Anti-inflammatory butenolide derivatives from the coral-derived fungus Aspergillus terreus and structure revisions of aspernolides D and G,butyrolactone VI and 4′,8′′-diacetoxy butyrolactone VI

Chemical investigation of the coral-derived fungus Aspergillus terreus led to the discovery of ten butenolide derivatives (1–10), including four new ones (1–4). The new structures were characterized on the basis of comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Compounds 1 and 2 were a pair of rare C-8′′ epimers with vicinal diol motifs. The absolute configurations of 1–4 were determined via [Mo₂(AcO)₄] induced circular dichroism (ICD) spectra and comparison of their experimental ECD spectra. Importantly, the structures of reported aspernolides D and G, butyrolactone VI and 4′,8′′-diacetoxy butyrolactone VI have been correspondingly revised via a combined strategy of experimental validations, ¹³C NMR predictions by ACD/Labs software, and ¹³C NMR calculations. Herein we provide valuable referenced ¹³C NMR data (C-7′′, C-8′′, and C-9′′) for the structure elucidations of butenolide derivatives with 1-(2-hydroxyphenyl)-3-methylbutane-2,3-diol, 2-(2,3-dihydrobenzofuran-2-yl)propan-2-ol, or 2,2-dimethylchroman-3-ol motifs. Additionally, all the isolates (1–10) were assessed for anti-inflammatory activity by measuring the amount of NO production in lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages, and compound 10 showed an even stronger inhibitory effect than the postive control indomethacin, presenting it as a promising lead compound for the development of new anti-inflammatory agents.

Chemical investigation of the coral-derived fungus Aspergillus terreus led to the discovery of ten butenolide derivatives (1–10), including four new ones (1–4).     

Discovery of acylphloroglucinol-based meroterpenoid enantiomers as KSHV inhibitors from Hypericum japonicum

Kaposi''s sarcoma associated herpesvirus (KSHV) has gained considerable attention as a type of carcinogenic pathogen. Recent research suggests that KSHV has participated in the pathogenesis of Kaposi''s sarcoma-related malignant neoplastic diseases. Viral lytic infection might be pivotal for the etiopathogenesis of KSHV-induced diseases; however, most clinical KSHV lytic replication inhibitors like ganciclovir, nelfinavir, or cidofovir do not restrain virus replication effectively enough to achieve clinical efficacy. In our continued pharmaceutical studies on Chinese herbal medicines, new acylphloroglucinol-based meroterpenoid enantiomers have been discovered from Hypericum japonicum. Most of these metabolites have potential inhibitory activities that target KSHV lytic replication. Amongst these analogues, compounds 1a and 1b possess an unreported ring system cyclopenta[b]chromene. Compounds 1a with 4a exhibit stronger inhibitory activities towards the lytic replication of KSHV in Vero cells. In addition, 1a and 4a have IC₅₀ values of 8.30 and 4.90 μM and selectivity indexes of 23.49 and 25.70, respectively. Qualitative and quantitative SAR and molecular docking studies for acylphloroglucinol-based meroterpenoids with regard to anti-KSHV activity were conducted. An explanation for the variation in the activity and selectivity indexes was proposed in accordance with the predicted binding pose found with molecular docking to a putative target, thymidylate synthase (kTS). Compounds 1a and 4a have potential for further development and optimization of their anti-KSHV activities which could lead to new candidate drugs.

New enantiomers (1a/1b–4a/4b) were discovered from Hypericum japonicum. 1a/1b possessed a novel ring system cyclopenta[b]chromene. 1a and 4a exhibited promising anti-KSHV activities. QSAR studies for enantiomers on anti-KSHV activity were conducted.     

外周血白细胞水平与2型糖尿病的相关性研究

目的　探讨外周血白细胞水平与 2型糖尿病的相关性。方法　分析了 178例初诊的2型糖尿病患者和 85例正常对照者的体重指数 (BMI)、外周血白细胞 (WBC)和糖脂代谢指标。结果　 2型糖尿病组WBC、BMI、空腹血糖 (FBG)、空腹胰岛素 (FINS) ,甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL)均高于对照组 (P <0 .0 5～P <0 .0 1) ,而胰岛素敏感性指数 (ISI)和高密度脂蛋白胆固醇 (HDL)降低 (P <0 .0 5 ) ;Spearman相关分析显示WBC与BMI(r =0 .16,P <0 .0 5 )、FBG(r =0 .17,P <0 .0 5 )、TG(r =0 .2 0 ,P <0 .0 1)、LDL(r =0 .17,P <0 .0 5 )等正相关 ,而与ISI(r =-0 .3 4,P <0 .0 1)和HDL(r =-0 .18,P <0 .0 5 )负相关 ;多元逐步回归分析显示FINS、2小时血糖 (P2hBG)、ISI、TG和HDL是白细胞升高的独立危险因素。结论　白细胞升高与 2型糖尿病糖脂代谢异常相关 ,慢性炎症可能参与了胰岛素抵抗和 2型糖尿病的发生。     

正常胃黏膜上皮细胞原代培养方法

胃黏膜上皮细胞是进行胃生理功能、病变机制、药物治疗等研究的重要工具，已被广泛应用于科学实验。原代培养细胞能反映原始组织的特点，与体内姊妹细胞的生理状态相似，是进行相关研究的理想材料。但胃黏膜上皮细胞对内环境要求较高，分离纯化后并不象肝细胞等易于存活和生长，不少实验因这一环节而不能进行下去，不得不采用从肿瘤组织衍生的各种细胞株，此类细胞株与正常胃黏膜上皮细胞在生长特性、形态结构等方面存在较大差异，不能代表正常胃黏膜上皮。在我国，几乎所有的相关研究都是采用各种细胞株，因此本文较详细全面地介绍了文献报道中较成功的正常胃黏膜上皮细胞原代培养方法，以期对相关研究有所帮助。     

红元胶囊用于跟骨骨折术后效果评价

目的探讨红元胶囊在跟骨骨折术后的应用效果及对患者局部肿胀、术后切口的影响。方法选取医院2016年5月至2018年5月接受手术的跟骨骨折患者104例,按摸球法随机分为对照组和试验组,各52例。两组患者均予跟骨骨折切开复位内固定术,并于术中松止血带前30 min静脉滴注氨甲环酸注射液,试验组患者加服红元胶囊(每日3次,每次3粒),均治疗3个月。结果试验组患者切口疗效总有效率为96.15%,显著高于对照组的73.08%(P<0.05);试验组患者的血液引流总量显著少于对照组,血液引流时间、切口干燥时间和切口愈合时间均显著短于对照组(P<0.05);与术后1 d比较,两组患者术后7 d的踝肿胀和足肿胀程度均显著减轻,且试验组显著优于对照组(P<0.05);两组患者术后治疗过程中均未出现明显不良反应。结论跟骨骨折术后应用红元胶囊可提高切口疗效,缓解局部肿胀程度,促进切口愈合。     

门静脉高压巨脾大部切除后残脾神经分布与定量研究

目的：观察门静脉高压巨脾大部切除后残脾神经纤维分布与密度变化,评估残脾保留的价值。 方法：选取门静脉高压脾肿大行脾大部切除并残脾腹后固定术患者13例,收集患者术后切取的巨脾组织,以及术后8年穿刺获取的残脾组织,另取外伤性脾组织13例为正常对照。采用免疫组化法检测脾神经肽Y（NPY）和神经丝蛋白200（NF 200）阳性神经纤维分布及密度。 结果：3组脾组织NPY和NF200阳性神经纤维的分布部位大致相同,但两者在巨脾组织中的密度明显较高。红髓部分的定量分析显示,巨脾组织NPY与NF200阳性神经纤维密度均明显高于残脾组织和正常脾组织（均P<0.05）,而两种阳性神经纤维密度在残脾组织与正常脾组织间差异无统计学意义（均P>0.05）。 结论：巨脾大部切除术后残脾神经纤维分布及含量与正常脾大致相同,提示解除高压环境后,残脾神经功能能逐渐恢复正常。     

高流体静力压下脾静脉和大隐静脉管壁细胞凋亡变化

目的:观察不同静脉管壁在高流体静力压下细胞凋亡变化及机制。方法:收集高压性病脾静脉(DSV)与曲张大隐静脉(VGSV)标本,分别以正常脾静脉(SV)、正常大隐静脉(GSV)标本为对照。采用TUNEL、免疫荧光观察静脉管壁细胞凋亡情况,免疫组化检测凋亡相关蛋白Bax、Bcl-xl表达,电镜观察超微结构的变化。结果:与各自的对照比较,DSV和VGSV管壁(内膜和中膜)凋亡细胞比率明显降低(均P0.05);促凋亡蛋白Bax表达减少,抗凋亡蛋白Bcl-xl表达增加,Bax/Bcl-xl比值明显降低(均P0.05);DSV和VGSV的内皮细胞与平滑肌细胞出现线粒体嵴模糊、髓样变、核染色质边集。结论:不同的静脉管壁在高流体静力压下均存在相同的经线粒体通路细胞凋亡失调,这可能是导致相关疾病状态下静脉管壁扩张和增厚的重要机制。     

阿帕替尼治疗晚期乳腺癌20例

目的 研究阿帕替尼治疗晚期乳腺癌的临床疗效及预后。方法 2015年5月至2017年6月皖北煤电集团总医院及宿州市立医院经病理学确诊的44例乳腺癌病人中20例口服阿帕替尼,24例行姑息对症支持治疗,比较两组总生存期、无进展生存期、疗效及对口服阿帕替尼不良反应的观察。结果 阿帕替尼组病人的中位总生存期(14个月)及中位无进展生存期(11个月)均长于姑息治疗组(6个月,4个月),两组差异有统计学意义(Kaplan-Meier法,P<0.05);阿帕替尼组病人的疾病控制率(85%)远高于姑息治疗组(46%),两组差异有统计学意义(χ² =14.204,P=0.003);口服阿帕替尼治疗中,不良反应多为1[KG-*3]～2级,治疗过程中无因为不能耐受不良反应而停止阿帕替尼靶向治疗。结论 阿帕替尼治疗一线、二线及三线治疗失败的晚期乳腺癌有较好的临床疗效及生存获益,不良反应可控制,值得临床上广泛应用。     

Identifying optimal heparin management during cardiopulmonary bypass in Chinese people: a retrospective observational comparative study

Traditionally heparin is adapted according to total body weight (TBW) to providing anticoagulation during cardiopulmonary bypass (CPB), but it may be inaccurate in some patients. The medical records of 100 adult patients who received CPB in Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology over a 10-month period in 2017 were included in the retrospective study. An unfractionated heparin (UFH) bolus of 300 IU/kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU/kg) to maintain a target activated coagulation time (ACT) of at least 480 s. We used TBW, ideal body weight (IBW), lean body weight (LBW), or body mass index (BMI) to establish and evaluate a linear model of ACT and the amount of heparin respectively. The linear fit effect of the model based on BMI on the original data is better than the others. As the instruments to measure heparin concentration is unavailable in most medical institutions in China. The new linear model based on BMI is helpful to estimate a more individualized heparin dosage in the heparinized phase and to provide useful reference to the amount of remaining heparin in the neutralization phase.