010年1月—2014年1月南充市中心医院收治的符合微创椎间盘切除术适应证的老年腰椎间盘突出症34例,行经Quadrant通道微创椎间盘切除术。记录手术时间、术中失血量、手术至开始行走时间、住院时间、住院费用;分别于术后第1、2、3、6个月随访1次,之后每半年随访1次。术前、术后2周及末次随访时行疼痛视觉模拟（VAS）评分评估腰腿痛的程度。末次随访时使用Macnab标准判定疗效。结果本组手术时间平均75 min,术中失血量平均150 ml,住院时间平均13 d,住院费用平均7430元,手术至开始行走时间平均11 d。随访时间5-53个月,平均18个月。术后2周及末次随访时VAS评分均低于术前（t=4.353、7.865,P〈0.05）,末次随访时VAS评分低于术后2周（t=6.597,P〈0.05）。末次随访时疗效：优20例,良8例,可5例,差1例,优良率82.35%。结论微创椎间盘切除术治疗老年腰椎间盘突出症有良好的效果。     

盐酸米托蒽醌有关物质测定的3种标准方法比较

目的比较研究测定盐酸米托蒽醌有关物质的3种标准测定方法。方法这3种方法分别收载于美国药典（USP24-32）、中国药典（2000,2005年版二部）和国家药品标准犤WS1-（X-038）-2002Z和WS1-（X-040）-2002Z犦中。美国药典和国家药品标准方法采用高效液相色谱法,色谱柱分别为μBondapak^TMPhenyl（300mm×3.9mm,10μm,125A）和PromosilC18（250mm×4.6mm,5μm,100A）,流动相为水-乙腈-庚烷磺酸钠溶液。结果国家药品标准中的高效液相色谱（HPLC）法测定盐酸米托蒽醌有关物质优于美国药典和中国药典方法。结论建议测定盐酸米托蒽醌有关物质时推广使用国家药品标准中的高效液相色谱法。     

表阿霉素联合XELOX方案治疗晚期胃癌疗效与安全性分析

目的探讨表阿霉素联合XELOX(奥沙利铂联合希罗达)治疗晚期胃癌的疗效及安全性。方法收集我院2006年6月～2010年12月采用表阿霉素联合XELOX方案(即EOX方案)治疗的晚期胃癌进行回顾性分析,并与奥沙利铂联合希罗达化疗方案(单纯XELOX方案)进行比较。EOX组54例,XELOX组66例。结果 EOX方案组总有效率为38.9%(21/54),XELOX方案组总有效率36.4%(24/66),两组间无显著性差异(P>0.05);XELOX方案组手足综合征的发病率较EOX方案组高,但大多都为Ⅰ～Ⅱ度反应,而Ⅲ～Ⅳ度骨髓抑制、消化道反应、脱发的发病率较EOX低,两组差异有统计学意义(P<0.05)。结论表阿霉素联合XELOX方案治疗晚期胃癌的疗效与单纯XELOX方案治疗的疗效相近,毒副作用可耐受,对于体质较弱或对多次化疗反应后耐受性较差的患者,可能更适合单纯XELOX化疗方案。