基于Web of Science的阴道菌群研究现状和热点的可视化分析与展望

探索阴道菌群近10年来的研究现状并预测其发展趋势。

在Web of Science数据库中检索近10年阴道菌群相关的文献,运用可视化软件VOSviewer进行共词分析、文献耦合、合著分析等。

阴道菌群领域发文量呈整体上升趋势,目前的主要热点研究分为阴道菌群的多样性、传染病学、细胞生物和基因学、阴道菌群与生殖的关联四大方面。

文献可视化研究展现了阴道菌群的研究现状和发展趋势,为相关研究人员提供了借鉴。

     

不同方案阴道乳杆菌活菌胶囊结合抗菌药物治疗混合性阴道炎的临床研究

研究两种阴道乳杆菌活菌胶囊结合抗菌药物对混合性阴道炎的疗效。

选取2015年4月至2020年12月北京大学第一医院收治的混合性阴道炎患者50例。同时符合以下两项即确诊为混合性阴道炎：（1）阴道分泌物真菌检测阳性;（2）阴道分泌物革兰染色积分法评分（Nugent评分）≥7分;（3）阴道分泌物滴虫镜检阳性。入选患者根据乳杆菌胶囊使用方法分为联合组（25例）及序贯组（25例）,联合组在使用抗菌药物的同时使用阴道乳杆菌活菌胶囊,序贯组在使用抗菌药物结束后序贯使用阴道乳杆菌活菌胶囊。评估两组患者病原体转阴率、症状改善及乳杆菌恢复情况。

序贯组患者综合治愈率高于联合组（56.0% vs 28.0%,P＜0.05）。经过治疗后,联合组有12.0%的患者阴道菌群恢复为形态类似乳杆菌的革兰阳性大杆菌,序贯组有32.0%恢复为形态类似乳杆菌的革兰阳性大杆菌,两组差异无统计学意义（P＞0.05）,但序贯组在趋势上高于联合组。

对于混合性阴道炎的治疗来说,抗菌药物治疗后序贯使用阴道乳杆菌活菌胶囊优于抗菌药物治疗同时联合使用阴道乳杆菌活菌胶囊。

     

两种乳杆菌联用在食蟹猴阴道的定植效率及其毒性分析

研究乳杆菌鼠李糖乳杆菌-格氏乳杆菌联用制剂(LACT)的定植效率, 评估其有效剂量在动物体内的急性和长期毒性。

在食蟹猴中进行2轮阴道定植试验, 通过检测阴道分泌物pH值和清洁度, 并分离鉴定分泌物中的乳杆菌, 确定乳杆菌联用制剂的定植率和定植剂量; 通过单次和多次阴道给药, 检测联用制剂对食蟹猴体质量、食量、生殖器官及生化指标等的影响, 检测联用制剂在体内的急性和长期毒性。

联用制剂在食蟹猴中连续阴道给药5 d后能成功定植, 改善阴道的微生态; 甲硝唑预处理能够提高定植效率和定植时间; 联用制剂对食蟹猴不具有急性和长期的毒性作用。

在动物模型中, 2种乳杆菌联用制剂对细菌性阴道病具有良好的治疗潜质。

     

近20年阴道菌群的知识结构和发展趋势——基于CiteSpace的文献计量分析

分析阴道菌群研究动态与热点,为其相关研究提供更全面的视角。

以Web of Science为来源数据库,运用CiteSpace.6.1.R2软件绘制文献的作者、机构、国家合作网络图谱以及关键词共现、聚类、突现图谱并进行分析。

共纳入文献4 624篇;美国和华盛顿大学分别是最高产的国家和机构。关键词聚类形成10大板块;获得20个引用爆发的关键词。

阴道菌群的研究热点集中在微生物特征和研究、对疾病的影响及菌群失调的诊治三大方面;阴道菌群与人乳头瘤病毒感染、艾滋病病毒感染及肠道菌群的相互关系在一定时期内为研究前沿。

     

清消法对痤疮患者面部皮肤微生态的调节作用

通过观察皮肤酸碱度、皮脂分泌率、皮损部细菌密度、多样性和局部IL-1、IL-6水平,探讨清消法对寻常型痤疮患者面部微生态的影响。

选择我院收治的寻常型痤疮患者142例,按照随机数字表分成治疗组和对照组,各71例。对照组患者口服异维A酸联合外涂阿达帕林凝胶、夫西地酸乳膏;治疗组患者采用清消法联合外涂阿达帕林凝胶、夫西地酸乳膏进行治疗。观察两组患者的临床疗效、痤疮综合分级系统（GAGS）评分、面部皮肤酸碱度、皮脂分泌率、皮损部细菌密度和多样性及皮损局部IL-1、IL-6水平。

治疗组患者的总有效率（92.96%）高于对照组（81.69%）。与对照组比较,治疗组患者GAGS评分、皮肤酸碱度、皮脂分泌率、皮损部细菌密度及IL-1、IL-6水平均显著降低（均P＜0.05）。

清消法可通过调节面部油脂分泌和酸碱度,改善患者皮损部菌群失衡,降低炎症因子,从而有效治疗痤疮。

     

YNS益肤面霜对豚鼠皮肤变态反应及肠道菌群的影响

建立豚鼠皮肤变态反应模型,并使用YNS益肤面霜对皮肤变态反应模型进行干预,探讨这种面霜对改善及修复受损皮肤的作用及其对豚鼠肠道菌群的影响。

豚鼠24只,随机分成4组：对照组、阳性组、化妆品组和治疗组,每组6只。致敏接触后进行激发反应。提取4组豚鼠粪便标本DNA,使用16S rRNA高通量测序检测肠道菌群构成。

治疗组豚鼠皮肤致敏率为16.7%。益肤面霜治疗对肠道菌群alpha多样性影响不大,但有降低厚壁菌门（Firmicutes）与拟杆菌门（Bacteroidetes）比值（F/B）及粪球菌属（Coprococcus）相对丰度的趋势,有利于皮肤变态反应豚鼠肠道菌群组成的恢复。

YNS益肤面霜对皮肤具有改善及修复作用,并对豚鼠肠道菌群具有一定影响。

     

妇科恶性肿瘤患者阴道微生态状况

了解妇科恶性肿瘤患者及化疗后患者阴道微生态状况, 探讨化疗后患者阴道微生态评价的临床意义。

选取2017年8月至2019年8月在我院妇科住院治疗的60例妇科恶性肿瘤患者(肿瘤组)及同期因妇科恶性肿瘤进行化疗的40例患者(化疗组)作为研究对象, 同时以40例健康体检女性作为体检组, 取阴道分泌物进行微生态评估。

肿瘤组患者阴道菌群密集度正常(++和+++)者占58.3%, 与体检组及化疗组比较差异均有统计学意义(均P < 0.05)。肿瘤组、化疗组和体检组对象中菌群正常者分别占18.3%、5.0%、55.0%, 差异均有统计学意义(均P < 0.05)。化疗组、肿瘤组和体检组菌群抑制者分别占42.5%、35.0%、10.0%, 差异均有统计学意义(均P < 0.05)。不同类型妇科恶性肿瘤患者阴道微生态状况比较差异无统计学意义(P > 0.05)。

妇科恶性肿瘤患者阴道微生态失调率增高, 化疗后患者在阴道微生态失调率升高的同时生殖道感染风险增加。

     

益生菌粉（副干酪乳酪杆菌207-27）的毒理学安全性评价

评估益生菌粉（副干酪乳酪杆菌207-27）的毒理学安全性,为其应用提供依据。

通过大鼠急性经口毒性试验、细菌回复突变试验、小鼠红细胞微核试验、小鼠精母细胞染色体畸变试验及大鼠28 d经口毒性试验研究益生菌粉（副干酪乳酪杆菌207-27）的安全性。

大鼠急性经口毒性试验结果显示,益生菌粉（副干酪乳酪杆菌 207-27）对大鼠的经口急性毒性LD₅₀均大于15.00 g/（kg•BW）,根据急性毒性分级标准属实际无毒。细菌回复突变试验、小鼠红细胞微核试验及小鼠精母细胞染色体畸变试验结果均显示阴性。大鼠28 d经口毒性试验结果表明,实验组大鼠体质量、摄食量、食物利用率、眼部状况、血液学指标、血液生化指标、脏器指数、大体及病理学检查结果与对照组相比差异均无统计学意义。

益生菌粉（副干酪乳酪杆菌207-27）具有良好的毒理学安全性。

     

羊膜腔内感染微生物分布及相关影响因素分析

研究剖宫产术中产妇的感染症状、羊水微生物分布情况及相关影响因素,为该类患者的治疗提供帮助。

采集本院2020年6月至2023年2月于剖宫产术中提取的羊水498份进行细菌培养,根据羊水微生物分布情况和相关因素,综合分析产妇临床感染症状。

498份送检羊水标本中有147份标本检出微生物,总检出率为29.5%（147/498）。498例产妇中有100例术前出现感染症状,检出微生物78株;51例术后出现感染症状,检出微生物34株;8例术后切口感染,检出微生物7株。339例没有临床感染症状的产妇检出微生物28株。羊水微生物的检出率与胎膜早破或试产后人工破膜、产妇自身阴道菌群分布、术前出现感染症状呈显著相关（均P＜0.05）。

对胎膜早破、阴道菌群失调等高危产妇及时送检标本查找病原体,对羊膜腔内感染的早期预防和针对性治疗具有显著意义。

     

CIN患者阴道微生态状况与HPV感染的关系分析

分析宫颈上皮内瘤变（CIN）患者阴道微生态与人乳头瘤病毒（HPV）感染的关系。

选取326例本院收治的CIN患者,采集阴道分泌物和宫颈脱落细胞,通过形态学和功能学检测阴道微生态状况,采用PCR-反向点杂交法进行HPV分型检测,采用二分类Logistic回归分析影响CIN患者HPV感染的因素。

CIN患者HPV阳性共256例,占78.5%,HPV阴性共70例,占21.5%。HPV阳性CIN患者白细胞计数＞10个/高倍视野、阴道清洁度Ⅲ-Ⅳ度、VVC阳性、AV阳性、BV阳性、pH值＞4.5、白细胞酯酶阳性、过氧化氢阳性占比高于HPV阴性患者,微生态正常者占比低于HPV阴性患者（P＜0.05）。二分类Logistic回归分析显示,VVC、BV、微生态正常和pH值为CIN患者HPV感染的影响因素。

CIN患者HPV感染率较高,且感染后存在阴道微生态失调,VVC、BV、微生态异常和pH值是CIN患者HPV感染的影响因素。

     

令肤适洗液皮肤和阴道局部毒性研究

目的评价令肤适皮肤和阴道局部使用的安全性。方法采用皮肤急性毒性、皮肤刺激、皮肤过敏、阴道急性毒性和阴道刺激等试验方法。结果未见令肤适具有皮肤毒性、皮肤刺激作用和明显的阴道急性毒性反应;在阴道刺激试验中低剂量未引起阴道明显的刺激反应,高剂量可引起阴道粘膜炎细胞浸润、淤血、出血及溃疡等病理变化。结论令肤适皮肤使用较安全,阴道使用浓度不宜过高。     

有抑菌能力乳杆菌的筛选及其抑菌物质的初步探究

目的 筛选具有抑菌能力的乳杆菌菌株并对其抑菌物质进行初步探究。方法 采用琼脂扩散法进行抑菌试验,筛选出具有抑菌能力的乳杆菌菌株;通过热稳定性试验检测抑菌物质耐高温的能力;通过有机酸排除与过氧化氢排除试验检测这两种物质对抑菌作用是否有影响;用胃蛋白酶、胰蛋白酶和蛋白酶K消化处理各株乳杆菌无细胞发酵液后进行抑菌试验,判断抑菌物质是否为蛋白多肽类物质。结果 2株副干酪乳杆菌与1株保加利亚乳杆菌对大肠埃希菌、铜绿假单胞菌、伤寒沙门菌和痢疾志贺菌有抑菌效果。这3株乳杆菌无细胞发酵液中的抑菌物质经过高温处理后仍具有抑菌能力,但抑菌能力与处理前相比显著降低（P＜0.05）;有机酸对照组未产生明显的抑菌圈;过氧化氢排除后的无细胞发酵液的抑菌能力未受影响;经过蛋白酶作用3株乳杆菌无细胞发酵液的抑菌能力显著降低（P＜0.05）或消失。生物被膜态副干酪乳杆菌2的抑菌能力与浮游态相近,其无细胞发酵液中的抑菌物质可以完全耐受100℃处理与胃蛋白酶的消化作用,可部分耐受胰蛋白酶的消化作用。结论 副干酪乳杆菌1、副干酪乳杆菌2和保加利亚乳杆菌具有良好的抑菌能力,它们产生的主要抑菌物质为蛋白多肽类,此物质具有较好的耐高温能力与耐蛋白酶能力;被膜态副干酪乳杆菌产生的抑菌物质表现出了更强的抗胁迫能力与稳定性。     

A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey

Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter.
Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).     

A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey.

Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter. Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).     

Effect of hydrogen peroxide on antibacterial activities of Canadian honeys

Honey is recognized as an efficacious topical antimicrobial agent in the treatment of burns and wounds. The antimicrobial activity in some honeys depends on the endogenous hydrogen peroxide content. This study was aimed to determine whether honey's hydrogen peroxide level could serve as a honey-specific, activity-associated biomarker that would allow predicting and assessing the therapeutic effects of honey. Using a broth microdilution assay, I analyzed antibacterial activities of 42 Canadian honeys against two bacterial strains: Escherichia coli (ATCC 14948) and Bacillus subtilis (ATCC 6633). The MIC90 and MIC50 were established from the dose-response relationship between antibacterial activities and honey concentrations. The impact of H2O2 on antibacterial activity was determined (i) by measuring the levels of H2O2 before and after its removal by catalase and (ii) by correlating the results with levels of antibacterial activities. Canadian honeys demonstrated moderate to high antibacterial activity against both bacterial species. Both MIC90 and MIC50 revealed that the honeys exhibited a selective growth inhibitory activity against E. coli, and this activity was strongly influenced by endogenous H2O2 concentrations. Bacillus subtilis activity was marginally significantly correlated with H2O2 content. The removal of H2O2 by catalase reduced the honeys' antibacterial activity, but the enzyme was unable to completely decompose endogenous H2O2. The 25%-30% H2O2 "leftover" was significantly correlated with the honeys' residual antibacterial activity against E. coli. These data indicate that all Canadian honeys exhibited antibacterial activity, with higher selectivity against E. coli than B. subtilis, and that these antibacterial activities were correlated with hydrogen peroxide production in honeys. Hydrogen peroxide levels in honey, therefore, is a strong predictor of the honey's antibacterial activity.     

The antibacterial activity of honey derived from Australian flora

Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57%) of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla), jarrah (Eucalyptus marginata) and jellybush (Leptospermum polygalifolium). In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8%) samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4 °C than at 25 °C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25 °C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted.     

Polyvinyl pyridine metal complex as permanent antimicrobial finishing for viscose fabric

Viscose fabrics were treated with polyvinyl pyridine (PVP) using padding technique, followed by oxidation with hydrogen peroxide or peracetic acid, which was prepared by the reaction of tetra acetyl ethylene diamine (TAED) with hydrogen peroxide. Peracetic acid gives higher oxidation of PVP than hydrogen peroxide. FTIR study proved the formation of N-oxide as a result of oxidation. Incorporation of copper and silver ion onto oxidized PVP was also proved by FTIR. The antimicrobial study emphasise that Cu/oxidized PVP and Ag/oxidized PVP have retarded the growth of bacteria significantly, and Ag/oxidized PVP has a far better biocidal activity. The antibacterial activity of both metal ions survived after washing 10 times.     

Fabrication of silver ion exchanged zeolite using scoria and its antibacterial activity

In this study, we examined the antibacterial activity of silver ion exchanged zeolite synthesized from Cheju Scoria. We synthesized zeolite in various NaOH concentrations, but zeolite synthesized in 4 M NaOH was most similar to type A zeolite. Using the synthesized zeolite, we prepared a silver ion exchanged zeolite for studies of antibacterial activity. Antibacterial tests using agar cultures of Escherichia coli (E. coli), with silver ion exchanged zeolite showed a zone of inhibition colonies bacteria did not grow near silver ion exchanged zeolite. Furthermore, spectrophotometry demonstrated a significantly low absorbance of E. coli culture mediums when silver ion exchanged zeolite was included indicating that E. coli propagation was prevented. Through results of these experiments, we conclude that synthesized products with sodalite crystal can be synthesized from Scoria, and these are suitable to produce silver ion exchanged zeolite with antibacterial activity.     

Silver nanoparticles: partial oxidation and antibacterial activities

The physical and chemical properties of silver nanoparticles that are responsible for their antimicrobial activities have been studied with spherical silver nanoparticles (average diameter approximately 9 nm) synthesized by the borohydride reduction of Ag+ ions, in relation to their sensitivity to oxidation, activities towards silver-resistant bacteria, size-dependent activities, and dispersal in electrolytic solutions. Partially (surface) oxidized silver nanoparticles have antibacterial activities, but zero-valent nanoparticles do not. The levels of chemisorbed Ag+ that form on the particle's surface, as revealed by changes in the surface plasmon resonance absorption during oxidation and reduction, correlate well with the observed antibacterial activities. Silver nanoparticles, like Ag+ in the form of AgNO3 solution, are tolerated by the bacteria strains resistant to Ag+. The antibacterial activities of silver nanoparticles are related to their size, with the smaller particles having higher activities on the basis of equivalent silver mass content. The silver nanoparticles aggregate in media with a high electrolyte content, resulting in a loss of antibacterial activities. However, complexation with albumin can stabilize the silver nanoparticles against aggregation, leading to a retention of the antibacterial activities. Taken together, the results show that the antibacterial activities of silver nanoparticles are dependent on chemisorbed Ag+, which is readily formed owing to extreme sensitivity to oxygen. The antibacterial activities of silver nanoparticles are dependent on optimally displayed oxidized surfaces, which are present in well-dispersed suspensions.     

纳米银/植物源复合抗菌剂的制备及其抑菌性能的研究

以硝酸银作为银源,水溶性淀粉作保护剂,丙酮酸钠作还原剂,氨水提供碱性环境来制备纳米银胶,并以聚乙烯吡咯烷酮(PVP)作分散稳定剂,复配红景天提取液和无患子提取液制备出纳米银/植物源复合抗菌剂。实验结果表明,纳米银胶或植物提取液仅对部分细菌或霉菌有较强抑制效果,而复合抗菌剂对细菌、霉菌均有很强抑制效果。在湿巾液中添加0.5%复合抗菌剂时,其对大肠杆菌,金黄色葡萄球菌和白色念珠菌的抗菌效率可达99%,且经过常温六个月、高温55℃一个月保存后,其抗菌活性分别可达到95%、90%左右,表明复合抗菌剂具有较强的抗菌效率及抗菌稳定性。