HPV感染对患者阴道菌群及妊娠结局的影响

目的研究HPV感染对患者阴道菌群以及妊娠结局的影响。方法选择2017年9月至2018年9月在本院定期产检的孕妇,根据妊娠结局将孕妇分为正常妊娠组和不良妊娠组。收集两组患者一般资料及其阴道样本进行微生物检测及分析。结果不良妊娠组患者中HPV阳性患者比例明显高于正常妊娠组,正常妊娠组中HPV阴性和HPV阳性患者及不良妊娠组中HPV阴性患者阴道中乳杆菌(Lactobacillus)丰度最高,其次是加德纳菌(Gardnerella),普氏菌(Prevotella)和纤毛球菌(Sneathia)。不良妊娠组中HPV阳性患者阴道中乳杆菌(Lactobacillus)丰度最高,其次是加德纳菌(Gardnerella),芽孢杆菌(Bacillus),巨球菌(Megasphaera)和链球菌(Streptococcus)。不良妊娠组HPV阳性患者阴道中链球菌、巨球菌和芽孢杆菌丰度明显高于HPV阴性患者,乳杆菌和奇异菌(Atopobium)丰度明显低于HPV阴性患者。结论 HPV感染女性更易产生不良妊娠结局,其机制可能是HPV降低了阴道中乳杆菌丰度,增加阴道微生物群多样性和丰富度。     

人乳头瘤病毒阴性宫颈癌患者阴道菌群多样性CSCD

目的 通过研究人乳头瘤病毒(human papillomavirus,HPV)阴性宫颈癌患者的阴道菌群多样性,探索HPV阴性宫颈癌与阴道菌群的关系。方法 选择38例HPV阴性(HPV_negative)宫颈癌患者、38例HPV阳性(HPV_positive)宫颈癌患者和34例正常对照(Normal_contorl)者的阴道分泌物,采用16S rDNA高通量扩增测序技术检测阴道菌群,并进行生物信息学分析,获得各组对象菌群构成及丰度信息,分析组间差异性。结果 110例阴道分泌物样本共中检测出743个可操作分类单位(operational taxonomic units,OTUs)。各组菌群丰度排名前5位的门类为厚壁菌门(Firmicutes)、放线菌门(Actinobacteria)、变形菌门(Proteobacteria)、拟杆菌门(Bacteroidetes)、梭菌门(Fusobacteria)。Alpha多样性分析显示单个样本间差异无统计学意义(均P>0.05)。Beta多样性分析显示组间菌群差异有统计学意义(MRPP分析:加权P=0.022,非加权P=0.001)。LEfSe分析显示在不同分组中有显著作用的微生物类群有43种,其中Normal_contorl有15种,HPV_negative有23种,HPV_positive有5种。组间秩和分析显示对组间划分产生显著性影响的物种有49个(均P<0.05),其中属水平有28个(均P<0.05)。宫颈癌患者伯克霍尔德菌属丰度(HPV_negative:13.852%、HPV_positive:8.886%)高于正常对照组(0.058%)。正常对照组乳杆菌属丰度(44.326%)高于宫颈癌组(HPV_negative:14.778%、HPV_positive:19.735%)。结论 HPV阴性宫颈癌患者阴道菌群的多样性相对于健康女性阴道菌群更为复杂,其中乳杆菌属丰度下降,厌氧菌减少,需氧菌增加。相对于HPV阳性宫颈癌患者,HPV阴性宫颈癌患者阴道菌群多样性增加,乳杆菌丰度下降。HPV阴性宫颈癌患者阴道菌群多样性更为复杂,其与宫颈癌发生发展的关系有待深入研究。     

阴道微生物群和雌激素及孕激素水平对宫颈病变的影响CSCD

目的 研究阴道微生物群、雌激素、孕激素水平与宫颈病变的关系,评价宫颈病变的高危因素,为该类患者的治疗提供参考。方法 选择2021年12月至2022年5月我院首次确诊的宫颈病变患者121例为研究组。全部患者行病理活检,其中宫颈低级别鳞状上皮内病变(LSIL)93例,宫颈高级别鳞状上皮内病变(HSIL)16例,宫颈鳞状细胞癌7例,腺癌5例。随机选取同期筛查无宫颈病变的健康女性100例作为正常对照组。两组对象同时进行阴道微生物群分析、人乳头瘤病毒(HPV)和雌、孕激素水平检测,采用Logistic逐步回归法分析其与宫颈病变的相关性。结果 (1)宫颈病变组患者阴道微生物群异常率(82.64%)显著高于正常对照组(32.00%),其中乳杆菌阳性率(28.93%)显著低于正常对照组(81.00%),阴道菌群密集度异常率(55.37%)显著高于正常对照组(3.00%),阴道菌群多样性异常率(66.12%)显著高于正常对照组(21.00%),HPV感染率(72.73%)显著高于正常对照组(25.00%),差异均有统计学意义(均P<0.05);(2)宫颈病变组患者雌二醇水平显著高于对照组(P<0.05),而孕酮水平差异无统计学意义(P>0.05);(3)二分类Logistic回归分析显示,乳杆菌减少、HPV感染和雌激素水平均为影响宫颈病变的独立危险因素(均P<0.05)。结论阴道微生物群失调(阴道菌群密集度异常、阴道菌群多样性异常、阴道优势菌改变、HPV感染),雌、孕激素水平改变与宫颈病变有密切相关性;同时阴道乳杆菌减少、HPV感染与雌激素水平下降是引起宫颈病变的独立危险因素。     

门诊阴道镜检查患者阴道菌群构成与HPV16感染的关系

目的探讨门诊阴道镜检查患者阴道菌群构成与HPV16感染的关系。方法选取我院2016年3月-2018年12月门诊阴道镜检查的高危HPV感染患者96例为研究对象,通过阴道镜检查结果分析其HPV16感染情况、阴道菌群构成及菌群多样性。结果 HPV16阳性组人数41例,阴性组55例,感染率为42.7%。HPV16阳性组患者阴道菌群中占前5位的是乳酸杆菌属、加德纳菌属、嗜胨菌属、纤毛菌属及普氏菌属,阴性组占前5位的分别为乳酸杆菌属、加德纳菌属、奇异菌属、嗜胨菌属及卟啉单胞菌属。HPV16阳性组乳酸杆菌属构成比显著小于HPV阴性组,差异具有统计学意义(P=0.007,χ²=7.195),两组加德纳菌属、嗜胨菌属构成比无差异(P=0.073,χ²=3.217;P=0.763,χ²=0.091)。HPV16阳性组菌群Shannon指数、ACE指数、Chaol指数显著大于阴性组,差异具有统计学意义(P=0.014,χ²=2.461;P=0.002,χ²=3.025;P<0.001,χ²=4.534);Simpson指数比较差异无统计学意义(P=0.310,χ²=0.406)。结论阴道菌群结构的改变主要表现为乳酸杆菌属数量的减少及加德纳菌属、嗜胨菌属、普氏菌属及纤毛菌属的增加,这可能与HPV16感染有一定关系。     

阴道菌群与女性不孕症的相关性

摘要：目的 探索阴道菌群结构与女性不孕症的相关性。方法 选择2018年4月于南京市东南大学附属中大医院生殖中心新确诊的15例不孕患者作为不孕组,同期体检的15例有生育史的健康育龄妇女为对照组。两组研究对象均填写统一的调查问卷,并于阴道后穹窿处采集阴道拭子。提取样本总基因组DNA,对16S rRNA基因V3?V4区高通量测序,通过生物信息学分析,比较两组对象阴道菌群结构差异。结果 不孕组和对照组研究对象的阴道菌群α多样性差异无统计学意义。β多样性箱型图及偏最小二乘法判别分析均显示两组菌群结构差异有统计学意义（P<0.05）。不孕组乳杆菌属的相对丰度（81.28%）显著低于对照组（98.63%）（t=1.712,P=0.049）;而纤毛菌属的相对丰度高于对照组,差异有统计学意义（t=2.513,P=0.009）。不孕组加德纳菌属、奇异菌属、普氏菌属和气球菌属相对丰度较对照组增加,但差异无统计学意义（P>0.05）。结论 不孕女性与正常有生育史女性阴道菌群结构存在差异,主要表现为乳杆菌属相对丰度的降低。这种改变可能影响受孕环境,从而成为女性不孕的原因之一。     

宫颈癌术后HPV持续感染者阴道微生态状况分析

目的通过宫颈癌术后HPV持续感染者阴道微生态状况分析,探讨发病的特点,为恢复阴道微生态平衡,HPV转阴,提供治疗依据。方法对75例(肿瘤组)宫颈癌术后HPV持续感染者取阴道分泌物,并取50例绝经期体检妇女作为对照组。结果发现肿瘤组阴道微生态失调占72.0%,优势菌占50.7%,菌群密集度++~+++为46.7%,菌群多样性++~+++为42.7%,pH值≤4.5为28.0%;与对照组比较差异有统计学意义(P0.05)。肿瘤组≤55岁组阴道优势菌占59.1%,与55岁组比较差异有统计学意义(P0.05),其余阴道菌群密集度、菌群多样性、pH、阴道微生态失调、VVC、BV差异无统计学意义。结论 (1)肿瘤组阴道微生态失调;(2)肿瘤组内55岁组的阴道优势菌有更明显差异;(3)评价宫颈癌术后HPV持续感染阴道微生态的状况,对治疗纠正微生态,及HPV的转阴有重要的指导意义。     

高级别宫颈上皮内瘤变术后转归与阴道微生态的相关性研究

目的研究高危型人乳头瘤病毒(HR-HPV)持续感染的高级别宫颈上皮内瘤变(CIN)女性行宫颈锥切术后HPV病毒感染转归与阴道微生态的相关性。方法选取2015年12月至2018年12月我院342例行宫颈锥切术的CINⅡ以上患者(术前HR-HPV检测均为阳性)为研究对象,根据术后1年随访HR-HPV感染转归分为持续阳性组58例,阴性组284例,对比两组研究对象术后1年阴道微生态检测的情况。结果持续阳性组在菌群密集度、菌群多样性及优势菌构成上与阴性组差异存在统计学意义(χ~2=13.711、37.120、25.312,P=0.001、0.001、0.001),持续感染组菌群密集度Ⅳ级构成比、菌群多样性Ⅳ级构成比均高于阴性组,优势菌为革兰阳性大杆菌低于阴性组。Nugent评分构成、pH值构成比两组差异无统计学意义(P0.05)。结论 HR-HPV的持续感染与阴道微生态平衡关系密切,在高级别CIN患者术后应注意纠正阴道微生态平衡,增强宫颈的局部免疫有利于宫颈癌的防治。     

乳杆菌属细菌对宫颈上皮内瘤变患者阴道菌群的影响

目的分析乳杆菌属细菌对宫颈上皮内瘤变(CIN)患者阴道菌群的影响,为该类患者的治疗提供参考。方法选择2019年1月至2020年1月我院收治的CIN患者137例,根据组织学病理结果分为CIN Ⅰ组(84例)和CIN Ⅱ、Ⅲ组(53例)。选择同期100例宫颈检查正常者为对照组。比较各组对象阴道菌群数量。根据患者阴道内乳杆菌数量将患者分为高数量组和低数量组,比较2组患者阴道菌群数量。结果CIN Ⅰ组患者阴道厚壁菌门数量低于CIN Ⅱ、Ⅲ组和对照组,而放线菌门数量高于CIN Ⅱ、Ⅲ组和对照组(均P<0.05)。CIN Ⅱ、Ⅲ组患者阴道乳杆菌属数量高于CIN Ⅰ组和对照组(均P<0.05)。CIN Ⅰ组患者阴道加德纳菌属、奇异菌属数量高于CIN Ⅱ、Ⅲ组和对照组(均P<0.05)。对照组对象阴道菌群Chao、ACE指数均低于CIN Ⅰ组和CIN Ⅱ、Ⅲ组(均P<0.05),同时CIN Ⅱ、Ⅲ组患者阴道菌群Chao、ACE指数均低于CIN Ⅰ组(均P<0.05)。高数量组患者阴道加德纳菌属、奇异菌属占比均低于低数量组(均P<0.05)。结论阴道中乳杆菌属数量的改变易影响阴道菌群,使其抗感染能力下降,增加女性CIN的风险。     

高危型人乳头瘤病毒持续感染患者阴道菌群与 宫颈局部免疫功能改变

目的研究高危型人乳头瘤病毒(hr-HPV)持续感染患者阴道菌群及宫颈免疫功能的变化特点,为宫颈癌的防治提供临床研究资料。方法选择286例连续2年同一型别hr-HPV阳性女性患者为观察组,124例hr-HPV阴性女性患者为对照组,比较两组患者阴道乳杆菌、支原体、衣原体、霉菌检出情况及细菌性阴道病、滴虫感染的差异,并比较两组患者宫颈分泌物物CD~+_4 T、CD~+_8 T细胞检测情况。结果观察组患者中单一型别感染214例(74.83%),2种及2种以上hr-HPV型别复合感染者72例(25.17%)。观察组患者中检出HPV16型165例(45.21%)、HPV18型36例(9.86%)、HPV31型31例(8.49%)、HPV33型22例(6.03%)、HPV51型12例(3.29%)、HPV52型75例(20.54%)、HPV53型15例(4.11%)、HPV58型9例(2.47%)。观察组患者阴道乳杆菌检出率低于对照组,而沙眼衣原体、解脲支原体、细菌性阴道病检出率均高于对照组,差异有统计学差异(P0.05)。观察组患者CD~+_4 T细胞水平(%)及CD~+_4/CD~+_8水平均低于对照组,差异有统计学意义(P0.05)。结论 hr-HPV病毒持续感染患者阴道菌群发生改变,导致宫颈微环境稳态被打破,宫颈局部免疫防御能力降低而成为宫颈癌变的主要促进因素。     

重组人干扰素α2b凝胶联合乳酸菌阴道胶囊对宫颈高危型HPV持续感染的治疗

目的观察重组人干扰素α2b凝胶联合乳酸菌阴道胶囊治疗宫颈高危型人乳头瘤病毒(highrisk human papillomavirus,HPV)持续感染的临床效果。方法将110例宫颈高危型HPV持续感染而液基细胞学检查阴性的患者随机分为两组,其中对照组(58例)予以重组人干扰素α2b凝胶治疗,观察组(52例)予以重组人干扰素α2b凝胶联合乳酸菌阴道胶囊治疗,两组患者均连续治疗3个月经周期。比较两组患者HPV转阴率及阴道微生态改善情况。结果观察组患者治疗总有效率(82.69%)高于对照组(63.79%),差异有统计学意义(χ²=4.937,P=0.026)。治疗后,两组患者阴道微生态失调率均有所下降,且观察组改善情况更为显著(均P<0.05)。治疗后观察组患者阴道菌群密集度及多样性显著低于治疗前,其微生物功能指标优于对照组,乳杆菌定植率高于对照组,病原菌检出率低于对照组(均P<0.05)。结论在重组人干扰素α2b凝胶治疗的基础上联合应用乳酸菌阴道胶囊能明显提高宫颈高危型HPV持续感染的转阴率,其中促进阴道微生态恢复平衡可能是其发挥作用的机制之一。     

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.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.