胆汁酸-肠道菌群轴在2型糖尿病中的作用

目的 分析2型糖尿病(type 2 diabetes mellitus,T2DM)患者和正常人群胆汁酸与肠道菌群差异,探讨胆汁酸-肠道菌群轴在T2DM中的作用。方法 利用代谢组学、16S rRNA测序手段分别对T2DM患者中的血清胆汁酸含量及粪便肠道微生物进行检测及分析,结合斯皮尔曼相关性分析,明确胆汁酸-肠道菌群在T2DM中的代谢对话关系。结果 血清胆汁酸含量和肠道微生物的丰度在T2DM患者与正常人群中存在一定的差异。与正常人群相比,甘氨熊脱氧胆酸、牛磺鹅脱氧胆酸、甘氨鹅脱氧胆酸的含量在T2DM患者中显著降低;T2DM患者中肺炎克雷伯菌属、普拉梭菌属的相对丰度较正常人群明显升高,而狄氏副拟杆菌属、普雷沃菌属、艾克曼菌属、双歧杆菌属的相对丰度明显降低;斯皮尔曼相关性分析表明甘氨熊脱氧胆酸与狄氏副拟杆菌属、艾克曼菌属呈正相关,与克雷伯氏菌属呈负相关。结论 胆汁酸-肠道菌群轴是维持机体稳态的必要因素,在T2DM中发挥重要作用。     

熊果酸前药的设计合成及抗多发性硬化症活性评价

目的 设计、合成熊果酸前药,以改善熊果酸的水溶性,并对其抗多发性硬化症(multiple sclerosis,MS)活性进行评价。方法 根据前药策略,选取了琥珀酸、二肽氨基酸和艾莎康唑侧链片段,通过缩合、酯化反应等与熊果酸的3位羟基进行结合,采用紫外-可见分光光度法测定前药的水溶性,并建立小鼠实验性自身免疫性脑脊髓炎模型来进行抗MS活性评价。结果 共合成了3个前药,目标化合物的结构经¹H-NMR、¹³C-NMR和LCMS(ESI)进行确证;前药1和2水溶性较熊果酸提升110倍以上,前药3水溶性提升200倍以上;体内抗MS活性结果显示,所得前药化合物的抗MS活性均有一定提高,其中前药1的抗MS活性显著高于熊果酸组,其机制可能是通过抑制外周炎症细胞浸润中枢以及抗脱髓鞘从而发挥抗MS活性;前药1体内代谢结果显示,前药1以原型形式在体内的暴露量为熊果酸的6倍,表明前药1可能主要是以钠盐原型发挥抗MS活性。结论 前药1具有较大的抗MS潜力,值得深入研究。该研究为开发具有抗MS活性的熊果酸前药提供一定依据及有益指导。     

院前使用血凝酶或氨甲环酸对颅脑损伤患者止血效果及预后影响的研究

目的： 探讨院前使用血凝酶或氨甲环酸对颅脑损伤患者止血效果及预后的影响。方法： 选择2016年1月至2019年6月期间本院神经外科住院部收治的颅脑损伤患者124例,采用随机数字表法将患者分为血凝酶组和氨甲环酸组,各62例。血凝酶组院前使用血凝酶进行止血治疗;氨甲环酸组院前使用氨甲环酸进行止血治疗。结果： 血凝酶组平均出血量明显少于氨甲环酸组,治疗前,两组Hb水平比较差异无统计学意义（P>0.05）,治疗后,两组Hb水平较治疗前明显降低,P<0.05;血凝酶组Hb水平较氨甲环酸组明显增高,P<0.05。治疗前,两组HCT、Fib、APTT、PT、PAR水平比较差异无统计学意义（P>0.05）,治疗后,两组HCT、PAR水平较治疗前明显降低,P<0.05,而两组治疗前后Fib、APTT、PT水平比较差异无统计学意义（P>0.05）。治疗后,血凝酶组HCT、PAR水平较氨甲环酸组明显增高,P<0.05,两组Fib、APTT、PT水平比较差异无统计学意义（P>0.05）。血凝酶组再出血率、预后不良率为1.61%、22.58%,明显低于氨甲环酸的11.29%、40.32%,P<0.05。两组药物不良反应发生率比较差异无统计学意义（P>0.05）。结论： 与院前使用氨甲环酸比较,血凝酶对颅脑损伤患者止血效果更满意,有利于更明显降低再出血风险,改善预后状况,且不增加血栓性疾病的发生风险,值得临床推广应用。     

吡格列酮联合二甲双胍对2型糖尿病周围神经病变患者血尿酸变化的影响

目的 探讨吡格列酮对2型糖尿病周围神经病变患者血尿酸变化的影响。方法 收集2014年7月-2015年7月在南通市通州区第三人民医院住院并确诊患有糖尿病周围神经病变的患者80例,随机分为对照组和观察组各40例,两组患者均进行饮食控制结合运动疗法等一般治疗方式。对照组给予二甲双胍治疗,0.5 g/次,每日3次。观察组在对照组的基础上给予吡格列酮治疗,吡格列酮剂量为15 mg/次,每日1次。两组服药时间均为2个月。结果 两组空腹血糖及餐后2 h血糖浓度经治疗后均降低,观察组低于对照组（P<0.05）;对照组治疗前后血尿酸差异无明显变化（P>0.05）,观察组治疗后血尿酸浓度显著降低（P<0.05）;两组治疗后CSS评分均低于治疗前评分（P<0.05）;治疗后观察组评分低于对照组（P<0.05）。结论 吡格列酮联合二甲双胍对治疗2型糖尿病周围神经病变有一定疗效,可降低2型糖尿病周围神经病变患者血尿酸水平。     

Comparison of the effect of a hyaluronate–trehalose solution to hyaluronate alone on Ocular Surface Disease Index in patients with moderate to severe dry eye disease

Objective: To describe a post hoc analysis comparing the effect of a hyaluronic acid (HA)–trehalose solution to an established eyedrop solution containing HA alone using Ocular Surface Disease Index (OSDI) score <19 as a threshold for moderate to severe dry eye disease (DED).

Methods: A phase III, randomized, controlled, single-blind, multicenter study was conducted in France and Tunisia to evaluate the efficacy and safety of HA–trehalose (N?=?52) and HA (N?=?53) administered for 84 days. Eligible patients had moderate to severe DED with OSDI ≥18. Here the results of a post hoc analysis of the percentage of patients with OSDI <19 on Day 35 and Day 84 are reported.

Results: Significantly more patients had OSDI <19 at Day 84 in the HA–trehalose group than in the HA group (78.8% versus 58.5%; p?=?.025). At Day 35, more patients had OSDI <19 in the HA–trehalose group than in the HA group, but this difference was not statistically significant. Furthermore, approximately twice as many patients in the HA group (41.5%) still had OSDI 19–100 at Day 84 compared to the HA–trehalose group (21.2%).

Conclusions: This data supports the addition of trehalose to HA-containing eyedrop solutions to provide better symptomatic relief from moderate to severe DED, based on an OSDI score of <19 after 84 days of treatment.     

原发性高血压患者血浆纤维蛋白原含量与血压水平的相关性分析

目的 探讨血浆纤维蛋白原水平与原发性高血压患者血压水平的关系,明确原发性高血压患者血压显著升高的危险因素及其相关性。方法 选取2012年9月至2014年12月郑州大学第一附属医院收治的258例原发性高血压患者,按血压控制水平分为正常血压组（68例）、1级高血压组（63例）、2级高血压组（79例）、3级高血压组（48例）。采用Kruskal-Wallis检验及Mann-Whitney U检验比较4组纤维蛋白原血浆水平。采用logistic回归分析筛选促使血压显著升高的影响因素。利用Spearman相关分析纤维蛋白原与这些影响因素的相关性。结果 3级高血压组的血浆纤维蛋白原水平与其他3组比较,差异有统计学意义（P<0.01）,而其他3组间纤维蛋白原水平的差异无统计学意义（P>0.05）。logistic回归分析显示,血糖升高（OR=2.746,P=0.004）、胆固醇升高（OR=2.169,P=0.037）、肌酐升高（OR=2.711,P=0.011）以及尿酸升高（OR=2.975,P=0.002）是3级高血压形成的重要危险因素。Spearman相关分析结果显示纤维蛋白原与血糖、胆固醇及尿酸无相关性（P>0.05）,仅与血肌酐呈弱相关（r=0.173,P=0.005）。结论 纤维蛋白原水平升高是血压升高的促进因素。血糖、胆固醇、肌酐及尿酸水平的升高对于极高危高血压（3级高血压）的形成有促进作用。     

2018—2019年西安交通大学第二附属医院鲍曼不动杆菌的分布及耐药性分析

目的 分析西安交通大学第二附属医院鲍曼不动杆菌的临床分布及耐药性,为临床医师选择合理的抗感染治疗方案提供参考依据。方法 以2018年1月-2019年12月西安交通大学第二附属医院住院的患者为研究对象,按照美国临床实验室标准化委员会（CLSI）推荐的方法进行鲍曼不动杆菌的初步筛选,用梅里埃VITEK 2 Compact全自动细菌鉴定及药敏分析系统进行细菌鉴定和药敏实验,用Excel进行数据统计分析。结果 2018-2019年本院住院患者中共分离出935株鲍曼不动杆菌,主要分布于急诊科,共181株;主要来源于痰液标本,共676株。感染人群主要为14岁以上的中青年及老年患者。药敏结果显示鲍曼不动杆菌对替卡西林/克拉维酸、多西环素、哌拉西林/他唑巴坦具有较高的耐药性,耐药率依次为87.43%、75.96%、64.98%;鲍曼不动杆菌对黏菌素、阿米卡星和替加环素具有良好的敏感性,敏感率依次为99.61%、85.02%、73.56%。结论 本院临床上鲍曼不动杆菌感染的高发人群为14岁以上的中青年及老年患者,鲍曼不动杆菌对多种抗生素都有很强的耐药性,应加强病原菌培养及耐药性监测,指导临床医师合理使用抗生素。     

Preclinical and clinical activity of the topoisomerase I inhibitor,karenitecin, in melanoma

Introduction: This review covers the preclinical and clinical activity of the novel camptothecin analog, karenitecin, in melanoma.

Areas covered: While the camptothecins are widely used antitumor agents that inhibit topoisomerase I, their utility is limited by instability, high interpatient variability and the development of drug resistance. Karenitecin was rationally designed to overcome these limitations. The authors review the data on karenitecin in preclinical models and in clinical trials in melanoma using studies published in Medline and reports presented at AACR and ASCO.

Expert opinion: Karenitecin shows activity in melanoma, both as a single agent and in combination. In adverse prognostic factor melanoma, karenitecin showed prolonged disease stabilization in 34% of patients. Because preclinical studies suggested a synergistic interaction between karenitecin and HDAC inhibitors, a schedule-specific combination Phase I–II trial of valproic acid and karenitecin was carried out in heavily pretreated melanoma patients which showed a benefit rate in 47% patients with acceptable toxicity. The treatment for melanoma is in rapid transition and genomic profiling is now an integral part, and hence the optimal use of karenitecin in melanoma should be re-evaluated with regard to specific mutational status.     

A new p-hydroxybenzoic acid derivative from an endophytic fungus Penicillium sp. of Nerium indicum

A new p-hydroxybenzoic acid derivative named 4-(2′R, 4′-dihydroxybutoxy) benzoic acid (1) was isolated from the fermentation of Penicillium sp. R22 in Nerium indicum. The structure was elucidated by means of spectroscopic (HR-ESI-MS, NMR, IR, UV) and X-ray crystallographic methods. The antibacterial and antifungal activity of compound 1 was tested, and the results showed that compound 1 revealed potent antifungal activity against Colletotrichum gloeosporioides, Alternaria alternata, and Alteranria brassicae with MIC value of 31.2 μg/ml.     

Cameroonemide A: a new ceramide from Helichrysum cameroonense

From the extracts of all parts of the plant Helichrysum cameroonense, five compounds were isolated and identified. One of them, a ceramide, named cameroonemide A (1), is reported for the first time as a new natural product. Its structure was determined by comprehensive analyses of their 1D and 2D NMR and HR-EI-MS spectral data. The remaining four known compounds were identified by comparing their spectroscopic data with those reported in the literature as kaurenoic acid (2), 3-acetyloxykaurenoic acid (3), β-sitosterol (4), and β-sitosterol glucopyranoside (5). Preliminary studies showed that 3-acetyloxykaurenoic acid (3) inhibited the alga Chlorella fusca, while kaurenoic acid (2) showed strong antibacterial activity against Bacillus megaterium.     

Uric acid: role in cardiovascular disease and effects of losartan

SUMMARY

A substantial body of epidemiological and experimental evidence suggests that serum uric acid is an important, independent risk factor for cardiovascular and renal disease especially in patients with hypertension, heart failure, or diabetes. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Further, patients with hypertension and hyperuricemia have a 3- to 5-fold increased risk of experiencing coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels. Although the mechanisms by which uric acid may play a pathogenetic role in cardiovascular disease is unclear, hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemorheology, and aggregation. Xanthine oxidase inhibitors (e.g., allopurinol) or a

variety of uricosuric agents (e.g., probenecid, sulfinpyrazone, benzbromarone, and benziodarone) can lower elevated uric acid levels but it is unknown whether these agents reversibly impact cardiovascular outcomes. However, the findings of the recent LIFE study in patients with hypertension and left ventricular hypertrophy suggest the possibility that a treatment-induced decrease in serum uric acid may indeed attenuate cardiovascular risk. LIFE showed that approximately 29% (14% to 107%, p?=?0.004) of the treatment benefit of a losartan-based versus atenolol-based therapy on the primary composite endpoint (death, myocardial infarction, or stroke) may be ascribed to differences in achieved serum uric acid levels. Overall, serum uric acid may be a powerful tool to help stratify risk for cardiovascular disease. At the very least, it should be carefully considered when evaluating overall cardiovascular risk.     

Emerging drugs for the treatment of Primary Biliary Cholangitis

Introduction: Primary biliary cholangitis (PBC) is an autoimmune chronic disease of the liver that can progress to cirrhosis and hepatocellular carcinoma. It affects approximately 1 in 4,000 with a 10:1 female to male ratio. The diagnosis of PBC can be made based on serum antimitochondrial antibodies (AMA) in a patient with abnormally high serum alkaline phosphatase after ruling out other causes of cholestasis and biliary obstruction. Genome-wide association studies have revealed several human leukocyte antigen (HLA) and non-HLA risk loci in PBC, and complex environmental-host immunogenetic interactions are believed to underlie the etiopathogenesis of the disease. Fatigue and pruritus are the most common and often problematic symptoms; although often mild, these can be severe and life-alternating in a subset of patients. Ursodeoxycholic acid (UDCA) is the only drug approved by the United States Food and Drug Administration for the treatment of PBC. Clinical trials have shown that UDCA significantly improves transplant-free survival. However, nearly 40% of PBC patients do not respond adequately to PBC and are at higher risk for serious complications when compared to PBC patients with complete response to UDCA.

Areas Covered: Here we provide a detailed discussion regarding novel therapeutic agents and potential areas for further investigation in PBC-related research.

Expert Opinion: Results of ongoing clinical trials and emerging treatment paradigms for PBC will likely further improve medical management of this disorder in the near future.     

Patent Evaluation: Molecular detection and identification of a new mycobacterium

Summary

Novelty: A new mycobacterial species M. genavense sp. is claimed together with a nucleic acid probe capable of hybridising to the nucleotide sequence of the mycobacterium and a method of detecting M. genavense in a sample. This mycobacterium is stated to occur as an opportunistic infection in AIDS patients.

Biology: The new mycobacterium was detected and characterised from samples from two AIDS patients. Subsequently, sixteen other AIDS patients were found to be similarly infected with this organism.

Chemistry: Full details for the amplification and sequencing of the 16S and RNA gene of M. genavense are given together with details for using the resulting nucleic acid probe for detecting M. genavense infection.     

非布司他治疗慢性肾病伴高尿酸血症的疗效和机制分析

目的 分析非布司他治疗慢性肾病伴高尿酸血症的疗效和机制。方法 回顾2015年10月-2017年10月到河南医学高等专科学校附属医院诊治的慢性肾病伴高尿酸血症的患者共108例,按照随机原则分为两组,观察组54例患者采用非布司他治疗,对照组54例患者采用别嘌醇治疗,疗程均为24周。检测两组患者治疗前后血尿酸（UA）、血肌酐（Scr）、肾小球滤过率估算值（eGFR）、血尿素氮（BUN）、血白蛋白（Alb）和尿微量蛋白尿（u-mAlb）水平,比较两组患者疗效,记录肝功能受损、皮疹、胃肠道反应和血脂升高等不良反应发生情况。结果 治疗前两组患者各项指标无明显差异;治疗后UA、Scr、BUN、u-mAlb、eGFR均较治疗前明显降低,Alb较治疗前明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且治疗后观察组患者UA、Scr、BUN和u-mAlb明显低于对照组,eGFR和Alb明显高于对照组,差异均有统计学意义（P<0.05）。观察组患者高尿酸血症治疗总有效率为77.78%,明显高于对照组患者的55.56%,差异有统计学意义（P<0.05）;观察组患者肾功能治疗总有效率为83.33%,明显高于对照组患者的62.96%,差异有统计学意义（P<0.05）。观察组肝功能受损、皮疹、胃肠道反应和血脂升高等不良反应发生率明显低于对照组,差异有统计学意义（P<0.05）。结论 非布司他治疗慢性肾病伴高尿酸血症疗效确切,能够有效降低血尿酸水平,保护患者肾功能,不良反应发生率低,建议临床推广应用。     

The Fate of Plasmid DNA After Intravenous Injection in Mice: Involvement of Scavenger Receptors in Its Hepatic Uptake

Purpose. We examined the stability and disposition characteristics of a naked plasmid DNA pCAT as a model gene after intravenous injection in mice to construct the strategy of in vivo gene delivery systems. Methods. After the injection of pCAT to the mice, stability, tissue distribution, hepatic cellular localization, and effect of some polyanions on the hepatic uptake were studied. Results. The in vitro study demonstrated that the pCAT was rapidly degraded in mouse whole blood with a half-life of approximately 10 min at a concentration of 100 µg/ml. After intravenous injection, pCAT was degraded at a significantly faster rate than that observed in the whole blood, suggesting that pCAT in vivo was also degraded in other compartments. Following intravenous injection of [³²P] pCAT, radioactivity was rapidly eliminated from the plasma due to extensive uptake by the liver. Hepatic accumulation occurred preferentially in the non-parenchymal cells. The hepatic uptake of radioactivity derived from [³²P] pCAT was inhibited by preceding administration of polyanions such as polyinosinic acid, dextran sulfate, maleylated and succinylated bovine serum albumin but not by polycytidylic acid. These findings indicate that pCAT is taken up by the liver via scavenger receptors on the non-parenchymal cells. Pharmacokinetic analysis revealed that the apparent hepatic uptake clearance was fairly close to the liver plasma flow. Conclusions. These findings provide useful information for the development of delivery systems for in vivo gene therapy.     

肾移植术后高尿酸血症应用非布司他和别嘌醇的有效性与安全性

目的对应用不同降尿酸药物的肾移植术后高尿酸血症患者分析,比较非布司他与别嘌醇治疗肾移植术后高尿酸血症的有效性与安全性。方法回顾肾移植术后高尿酸血症患者的降尿酸治疗方案,按使用的降尿酸药物不同,分成两组,非布司他组和别嘌醇组,分别分析患者的尿酸控制水平,对比分析两组的区别。结果非布司他组尿酸水平远低于别嘌醇组,成组t检验P<0.05,两组差异具有统计学意义。结论肾移植术后高尿酸血症患者,应用非布司他组的尿酸水平控制优于别嘌醇组。同时根据大量文献数据,在应用非布司他或其他降尿酸药物应密切监测患者相关指标及不良反应,尤其对于肾移植术后患者。     

A double-blind trial of methocarbamol versus placebo in painful muscle spasm

Summary

A double-blind trial of methocarbamol versus placebo was carried out in 59 matched pairs of patients suffering from painful muscle spasm. Methocarbamol {1500?mg. q.d.s) was found to be effective in approximately 60 % of patients compared with 30 % of patients receiving placebo (p< 0.01). Side-effects were of almost equal incidence in the two groups.     

丁苯酞对老年急性脑梗死的疗效及对血清尿酸、C反应蛋白和血液流变学的影响

目的 研究丁苯酞对老年急性脑梗死的疗效及对血清尿酸、C反应蛋白和血液流变学的影响。方法 选择2015年1月-2015年12月在西安市第一医院进行诊治的老年急性脑梗死患者86例，随机分为两组，对照组采用常规急性脑梗死对症治疗，观察组加用丁苯酞胶囊。观察两组的美国国立卫生研究院卒中量表（NIHSS）评分、Barthel指数和疗效，检测并比较治疗前后两组患者血清尿酸、C反应蛋白、血小板聚集率和血黏稠度。结果 观察组的有效率为90.70%，明显高于对照组的72.09%（P<0.05）；治疗后两组的NIHSS评分、血清尿酸和C反应蛋白水平、血小板聚集率和血黏稠度均明显降低，Barthel指数明显升高（P<0.05），且观察组的变化较对照组更为明显（P<0.05）。结论 丁苯酞对老年急性脑梗死患者的疗效显著，能降低患者的血清尿酸、C反应蛋白水平和神经功能缺损程度，改善其血液流变学状态和生活自理活动能力，具有脑保护作用。     

氨甲环酸静脉滴注联合关节腔注射对初次全膝关节置换患者术后出血量的影响

目的 探讨氨甲环酸静脉滴注联合关节腔注射对初次行全膝关节置换患者术后出血量的影响。方法 以2015年1月至2015年5月收治的45例重度膝骨关节炎行初次全膝关节置换的患者为研究对象,随机分为氨甲环酸组(23例)与对照组(22例)。氨甲环酸组术中松止血带前30 min静脉应用氨甲环酸10 mg/kg,并于手术结束后经引流管向关节腔注射1.0 g氨甲环酸,夹闭引流管4 h,弹力绷带包扎。对照组的处理为给予相应量的生理盐水。观察两组患者术后24 h、48 h引流量并于术后第3天复查血常规。结果 氨甲环酸组术后切口引流量平均约220 mL,与对照组450 mL相比,差异有统计学意义(P < 0.05)。术后第3天复查血红蛋白的降低程度,氨甲环酸组降低约12.9 g/L,明显小于对照组23.5 g/L,且差异有统计学意义(P < 0.05)。结论 氨甲环酸静脉滴注联合关节腔注射可以明显降低初次全膝关节置换患者术后出血量。     

Triterpene esters from <Emphasis Type="Italic">Uncaria rhynchophylla</Emphasis> drive potent IL-12-dependent Th1 polarization

Dendritic cells (DC) are key antigen-presenting cells that link innate and adaptive immunity and ultimately activate antigen-specific T cells. In the current study, we demonstrated that two triterpene esters, uncarinic acid C (1) and uncarinic acid D (2), which are isolated from the hooks of Uncaria rhynchophylla, activate phenotypic and cytokine production alterations in DC. We also show that 1 and 2 modulate human DC function in a fashion that favors Th1 cell polarization. The effect of 1 (E configuration at the 2′ position) was approximately 20 times more potent than that of 2 (Z configuration at 2′). These results indicated that the configuration of the 2′ double bond greatly effects activity. Thus, 1 and 2 may prove useful as DC-based vaccines for cancer immunotherapy.