胃肠道穿孔感染性休克患者肠道菌群及其与血清C反应蛋白和降钙素原的相关性

目的探究胃肠道穿孔感染性休克患者肠道菌群及其与血清C反应蛋白(CRP)、降钙素原(PCT)的相关性。方法选取2017年1月到2019年6月辽宁省人民医院收治的110例胃肠道穿孔致感染性休克患者,按照APACHEII评分分为A组(APACHEII评分<20分,n=67)和B组(APACHEII评分≥20分,n=43)。另选52例同期体检正常的健康者作为正常组。检测各组对象血中免疫细胞数、肠道微生物及血清CRP、PCT水平,并分析患者肠道菌群与血清CRP、PCT水平的相关性。结果各组对象血液中白细胞、中性粒细胞、CD4^+细胞、CD4^+/CD8^+水平均为B组>A组>正常组,差异均有统计学意义(均P<0.05)。各组对象肠道肠杆菌数量为B组>A组>正常组,双歧杆菌数量及B/E值均为B组A组>正常组,差异均具有统计学意义(均P<0.05)。Pearson相关性分析显示,双歧杆菌数量、B/E值与血清CRP、PCT分别呈负相关(r=-0.624,-0.746;-0.638,-0.757,均P<0.05)。结论胃肠道穿孔感染性休克患者存在以双歧杆菌减少和肠杆菌增加为主要特点的肠道菌群失衡,且双歧杆菌数量和B/E值与血清CRP、PCT水平具有一定相关性,推测肠道菌群可能参与了疾病的发生和发展过程。     

肝硬化患者益生菌干预效果及肠道菌群变化分析

目的探讨肝硬化患者口服双歧杆菌四联活菌片后肠道优势菌群变化以及对肝功能、内毒素等指标的影响。方法入组乙肝后肝硬化患者62例,分为治疗组和对照组,两组患者均予以肝硬化常规治疗,治疗组在此基础上予双歧杆菌四联活菌片口服,1.5g/次,3次/d,连用30d。结果治疗1个月后,两组患者的谷草转氨酶、谷丙转氨酶、凝血酶原时间均降低(治疗组:t=5.61,t=5.25,t=2.89;对照组:t=4.76,t=2.75,t=1.82,P0.05或P0.01),且治疗组患者下降的幅度更明显(t=2.16,t=4.50,t=1.80,P0.05或P0.01)。治疗组患者内毒素水平降低(t=4.18,P0.01),而对照组患者内毒素下降差异无统计学意义。定量PCR结果显示治疗组患者中双歧杆菌属、乳酸杆菌属、柔嫩梭菌、数量显著上升,肠杆菌属数量显著下降(t=8.06,t=4.38,t=5.09,t=-14.35,P0.01)。肝硬化患者肠道定植抗力B/E值与血浆内毒素水平呈现显著负相关(r=-0.63,P0.01)。结论口服双歧杆菌四联活菌片能调节肝硬化患者的肠道菌群,形成紧密的生物学屏障,进而降低血浆内毒素水平,改善肝功能,发挥显著的辅助治疗作用。     

老年房颤患者肠道菌群变化及其影响因素

目的探讨老年房颤患者肠道菌群变化及影响菌群变化的相关因素。方法回顾性收集20例老年房颤患者作为房颤组,并选取性别、年龄与患者匹配的30例老年健康体检者作为对照组,分析两组对象肠道优势菌的特点。同时收集房颤组患者C反应蛋白(CRP)、总胆汁酸(TBA)、同型半胱氨酸(Hcy)、B型纳尿肽(BNP)、左室射血分数数值(LVEF)等检测结果,分析上述因素与肠道优势菌群的关系。结果房颤组患者直肠真杆菌数量为(4.66±1.62)lg copies/g粪便,低于对照组的(6.10±1.44)lg copies/g粪便,差异有统计学意义(t=-3.286,P=0.002)。房颤组患者肠道普拉梭菌、肠球菌、类杆菌、乳杆菌、双歧杆菌、柔嫩梭菌、酪酸梭菌、Atopobium cluster(Ato)、肠杆菌数量及双歧杆菌/肠杆菌(B/E)值与对照组比较差异无统计学意义(均P0.05)。在房颤组中,CRP升高患者肠道双歧杆菌数量和B/E值显著高于CRP正常患者,CRP升高与双歧杆菌数量呈正相关(r=0.651,P=0.002);Hcy升高患者肠道肠杆菌数量显著高于Hcy正常患者,Hcy升高与肠杆菌数量呈正相关(r=0.567,P=0.009)。BNP、TBA、LVEF与优势菌群无显著相关性。结论老年房颤患者存在肠道菌群失调。CRP、Hcy和老年房颤患者肠道菌群具有一定的相关性。     

胆囊切除术后腹泻患者应用双歧三联活菌胶囊改善其肠道微生态紊乱的效果评价

目的探讨双歧三联活菌胶囊对胆囊切除术后腹泻(PCD)患者的临床疗效及对肠道菌群的影响。方法选取胆囊切除术后腹泻患者80例,随机分为观察组和对照组,每组40例。对照组患者给予常规治疗,观察组患者在对照组的基础上给予双歧三联活菌胶囊口服治疗(420mg/次,3次/d),连用4周。比较两组患者治疗后的临床疗效及不良反应,并检测两组患者治疗前后肠道菌群组成及血清D-乳酸和5-HT的水平。结果治疗后,观察组患者的总有效率为92.50%,显著高于对照组的70.00%(χ~2=6.646,P0.05),两组患者均无明显不良反应。与对照组患者相比,观察组双歧杆菌和乳酸杆菌数量显著增加[logCFU/g:(9.88±1.01)vs(7.35±0.72),(8.96±0.69)vs(7.61±0.58),t=12.9004、9.4722,P0.01],大肠埃希菌和肠球菌数量下降[logCFU/g:(7.86±0.81)vs(8.41±0.80),(8.06±0.69)vs(8.56±0.78),t=-2.9626、-3.0366,P0.01]。观察组患者血清D-乳酸和5-HT的水平明显低于对照组[(5.69±0.76)μg/mL vs(8.12±0.92)μg/mL,(1.24±0.21)ng/mg vs(1.68±0.19)ng/mg,t=-12.8790、-9.8264,P0.01]。结论双歧三联活菌胶囊治疗胆囊切除术后腹泻患者疗效确切,可降低患者血清D-乳酸和5-HT的水平,纠正患者肠道微生态失衡。     

单核细胞趋化蛋白-1、高迁移率族蛋白B1与 溃疡性结肠炎患者肠道菌群变化的相关性

目的探讨单核细胞趋化蛋白-1(MCP-1)、高迁移率族蛋白B1(HMGB1)与溃疡性结肠炎(UC)患者肠道菌群变化的相关性。方法选取2016年9月-2018年1月遂宁市中心医院收治的98例UC患者资料,根据Mayo评分系统将UC患者分为活动期组(n=50)和缓解期组(n=48)。选取同期进行体检的健康人50例作为对照组。比较各组间肠道菌群,血清MCP-1、HMGB1水平,并进行Pearson相关分析。结果活动期组患者肠道乳杆菌、双歧杆菌含量[(5.34±0.87)、(5.81±0.83)CFU/g]显著低于缓解期组和对照组[(8.07±0.86)、(8.35±0.88)CFU/g;(8.13±0.91)、(8.46±0.95)CFU/g](F=12.035,P0.001;F=10.472,P0.001),大肠埃希菌、肠球菌、拟杆菌含量[(11.75±1.24)、(7.91±0.92)、(5.26±0.62)CFU/g]显著高于缓解期组和对照组[(7.92±1.09)、(4.94±0.61)、(3.30±0.52)CFU/g;(7.64±1.02)、(4.83±0.56)、(3.14±0.47)CFU/g](F=10.815,P0.001;F=9.796,P0.001;F=9.713,P0.001),缓解期组和对照组研究对象各肠道菌群比较差异无统计学意义(P0.05)。活动期组和缓解期组患者血清MCP-1、HMGB1水平[(267.42±23.51)、(21.35±2.26)ng/mL;(188.15±20.73)、(6.28±1.38)ng/mL]显著高于对照组[(106.38±15.92)、(2.13±0.41)ng/mL](F=84.163,P0.001;F=25.386,P0.001);活动期组患者血清MCP-1、HMGB1水平[(267.42±23.51)、(21.35±2.26)ng/mL]显著高于缓解期组[(188.15±20.73)、(6.28±1.38)ng/mL](t=17.676、39.641,均P0.05)。经过Pearson相关性分析,MCP-1、HMGB1与UC患者乳杆菌、双歧杆菌含量呈负相关(r=-0.715、-0.659,r=-0.703、-0.614,均P0.001),与大肠埃希菌、肠球菌、拟杆菌含量呈正相关(r=0.783、0.702,r=0.762、0.735,r=0.653、0.612,均P0.001)。结论 MCP-1、HMGB1作为促炎因子可介导肠黏膜炎性反应,引起UC患者肠道菌群紊乱。     

肠道菌群及代谢与载脂蛋白E在动脉粥样硬化中的相互作用

目的明确肠道菌群及代谢与载脂蛋白在动脉粥样硬化中的相互作用。方法 C57BL/6J小鼠作为对照组(n=5),载脂蛋白E基因敲除(apolipoprotein E-deficient mice,ApoE~(-/-))小鼠作为动脉粥样硬化模型组(n=8),均为6周龄雄性。两组小鼠均给予高脂饮食,饲养12周后麻醉、摘眼球取血,采用全自动生化分析仪检测血脂,高效液相色谱串联质谱法测定血浆氧化三甲胺(Trimethylamine N-oxid,TMAO)的含量,留取粪便用于肠道菌群16S rRNA V3-V4区域的测序进行菌群鉴定,油红"O"染色主动脉根部确定动脉粥样硬化斑块面积。结果血清学指标:ApoE~(-/-)小鼠较对照组血浆中TMAO(t=-2.87,P0.05)、LDL(t=-11.76,P0.05)、TG(t=-3.56,P0.01)、TC(t=-12.38,P0.01)含量及动脉粥样硬化斑块面积(t=-11.94,P0.01)显著增加,HDL含量降低(t=3.63,P0.01)。肠道菌群测序:两组小鼠随着动脉斑块面积的增加,肠道微生物的丰富度、物种组成及功能预测分析等差异均有统计学意义,还发现ApoE~(-/-)小鼠能够生成TMAO的肠道菌群包括Anaeroplasma、Anaeroplasmatales、Anaeroplasmataceae、Proteus、Paraprevotella和Paraprevotellaceae,而对照组生成TMAO的菌群只有1类,为Anaerotruncus。结论 C57BL/6J小鼠与ApoE~(-/-)小鼠肠道微生物群落的组成、功能及其代谢产物TMAO的血浆含量各不相同,提示ApoE基因缺乏的宿主除导致脂质代谢紊乱外,在动脉粥样硬化形成过程中一定程度上影响着肠道菌群的代谢。     

急性心肌梗死患者肠道菌群多样性分析

目的初步探究急性心肌梗死患者肠道菌群的多样性。方法选择2015年6月至2016年3月于大连大学附属中山医院住院治疗的急性心肌梗死患者作为观察组,年龄51~70岁。选择同期经冠脉造影排除冠心病的住院患者为对照组,年龄51~70岁。排除近1个月内发生感染、炎性肠病及应用抗生素的患者。所有患者按性别与年龄分为A、B、C、D组。直接从患者粪便标本中提取细菌总DNA,PCR扩增后进行梯度凝胶电泳(DGGE)分析。结果 DGGE分析显示急性心梗患者肠道菌群丰度均较对照组下降。A组中观察组与对照组患者电泳条带数为(33.71±4.39)vs(38.71±2.56),t=-2.058,P=0.040;C组患者为(31.14±2.67)vs(35.29±3.55),t=-2.005,P=0.045;差异均具有统计学意义。B与D组中心梗患者肠道菌群丰度亦有下降趋势,但与对照组比差异无统计学意义。UPGAM法聚类分析显示除D组外,各组中观察组与对照组患者肠道菌群呈现分离现象;急性心梗患者肠道菌群有较高相似性,与非冠心病患者肠道菌群差异明显。结论急性心梗与非冠心病患者肠道菌群存在差异,急性心梗患者肠道菌群多样性较低。肠道菌群改变可能与急性心肌梗死存在一定相关性。     

葛根芩连汤对肠道湿热证泄泻小鼠肠道微生物的影响

目的探讨葛根芩连汤对肠道湿热证泄泻小鼠肠道微生物的影响。方法造模:10只KM雄性小鼠随机分为正常组5只和模型组5只,采用"高糖高脂+高温高湿+白酒复合灌胃冰水"的方法制备肠道湿热证泄泻小鼠模型。治疗:15只KM雄性小鼠随机分为正常组5只和模型组10只,造模成功后将模型组小鼠分为自愈组和治疗组,治疗组小鼠运用葛根芩连汤进行治疗,分别在造模和治疗后无菌采集小鼠肠道内容物进行微生物培养。结果造模后,小鼠出现懒动、肛温升高、体重增长缓慢、黄褐色稀便、肛门污秽等湿热泄泻症状,肠道乳杆菌数高于正常组,而细菌总数、肠杆菌、双歧杆菌、B/E值降低,其中细菌总数以及双歧杆菌数与正常组相比差异有统计学意义(t=14.182,P0.001;t=2.797,P=0.049)。经葛根芩连汤治疗后,小鼠肠道乳杆菌和双歧杆菌数高于正常组,而细菌总数、肠杆菌数低于正常组,且乳杆菌数和肠杆菌数与正常组相比差异有统计学意义(t=-5.210,P=0.033;t=-11.160,P=0.008),B/E值与正常组差异无统计学意义(t=-1.427,P=0.227)。结论造模使小鼠肠道双歧杆菌数显著降低,B/E值下降;葛根芩连汤可促进肠道湿热证泄泻小鼠肠道乳杆菌和双歧杆菌的增生,提高B/E值。     

慢传输型便秘患者肠道粪便菌群的变化特征

目的通过16S rDNA高通量测序技术,研究慢传输型便秘(slow transit constipation,STC)患者粪便菌群的变化特征。方法选取12例慢传输型便秘患者(STC组)及12例健康志愿者(对照组),留取粪便标本后,应用16S rDNA高通量测序技术对标本进行测序,并分析测序结果。结果 STC组与对照组人群肠道在菌群物种种类(Chao1指数和Sobs指数)上差异存在统计学意义(Z=-2.771,P=0.006;Z=-2.425,P=0.015),对照组人群肠道菌群物种种类明显高于STC组;两组在物种均一性(Shannon指数、Simpson指数)上差异无统计学意义(Z=-0.520,P=0.603;Z=-0.348,P=0.728)。在门水平,两组人群粪便菌群多样性差异无统计学意义。在属水平,Phascolarctobacterium(Z=-2.194,P=0.028)、Streptococcus(Z=-4.157,P0.001)、Eggerthella(Z=-2.427,P=0.015)和Actinomyces(Z=-2.310,P=0.021)在STC组人群肠道中相对丰度增加,而Faecalibacterium(Z=-2.887,P=0.004)、Roseburia(Z=-3.118,P=0.002)、Sphingomonas(Z=-4.157,P0.001)、Variovorax(Z=-2.732,P=0.006)、Holdemania(Z=-1.970,P=0.049)、Phyllobacterium(Z=-2.732,P=0.006)、Pseudomonas(Z=-2.439,P=0.015)、Acinetobacter(Z=-2.732,P=0.006)、Aquabacterium(Z=-2.134,P=0.033)和Novosphingobium(Z=-2.134,P=0.033)在STC组中相对丰度减少。结论 STC组与对照组人群肠道在菌群物种种类丰富度上差异存在统计学意义,而在菌群分布均一性上差异无统计学意义;在菌属水平,两组人群的粪便菌群构成也存在较大差异。     

儿童功能性便秘患者肠道菌群及血清脑肠肽水平的变化

目的探讨儿童功能性便秘(FC)患者肠道菌群及血清脑肠肽水平的变化。方法选取2017年1月至2019年4月在我院儿科门诊治疗的80例FC患儿为研究组,选择同期于体检中心检查的无胃肠道疾病的30例健康儿童为健康组。研究组患儿根据病情轻重分为轻中度组(52例)和重度组(28例)。比较各组儿童肠道菌群数量[乳杆菌、双歧杆菌和大肠埃希菌]及血清脑肠肽指标[一氧化氮(NO)、P物质(SP)和血管活性肠肽(VIP)]水平的差异。结果研究组患儿肠道双歧杆菌[(8.16±0.89)lg CFU/g]和乳杆菌数量[(7.92±0.83)lg CFU/g]明显少于健康组[(8.94±0.97)lg CFU/g、(8.63±0.91)lg CFU/g],而大肠埃希菌数量[(8.12±0.81)lg CFU/g]明显多于健康组[(7.30±0.72)lg CFU/g],差异有统计学意义(t=2.37、2.35、2.44,P0.05)。重度组患儿肠道双歧杆菌和乳杆菌数量明显少于轻中度组,而大肠埃希菌数量明显多于轻中度组(t=2.36、2.34、2.29,P0.05)。研究组患儿血清NO和VIP水平[(50.12±8.25)μmol/L、(29.17±5.12)pg/mL]明显高于健康组[(34.46±6.13)μmol/L、(20.43±4.79)pg/mL],SP水平[(5.21±0.82)ng/mL]明显低于健康组[(7.57±1.04)ng/mL],差异有统计学意义(t=2.78、2.54、2.47,P0.05)。重度组患儿血清NO和VIP水平高于轻中度组,SP水平明显低于轻中度组(t=2.31、2.41、2.23,P0.05)。结论 FC患儿存在肠道菌群失调和脑肠肽分泌异常,且随着病情的加重其肠道菌群失调及脑肠肽分泌异常越发明显。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.