The potential of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hucMSC-EVs) in wound healing is promising, yet a comprehensive understanding of how fibroblasts and keratinocytes respond to this treatment remains limited. This study utilizes single-cell RNA sequencing (scRNA-seq) to investigate the impact of hucMSC-EVs on the cutaneous wound microenvironment in mice. Through rigorous single-cell analyses, we unveil the emergence of hucMSC-EV-induced hematopoietic fibroblasts and MMP13+ fibroblasts. Notably, MMP13+ fibroblasts exhibit fetal-like expressions of MMP13, MMP9, and HAS1, accompanied by heightened migrasome activity. Activation of MMP13+ fibroblasts is orchestrated by a distinctive PIEZO1-calcium-HIF1α-VEGF-MMP13 pathway, validated through murine models and dermal fibroblast assays. Organotypic culture assays further affirm that these activated fibroblasts induce keratinocyte migration via MMP13-LRP1 interactions. This study significantly contributes to our understanding of fibroblast heterogeneities as well as intercellular interactions in wound healing and identifies hucMSC-EV-induced hematopoietic fibroblasts as potential targets for reprogramming. The therapeutic targets presented by these fibroblasts offer exciting prospects for advancing wound healing strategies.
Objective To provide scientific basis for rational clinical use and traceability of outbreaks of foodborne Salmonellosis,the drug resistance and molecular typing characteristics of foodborne Salmonella in Ganzhou City was understood,and a database of drug resistance and molecular fingerprinting of foodborne Salmonella in Ganzhou City was established.Methods Serotyping,drug susceptibility testing,whole genome sequencing(WGS)and pulsed field gel electrophoresis(PFGE)were performed on 136 strains of Salmonella isolated from the active surveillance of foodborne diseases in Ganzhou City from 2020 to 2022.And drug resistance gene annotation and graphical clustering analysis were performed.Results The highest rate of foodborne Salmonella in Ganzhou City was found for STR resistance(83.09%),followed by TET(78.68%)and AMP(76.47%).Multi-drug resistant strains accounted for 76.47%,with a wide range of resistance spectrum types,and the main prevalent resistance spectrum type was AMP-TET-CHL-STR-SXT.WGS predicted a total of 61 resistance genes in 7 categories,with the highest rate of aminoglycoside resistance genes(99.19%)and the lowest rate of macrolides(8.87%).136 strains of Salmonella with S.typhimurium variant and S.typhimurium as the dominant serotype were classified into 98 band types by PFGE molecular typing.Conclusion Foodborne Salmonella in Ganzhou City has a serious drug resistance status,with a high rate of drug resistance gene carriage and diverse genotypes.The PFGE molecular type is polymorphic.The dominant serotype may cause outbreaks and epidemics,and surveillance and research should be strengthened.
目的 了解赣州市布鲁氏菌病发病趋势与特点,调查重点人群及牛、羊等动物种群布病感染情况,为赣州市布病防控策略的制定提供科学依据.方法 分析2013-2021年国家传染病报告信息管理系统布病病例资料;2015-2021年选择与牲畜及畜产品接触的相关重点职业人群100余人,2021年选择动物牛200头作为监测对象,采集静脉血3~5 mL进行检测.结果 2013-2021年赣州市布病病例报告发病数累计53例,年平均发病率为0.068 3/10万,呈逐年上升趋势,有统计学意义(x2=13.72,P<0.05);发病主要集中在春夏季,6月为发病高峰;以30~60岁年龄段为主要发病人群,占81.13%;男女性别比2.31∶1,差异有统计学意义(x2=7.571,P<0.05);职业以农民为主,占56.60%.结论 近年来赣州市布病病例报告呈逐年上升趋势,发病人群和职业结构存在差异,应针对以上特点,加强疾病监测,加大对群众尤其是重点职业人群的布病防病知识宣传、个人防护和饮食卫生等健康教育工作,强化医疗机构布病诊疗培训等.
IntroductionFull-thickness skin wound healing remains a serious undertaking for patients. While stem cell-derived exosomes have been proposed as a potential therapeutic approach, the underlying mechanism of action has yet to be fully elucidated. The current study aimed to investigate the impact of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exosomes) on the single-cell transcriptome of neutrophils and macrophages in the context of wound healing.MethodsUtilizing single-cell RNA sequencing, the transcriptomic diversity of neutrophils and macrophages was analyzed in order to predict the cellular fate of these immune cells under the influence of hucMSC-Exosomes and to identify alterations of ligand-receptor interactions that may influence the wound microenvironment. The validity of the findings obtained from this analysis was subsequently corroborated by immunofluorescence, ELISA, and qRT-PCR. Neutrophil origins were characterized based on RNA velocity profiles.ResultsThe expression of RETNLG and SLC2A3 was associated with migrating neutrophils, while BCL2A1B was linked to proliferating neutrophils. The hucMSC-Exosomes group exhibited significantly higher levels of M1 macrophages (215 vs 76, p < 0.00001), M2 macrophages (1231 vs 670, p < 0.00001), and neutrophils (930 vs 157, p < 0.00001) when compared to control group. Additionally, it was observed that hucMSC-Exosomes elicit alterations in the differentiation trajectories of macrophages towards more anti-inflammatory phenotypes, concomitant with changes in ligand-receptor interactions, thereby facilitating healing.DiscussionThis study has revealed the transcriptomic heterogeneity of neutrophils and macrophages in the context of skin wound repair following hucMSC-Exosomes interventions, providing a deeper understanding of cellular responses to hucMSC-Exosomes, a rising target of wound healing intervention.
[This corrects the article DOI: 10.3389/fimmu.2023.1142088.].
This paper studies the sexual knowledge of college students in Zhuang areas of border China, and discusses the current situation of sexual knowledge of college students in Zhuang areas. The data were collected by questionnaire and analyzed by quantitative content analysis. 525 college students in Zhuang areas were investigated. The conclusion shows that the Zhuang College Students' sexual knowledge is seriously insufficient, and the Zhuang College Students' understanding of sexual knowledge is not comprehensive. The Zhuang college students have a good grasp of the sexual knowledge of pregnancy and contraception, but they have a poor grasp of the sexual transmission route, while the Zhuang female college students have a better grasp of the sexual knowledge than the Zhuang male college students. There is no significant difference in mastering sexual knowledge between rural and urban areas, and there is no significant difference in mastering sexual knowledge between different grades. Among the 525 Zhuang college students tested, 95.05% thought they needed to understand sexual knowledge. The Zhuang college students themselves still had urgent needs. Most of the students in Zhuang universities acquire sexual knowledge through the Internet, newspapers and students, and lack formal and systematic learning opportunities. Social and cultural backgrounds shape college students' sexual knowledge. At present, there is a serious lack of sexual knowledge among college students in frontier ethnic areas. It has had a great impact on people's lives. Zhuang college students hope to learn more about sexual physiology and psychology through school lectures or compulsory courses. Gender difference is a crucial factor for the differences in sexual knowledge of Zhuang college students.
微针疗法是目前皮肤科和医疗美容领域中一种相对新颖且安全有效的微创性胶原蛋白诱导再生技术,起初由美国皮肤科医生应用于瘢痕和皱纹的治疗.微针疗法在过去数十年间发展迅速,临床上通常联合透皮给药、化学剥脱术、肉毒杆菌毒素注射、强脉冲光、激光以及射频等医美治疗技术使用.常用的微针治疗器械包括:滚轮微针、印章微针、电动微针笔和射频微针等.该文将对微针疗法的作用机制以及发展历史进行概述,旨在提供关于微针疗法科学、可靠的综合性回顾,介绍该项有效的现代皮肤美容再生性治疗技术.
随着人类预期寿命延长,对于抗衰老的需求日益增长,皮肤作为衰老的外在最直观表现受到求美者的广泛关注.Franceschi于2000年提出"炎症性衰老(inflammaging)"概念,是一种与衰老相关的慢性炎症状态;炎症性衰老是以炎性因子水平升高和细胞衰老为特征,与各种衰老相关疾病密切相关,包括皮肤炎症性衰老.该文通过总结与皮肤衰老密切相关的炎症机制,包括氧化应激、DNA损伤、微炎症理论与皮肤微生态的影响,并从炎症角度挖掘潜在治疗策略,包括干细胞、外泌体和抗氧化剂等的作用机制,以期通过靶向炎症通路为皮肤抗衰老提供新思路.
目的 研究微进化对阿萨希毛孢子菌(Trichosporon asahii,T.asahii)感染宿主情况及感染后机体免疫反应等方面的影响.方法 用微进化株(TEVO)与阿萨希毛孢子菌原代株(TO)感染Balb/c小鼠,比较两株菌感染小鼠脏器组织中真菌的相对载量、髓过氧化物酶(myeloperoxidase,MPO)、血清β-葡聚糖水平以及脾脏T细胞分化差异.结果 TEVO菌株以孢子状态为主,TO菌株以菌丝生长状态为主;TEVO组小鼠各组织相对载量、血浆(1,3)-β-D-葡聚糖水平及MPO浓度均明显低于TO组;TEVO组小鼠脾脏中CD4+T细胞和CD8+T细胞的比例均高于TO组.结论 微进化后的TEVO菌株对宿主的感染能力以及感染前期宿主对TEVO菌株的防御和杀伤能力均低于TO菌株,这可能与TEVO菌株表型变化密切相关.
Objective:To evaluate the effect of microevolution on phenotypes and drug resistance of the Trichosporon asahii biofilm. Methods:The standard strain of Trichosporon asahii was obtained from the Fungal Biodiversity Institute of the Royal Netherlands Academy of Arts and Sciences, the fluconazole-sensitive primary strain (TO) of Trichosporon asahii was isolated from a case of trichosporonosis diagnosed in the Department of Dermatology, the Seventh Medical Center of Chinese People′s Liberation Army General Hospital in 2000, and the fluconazole-resistant evolved strain (TEVO) of Trichosporon asahii was isolated from the above patient in 2014. Biofilms of the above-mentioned strains were formed in vitro, and tetrazolium salt XTT reduction assay was performed to evaluate growth kinetics of the Trichosporon asahii biofilm, and laser scanning confocal microscopy to determine the thickness of the biofilm; the sessile minimum inhibitory concentrations (SMICs) of fluconazole, itraconazole and voriconazole against the biofilms at different growth stages were determined in vitro for the evaluation of the resistance of the biofilms. One-way analysis of variance was used for comparisons among multiple groups, and Hartley test for testing homogeneity of variance. If the variance was homogeneous, least significant difference test was used for multiple comparisons; if the variance was heterogeneous, Tamhane′ T2 test was used for multiple comparisons. Results:In the adhesion (0 h) and formation stages (4- 24 hours) of the Trichosporon asahii biofilm, the metabolic activity of the evolved strain TEVO was the weakest (adhesion stage: F = 35.705, P < 0.001; formation stage: F = 15.042, P < 0.001) . At 48 hours after adhesion, the biofilms matured, and the TO strain showed the weakest metabolic activity ( F = 10.985, P < 0.001) . In the maturation stage, the biofilm thickness of the TEVO strain (26.1 ± 1.18 μm) was significantly higher than that of the TO strain (22.8 ± 1.73 μm, P = 0.001) , but significantly lower than that of the standard strain (29.5 ± 1.28 μm, P = 0.001) . As drug susceptibility testing showed, the SMICs of azole antifungal agents against the TEVO strain were higher than those against the TO strain in the adhesion and formation stages of the Trichosporon asahii biofilm, and the SMICs of azole antifungal agents against the biofilms of the 3 strains of Trichosporon asahii were all over 1 024 mg/L in the maturation stage of the biofilm. Conclusion:Under the dual pressure of host environment and antifungal drugs, adaptive changes took place in the phenotypes of the Trichosporon asahii biofilm with an increase in the resistance to azole antifungal drugs.
The opportunistic fungal pathogen Trichosporon asahii (T. asahii) is an important causal agent of mortality in immunocompromised patients and associated with frequent relapses, even with sufficient antifungal treatment. Investigating the proteomes of initial and recurrent isolates may help to identify within-host adaptive changes. In this study, using tandem mass tag (TMT)-labeling combined with liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) technology, we analyzed the proteomes of two T. asahii strains that were isolated 15 years apart from the same patient who suffered initial and recurrent episodes of systemic disseminated trichosporonosis. A total of 597 differentially expressed proteins were identified. Functional analysis showed that the increased proteins were primarily concentrated on peptide/protein/energy/drug metabolism and translation. Most of the results were determined to be consistent with the findings of phenotypic assays, such as tests for drug susceptibility, temperature growth, biofilm formation, melanization and paromomycin assays. Moreover, we performed multiple reaction monitoring (MRM) mass spectrometry to verify 27 candidate proteins, and the results of this experiment were also highly consistent with the results of the TMT analysis. Therefore, to the best of our knowledge, these data provide the first molecular evidence of how the T. asahii proteome changes related to host-specific adaptation during human infection. Significance: Systemic infection with Trichosporon asahii (T. asahii) has recently been recognized as an important causal agent of mortality in immunocompromised patients. Although triazole treatment usually works efficiently in the early phase of infection, many patients relapse. Hence, comparative analyses of the proteomics of initial and recurrent isolates may reveal evidence of adaptive changes within the host. Our study demonstrates that the recurrent strain has undergone proteomic changes using tandem mass tag (TMT)-labeling combined with liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Moreover, the results of phenotypic assays, including drug susceptibility, temperature growth, biofilm formation, melanization and paromomycin assays, were highly consistent with the proteomic changes, and multiple reaction monitoring (MRM) verification also showed similar trends to the TMT results. In summary, our study is the first to investigate the adaptation of T. asahii under pressure from antifungal chemotherapy and host immune responses.
随着社会的发展以及对于医疗美容需求的提高,越来越多的人开始关注自身的美容问题,如皱纹、黄褐斑及瘢痕等.虽然上述问题并不直接影响身体健康,但会影响个体的心理与生活质量.随着再生医学技术的不断发展,基于修复、更替或再生细胞、组织或器官结构与功能的优势,使其在医疗美容领域中具有更突出的价值.该文综述了再生医学领域中干细胞、外泌体以及富血小板血浆在医疗美容领域的临床应用进展、现存问题及展望.
目的 研究微进化对阿萨希毛孢子菌(T.asahii)与巨噬细胞RAW264.7相互作用的影响.方法 将微进化前后的T.asahii与RAW264.7细胞共培养,检测RAW264.7对两株菌的吞噬和杀伤能力以及两株菌对RAW264.7产生的细胞毒性的差异,同时分析RAW264.7自身细胞因子分泌情况的变化.结果 巨噬细胞对原代菌株(TO)的吞噬能力以及杀伤率均明显高于微进化株(TEVO);TO菌株对巨噬细胞的细胞毒性要强于TEVO;当巨噬细胞与菌株按1:3或1:6共培养24 h时,与TO共培养的巨噬细胞TNF-α和IL-6的分泌量要高于TEVO组,而按1:9共培养时TEVO组细胞因子的分泌量却高于TO组.结论 微进化后的TEVO菌株与巨噬细胞的相互作用明显弱于原代株TO,这也为TEVO菌株在宿主体内长期共存提供了良好的基础.
2019年瘙痒研究国际论坛敏感性皮肤兴趣组应用科学的统计学方法,针对敏感性皮肤的病理生理与治疗达成相关专家立场,本文对其内容进行介绍和解读.该专家立场认为敏感性皮肤不是免疫性疾病,而是与皮肤神经系统的改变有关.治疗方面,建议回避可能的诱发因素,并使用耐受性好的护肤品,特别是含有伤害感受器拮抗剂的护肤品.目前,并没有临床试验数据支持系统性或外用药物用于治疗敏感性皮肤.该专家立场建议基于影响敏感性皮肤的各种生物医学、神经和社会心理因素制定个体化的治疗方案.
Recently, biochemical and genomic studies have specified new classification methods and renamed Propionibacterium acnes as Cutibacterium acnes ( C. acnes) to better study its phylotypes and distinguish it from other Propionibacterium species . C. acnes, an important commensal bacterium in human skin, is involved in maintaining skin health, and can also turn into an opportunistic pathogen causing acne vulgaris. Latest studies have showed that the balance between different phylotypes of C. acnes and its interaction with other microorganisms play a key role in the occurrence and development of acne vulgaris. This review summarizes correlations between C. acnes phylotypes and acne vulgaris, as well as antimicrobial susceptibility and interaction with other microorganism of C. acnes.
Trichosporon asahii is the major pathogen causing invasive trichosporonosis. Conventional methods of its detection are time-consuming or costly and often require complex DNA extraction and purification steps, which hinders rapid clinical diagnosis. In this study, we evaluated colony PCR, which directly uses colonies or trace clinical samples as the template for amplification, for rapid detection of T. asahii infection. Four methods, namely, direct colony, freeze-thaw, glass beads, and enzymolysis, were compared to select the best DNA extraction strategy. We subsequently designed and screened species-specific primers targeting the intergenic spacer 1 (IGS1) of the ribosomal DNA of T. asahii and used them to detect mock infection clinical samples. The species-specific colony PCR based on glass beads proved advantageous, with short procedure time (154.8 ± 0.6 min), good sensitivity (detection limit, 102 CFU/mL), and specificity for T. asahii, indicating that this method can be used for the rapid and simple identification of clinical samples of T. asahii infection.
目的 研究阿萨希毛孢子菌(Trichosporon asahii, T.asahii)氟康唑体外诱导的耐药株与其亲本菌株的致病性差异.方法 通过最低抑菌浓度(MIC)梯度浓度升高的方法诱导出对氟康唑耐药的T. asahii环境株和临床株,T. asahii不同菌株感染BALB/c小鼠,观察不同组小鼠病死率的差异.结果 成功获得耐药表型稳定的耐药株(氟康唑MIC值>64 μg/ml),通过组织培养和活检组织病理确定建模成功.环境敏感组病死率为(57.50±3.54)%,环境耐药组病死率为(50.00±7.07)%,临床敏感组病死率为(77.50±3.54)%,临床耐药组病死率为(37.50±3.54)%.结论 环境敏感株与环境氟康唑诱导的耐药株对小鼠的致病性无明显差异,而临床来源诱导的耐药株宿主体内致病性降低,具体机制需要后续进一步研究.
目的 调查江西省赣州市恙虫病自然宿主及其体表恙螨寄生情况,为该地区恙虫病的防控提供理论依据.方法 选择赣州市于都、寻乌、赣县和上犹县作为监测点,于2015-2016年每年的9-10月利用夹夜法捕获恙螨宿主,鉴定分类并梳检其体表恙螨,对恙螨种类进行鉴定并计算恙螨指数.结果 共捕获小兽429只,捕获率为8.95%,捕获动物共7种,其中以黄毛鼠为优势鼠种,占捕获总数的51.75%;带螨宿主动物188只,以黄毛鼠居多,总带恙螨率为43.82%,黑线姬鼠、褐家鼠和黄毛鼠带恙螨率较高;共捕获恙螨2 875只,带恙螨指数为6.70,其中褐家鼠、黑线姬鼠和黄毛鼠带恙螨指数较高;对188只宿主动物寄生恙螨进行鉴定,结果显示恙螨共5种,以地里纤恙螨为优势种,占61.70%.结论 赣州市可能是以黄毛鼠为优势宿主动物、地里纤恙螨为优势传播媒介的恙虫病自然疫源地,应开展恙虫病的病原学和人群流行病学研究,为该病的防治提供进一步的证据.
目的 利用模型评估气温对流感发病的影响,为流感发病的预警预测提供依据. 方法 收集2014-2016年赣州市流感日发病资料和同期气温资料,采用分布滞后非线性模型(distributed lag non-linear model,DLNM)分析气温与流感发病的关系. 结果 流感日发病人数与日平均气温、日最高气温、日温差呈负相关(均P<0.05),与日最低气温无关(P>0.05).流感发病随日平均气温变化而变化,呈非线性关系,25℃为最适温度.当日平均温度<16.00℃,当天流感发病风险明显上升(RR>1,95% CI>1).当日平均温度<25.00℃,滞后1d的流感发病风险明显上升(RR>I,95%CI>1).结论 气温与流感发病明显相关,但滞后效应较弱.
目的 观察调节性T细胞(regulatory T cells,Tregs)在播散性阿萨希毛孢子菌(Trichosporon asahii,T.asahii)病小鼠模型中的表达,初步探讨Foxp3+调节性T细胞在播散性毛孢子菌病发病机制中可能发挥的作用.方法 50只雄性BALB/c小鼠随机分为试验组和对照组,每组25只,分别于尾静脉接种阿萨希毛孢子菌悬液和生理盐水.接种后第3,7,14,21及28天,流式细胞仪检测两组小鼠脾脏单个核细胞悬液中CD4+CD25+Foxp3+调节性T细胞比率;实时荧光定量聚合酶链反应(PCR)检测两组小鼠脾脏Foxp3 mRNA水平表达情况.结果 试验组小鼠脾脏中CD4+CD25+Foxp3+调节性T细胞比率及Foxp3 mRNA表达随着感染进程先增高后下降至正常水平.接种后第3、28天,试验组小鼠脾脏单个核细胞中CD4+CD25+Foxp3+调节性T细胞的比例与对照组差异无统计学意义(P>0.05);接种后第7、14及21天调节性T细胞的比例较对照组明显上升,差异有统计学意义(P<0.05).接种后第3、28天,试验组小鼠脾脏Foxp3 mRNA表达水平与正常对照组相比,差异无统计学意义(P>0.05);接种后第7、14、21天与对照组相比,差异有统计学意义(P<0.05).结论 阿萨希毛孢子菌可以诱导小鼠体内CD4+CD25+Foxp3+调节性T细胞在感染中后期表达增高,调节性T细胞可能参与调节播散性毛孢子菌病的免疫应答.