山东省人群血清尿酸变异性与冠心病发病风险的关系

目的 探讨山东省人群队列中血清尿酸变异性指标和冠心病发病风险之间的关系。 方法 依托山东省健康医疗大数据平台,构建30岁到80岁人群的冠心病发病队列。采用Cox比例风险模型研究不同血清尿酸变异性指标与冠心病发病风险的关系。变异性指标包括独立于均值的变异(VIM)、平均真实变异(ARV)和变异系数(CV)。 结果 在中位随访时间为8.50年的观察期间,新发冠心病患者1 931例,其中男1 420例,女511例,发病密度为10.60/千人年。在调整了年龄、性别、收缩压、空腹血糖、体质量指数、甘油三酯、高密度脂蛋白、低密度脂蛋白、平均血清尿酸水平和随访次数后,与血清尿酸变异性(VIM)的最低四分位组相比,第二到第四四分位组的HR分别为1.03(95%CI:0.90~1.19,P=0.674)、1.18(95%CI:1.03~1.35,P=0.018)和1.32(95%CI:1.16~1.51,P<0.001)。用ARV和CV表示变异所得到的结果与VIM类似。 结论 高水平的血清尿酸变异性是冠心病发病的风险因素。     

Prospective Evaluation of a Peritoneal Dialysis Catheter System for Large Volume Paracentesis

Large volume paracentesis is becoming a popular form of therapy for patients with massive ascites and cirrhosis. Although the physiologic effects of the removal of large amounts of ascitic fluid have been well described, the techniques utilized to perform the procedure are either not well documented or not currently available. Over a 13-month period, 52 patients with moderate to severe ascites have undergone 73 large volume paracenteses with a peritoneal dialysis catheter system. The mean volume of ascitic fluid removed was 7.6 L, with a mean time of removal of 129 min. Total paracentesis was accomplished within 1 h in 38% of procedures. The most common site for paracentesis was the left lower quadrant. Complications related to the procedure were few, the most common being a self-limited ascitic fluid leak at the sight of paracentesis. No patient experienced intestinal perforation, peritonitis, or a significant change in serum creatinine after the procedure. The widely available peritoneal dialysis catheter system represents a safe and rapid technique for the removal of large quantities of ascitic fluid.     

Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity

Recent studies suggest that HIV-1 budding occurs selectively from detergent-insoluble membrane domains, referred to as lipid rafts. Palmitoylation is thought to be one of the factors responsible for targeting membrane proteins to lipid rafts. The cytoplasmic domain of the HIV-1 envelope glycoprotein (gp160) contains two palmitoylated cysteine residues. In this work, we studied the solubility of gp160 after detergent extraction. We show that wild-type gp160 is mostly insoluble after ice-cold Triton X-100 extraction, but that it becomes almost completely soluble at 37 degrees C. In contrast, we find that a mutant gp160, in which the two palmitoylated cysteine residues are replaced by serine, is Triton X-100 soluble even under ice-cold extraction. These findings are consistent with the properties of proteins that localize to lipid rafts and strongly suggest that gp160 is associated with lipid rafts. Further, removal of both palmitoylation sites results in the formation of virus with low levels of gp160 incorporation as well as a decrease in viral infectivity by 60-fold. Our results strongly support the suggestion that HIV-1 buds from lipid rafts and point to a role for rafts as a viral assembly hub.     

环氧化酶-2及细胞色素芳香化酶基因mRNA在育龄妇女子宫内膜息肉中的表达

目的研究环氧化酶-2(COX-2)基因和细胞色素芳香化酶P450(P450 arom)基因在育龄妇女子宫内膜息肉(EP)中的表达及相关性。方法应用逆转录聚合酶链反应(RT-PCR)技术,检测15例正常子宫内膜、30例育龄妇女EP及息肉周围内膜中COX-2 mRNA和P450arom mRNA的表达,并进行相关性分析。结果COX-2mRNA和P450arom mRNA在EP及息肉周围内膜中均有较强表达。EP中COX-2和P450 arom的表达与息肉周围内膜相比均无显著性差异(P均>0.05)。在EP中,P450 arom和COX-2 mRNA表达与月经周期无关(P均>0.05)。在息肉周围内膜中,P450 arom mRNA和COX-2 mR-NA在分泌期的表达均明显高于增生期(P均<0.01)。P450 arom在EP及息肉周围内膜中的表达与COX-2呈正相关。结论COX-2和P450 arom与育龄妇女EP的发病相关,二者协同作用促进EP的发生与发展。     

微乳法制备丹皮酚纳米结构脂质载体

目的以丹皮酚为模型药物,微乳法制备纳米结构脂质载体（NLC）。方法采用伪三元相图法对构建纳米脂质载体的初乳液进行筛选,经体外透皮试验确定处方。结果硬脂酸为固态脂质（占初乳处方的1％）,油酸乙酯为液态脂质（占初乳处方的1％）,LabrasoL为乳化剂,TranscutoLP为助乳化剂,Km：2：1,含水量50％,采用注射器滴入法分散于0℃冷水中,可以快速制得载药量10％的丹皮酚纳米脂质载体。结论微乳法制备的丹皮酚纳米脂质载体制备．f-艺简单、操作方便,不需使用有机溶剂（如二氯甲烷、氯仿等）和复杂设备,适合纳米结构脂质载体的研究和小规模制备。     

卵巢交界性肿瘤的临床特征及危险因素分析

目的 分析卵巢交界性肿瘤(BOTs)的危险因素和临床特征。方法 选取275例经手术病理确诊BOTs患者作为研究对象,另随机选取275例经手术病理确诊卵巢良性上皮性肿瘤(BETs)患者进行病例对照研究。收集并比较患者的年龄、生育情况、症状体征、超声影像学检查结果、血清肿瘤标志物水平、手术记录及病理结果等临床资料,分析BOTs的危险因素。根据术后病理类型将部分BOTs患者分为卵巢交界性黏液性肿瘤(MBOTs)组和卵巢交界性浆液性肿瘤(SBOTs)组,比较2组患者的临床特征。结果 超声显示成分以实性为主、囊壁有乳头、有血流信号、糖类抗原125(CA125)及糖类抗原199(CA199)升高均为BOTs的独立危险因素(P<0.05); BOTs与BETs在肿瘤最大径、肿瘤位置、是否多房和血清癌胚抗原水平方面比较,差异无统计学意义(P>0.05)。MBOTs组超声显示肿瘤最大径≥10 cm、多房、有血流信号和CA199升高者占比均高于SBOTs组,超声显示肿瘤位于双侧、有乳头和CA125升高者占比均低于SBOTs组,差异有统计学意义(P<0.05)。结论 BOTs患者超声检查显...     

宫颈环形切除术在宫颈上皮内瘤变诊治中的价值

目的 探讨宫颈环形切除术(LEEP)诊治宫颈上皮内瘤变(CIN)的价值.方法 回顾性分析LEEP患者561例资料.结果 LEEP和阴道镜下多点活检的病理结果 完全符合348例(62.0%),升级121例(21.6%);CIN患者LEEP一次性治愈503例(94.0%),LEEP术后再行子宫切除术68例,术后病灶残存33例;LEEP术前高危型人乳头瘤病毒(HR-HPV)负荷量(≥300RLU/PC)对病灶残存的预测有统计学意义(P＜0.05).结论 LEEP是诊治CIN的有效手段;LEEP术前HR-HPV负荷量高低对预测术后病灶残存有临床意义.     

认清形势抓契机,精心策划谋发展

新的一年是我国实行改革开放的30周年,是举世瞩目的奥运年,是党的十七大以后的第一年.目前,尽管还有这样那样的矛盾和困难,但这是前进中、发展中的问题,还得靠发展去克服、解决.     

片剂创新设计与质量控制新技术应用进展

片剂一直是临床应用中的重要制剂,但传统片剂的开发设计模式、质量评价技术及生产质量控制模式难以满足现在的需求。本文综述了多变量数据分析技术、人工神经网络技术、3D打印技术在片剂设计开发的应用,实现了片剂的快速制备和个性化生产;论述了近红外光学技术、太赫兹脉冲成像技术、核磁共振成像技术等新型检测技术在片剂质量评价的应用,相比传统的检测技术,新的检测技术呈现出高效、灵敏、便捷等特点,同时在建立片剂开发与生产的质量控制策略中遵循质量源于设计的理念,对提升片剂安全性和有效性以及片剂的开发和生产具有重要意义。     

Association of KMT2C/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer

Immune checkpoint inhibitors (ICIs) have become important treatment strategies, yet responses vary among patients and predictive biomarkers are urgently needed. Mutations in KMT2C and KMT2D lead to increased levels of genomic instability. Therefore, we aimed to examine whether KMT2C/D mutations might be a predictor of immunotherapeutic efficacy. Here, we investigated the associations of KMT2C/D loss-of-function (LOF) variants with tumor mutation burden (TMB), MSI-H, PD-L1 expression, the levels of tumor-infiltrating leukocytes (TILs), and clinical response to ICIs. It was found that KMT2C/D LOF variants were associated with higher TMB. Compared with the non-LOF group, the proportion of patients with MSI-H tumors was larger in the LOF group. PD-L1 expression was higher in the LOF group only for colorectal cancer in both the Chinese and The Cancer Genome Atlas cohorts. Importantly, KMT2C/D LOF variants were associated with decreased regulatory T cells and increased levels of CD8⁺ T cells, activated NK cells, M1 macrophages, and M2 macrophages in colorectal cancer. However, there was no significant association between KMT2C/D LOF and TILs levels in other cancer types. Consistently, the results showed that KMT2C/D LOF variants were associated with prolonged overall survival only in colorectal cancer (p = 0.0485). We also presented that patients with KMT2C/D LOF mutations exhibited a better clinical response to anti-PD-1 therapy in a Chinese colorectal cancer cohort (p = 0.002). Taken together, these results suggested that KMT2C/D LOF variants could be a useful predictor for ICIs efficacy in colorectal cancer. In addition, the predictive value of KMT2C/D LOF variants was consistent with their association with TILs levels.