Penetration

渗透
  • 文章类型: Journal Article
    细菌性皮肤和软组织感染(STTI)是广泛的微生物入侵皮肤和深层组织。当治疗SSTI时,局部药物递送系统是最有利的施用途径。这取决于他们诱发系统性不良事件的最小风险,减少细菌耐药性的发展,和易于应用。然而,它们有几个缺点,包括缺乏对药物释放曲线的控制,皮肤过敏,以及某些化合物通过皮肤的有限渗透性。为了解决这些限制,开发了几种纳米载体系统,纳米脂质体是SSTI局部治疗的主要递送系统。尽管在过去十年中对脂质体进行了大量研究,关于专门为SSTI设计这些载体的详细知识仍然存在差距。因此,迫切需要进行全面的研究,重点是将纳米脂质体用于SSTI,并提供对SSTI和脂质体制剂的广泛了解。这篇综述探讨了细菌SSTI,涵盖他们的流行病学,分类,微生物学,和管理。它强调了基于脂质体的纳米囊泡在增强抗生素和天然抗菌化合物用于SSTI管理的局部施用方面的贡献。它还深入研究了脂质体制剂变化对疾病治疗结果的影响。此外,它为使脂质体的特性与感染类型保持一致提供了指导,深度,属性,和病原体。这标志着药物设计领域的实质性飞跃,发展,和交付。
    Bacterial skin and soft tissue infections (SSTIs) are widespread microbic invasions of the skin and deeper tissues. Topical drug delivery systems are the most favored administration pathway when treating SSTIs. This is down to their minimal risk of inducing systemic adverse events, reduced development of bacterial resistance, and ease of application. However, they have several drawbacks, including the lack of control over the drug release profile, skin irritations, and the limited permeability of certain compounds through the skin. To address these limitations, several nanocarrier systems were developed, with nanoliposomes standing out as the leading delivery system for the topical management of SSTIs. Despite considerable research into liposomes over the past decade, there remains a gap in detailed knowledge about designing these carriers specifically for SSTIs. Consequently, there is a pressing need for comprehensive research that focuses on the use of nanoliposomes for SSTIs and offers an extensive understanding of both SSTIs and liposomal formulations. This review explores bacterial SSTIs, covering their epidemiology, classification, microbiology, and management. It emphasizes the contribution of liposome-based nanovesicles in enhancing the local administration of antibiotics and natural antibacterial compounds for SSTI management. It also delves into the effects of liposomal formulation changes on the disease therapeutic outcomes. Additionally, it provides a guide for aligning the characteristics of the liposomes with the infection types, depths, properties, and causative agents. This signifies a substantial leap forward in the domains of drug design, development, and delivery.
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  • 文章类型: Case Reports
    背景:鱼骨从胃进入脾脏,导致脾脓肿,是极其罕见的情况。
    方法:我们报告一例鱼骨从胃侵入脾脏,表现为脾脓肿和急性腹膜炎,术前通过腹部对比增强CT扫描诊断,随后通过保脾手术治疗。
    结论:鱼骨从胃进入脾脏,导致脾脓肿,这是极为罕见的。我们通过保脾手术成功诊断和治疗了这个病例,病人恢复得很好。
    结论:一例罕见的鱼骨从胃侵入脾脏导致脾脓肿的病例在术前通过放射学诊断,并通过保脾手术治疗。
    BACKGROUND: Fishbone penetrating from the stomach into the spleen, causing a splenic abscess, is an extremely rare condition.
    METHODS: We report a case of fishbone penetration from the stomach into the spleen, presenting as a splenic abscess and acute peritonitis, diagnosed pre-operatively with a contrast-enhanced CT scan of the abdomen and subsequently managed with spleen-preserving surgery.
    CONCLUSIONS: Fishbone penetration from the stomach into the spleen, causing a splenic abscess, which is an extremely rare occurrence. We successfully diagnosed and managed this case with spleen-preserving surgery, and the patient recovered well.
    CONCLUSIONS: A rare case of fishbone penetration from the stomach into the spleen causing a splenic abscess was diagnosed radiologically pre-operatively and managed by a spleen-preserving procedure.
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  • 文章类型: Case Reports
    背景:由于其能够提供稳定的固定并允许早期动员的能力,掌侧钢板已成为桡骨远端骨折手术稳定的推荐技术。由于未检测到的螺钉穿刺或钻孔插入,长伸肌(EPL)肌腱可能会受伤或破裂。手术期间,它是至关重要的检测任何潜在的螺旋渗透,以便它可以被纠正。
    方法:一名32岁的女性在桡骨远端钢板术后6周表现为无法伸出左手拇指。临床检查显示指间关节伸展丧失,僵硬的手腕,手腕背侧的压痛点,和完整的感觉神经功能。
    结论:动态超声和磁共振成像(MRI)均未发现肌腱断裂或EPL肌腱运动的证据。X射线显示远端骨phy螺钉穿透了远皮质。术中,发现EPL肌腱被螺钉撞击。肌腱被释放,进行了肌腱溶解,远端螺钉缩短。
    结论:为了评估螺钉向远皮质的渗透,桡骨远端骨折的掌侧钢板应使用术中成像视图进行,例如外侧,45度仰卧起坐,45度内旋,背侧相切,和天际线视图。桡骨远端骨折固定术后及时干预保留肌腱功能,早期发现肌腱受损对防止额外损伤至关重要。
    BACKGROUND: Due to its ability to provide stable fixation and permit early mobilization, volar plating has become the recommended technique for the surgical stabilization of distal radius fractures. The extensor pollicis longus (EPL) tendon may be injured or ruptured as a result of undetected screw penetration or drill plunging. During surgery, it is critical to detect any potential screw penetration so that it can be corrected.
    METHODS: A 32-year-old woman presented six weeks post-distal radius plating with an inability to extend her left thumb. Clinical examination revealed loss of extension at the interphalangeal joint, stiff wrist, tender point over the dorsal aspect of the wrist, and an intact sensory nerve function.
    CONCLUSIONS: Dynamic ultrasound and magnetic resonance imaging (MRI) both revealed no evidence of tendon rupture or EPL tendon movement. X-rays revealed the distal epiphyseal screws penetrating the far cortex. Intraoperatively, the EPL tendon was found to be impinged by a screw. The tendon was released, tenolysis was performed, and the distal screws were shortened.
    CONCLUSIONS: In order to assess screw penetration into the far cortex, volar plating for distal radius fractures should be performed using intraoperative imaging views such as lateral, 45-degree supination, 45-degree pronation, dorsal tangential, and skyline views. Timely interventions after distal radius fracture fixation preserve tendon function, and early detection of tendon compromise is essential to preventing additional damage.
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  • 文章类型: Journal Article
    化学战剂(CWA)作为气态物质和液态气溶胶构成威胁,士兵需要化学战防护服。最重要的考虑因素在于服装作为相关CWA的屏障的有效性。本文提出了一种动态样本测试方法,旨在评估此类衣服对液相气溶胶渗透的性能。该方法的核心是一个专门的测试单元,旨在向左和向右旋转,集成在实验室风洞中,以不同的风速复制与任务相关的条件。利用癸二酸二(2-乙基己基)酯颗粒作为液体气溶胶,测试在1.0、3.0和5.0m/s的风速下进行。渗透评估依赖于分析织物下游和上游的颗粒计数,初步研究表明,在等效面速度为5.0cm/s时,较高的风速和织物的透气性会增加穿透力。有趣的是,当织物样品进行旋转时,渗透率降低。设计的系统和方法证明了一致和可重复的结果,为优化化学战防护服的有效性提供有价值的见解。这项研究有助于推进防护服的测试方法,对于确保军事人员在危险环境中的安全至关重要。
    Chemical warfare agents (CWAs) pose a threat as gaseous substances and as liquid aerosols, necessitating chemical warfare-protective clothing for soldiers. The paramount consideration lies in the effectiveness of the clothing as a barrier against the pertinent CWAs. This paper presents a dynamic swatch test method aimed at evaluating the performance of such clothing against liquid-phase aerosol penetration. Central to the methodology is a specialized test cell designed to rotate to the left and right, integrated within a laboratory wind tunnel, replicating mission-relevant conditions with varying wind speeds. Utilizing di(2-ethylhexyl) sebacate particles as liquid aerosols, tests were conducted at wind speeds of 1.0, 3.0, and 5.0 m/s. Penetration assessment relied on analyzing particle counts downstream and upstream of the fabric, with preliminary studies showing that higher wind speeds and fabric air permeabilities increase penetration at an equivalent face velocity of 5.0 cm/s. Interestingly, penetration decreased when fabric samples were subjected to rotation. The system and methodology devised demonstrated consistent and repeatable results, offering valuable insights into optimizing the effectiveness of chemical warfare-protective clothing. This research contributes to advancing methodologies for testing protective clothing, crucial for ensuring the safety of military personnel in hazardous environments.
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  • 文章类型: Journal Article
    聚合物介导的药物/基因递送的表面官能化对疾病治疗具有巨大的潜力。然而,聚合物表面官能化的设计原理仍然难以捉摸。在这项研究中,我们采用计算机模拟来演示刚度,长度,密度,和聚合物配体的分布影响它们穿过细胞膜的渗透能力。我们的模拟表明,聚合物配体的刚度影响它们跨膜运输货物的能力。增加聚合物配体的刚度可以促进它们跨膜的递送,特别是对于较大的货物。此外,适当增加聚合物配体的长度可以更有利于协助货物进入膜的下层。此外,聚合物配体在货物表面的分布在其运输中也起着至关重要的作用。具体来说,聚合物配体的四分之一模式和条纹模式分布表现出更高的渗透能力,协助货物穿透膜。这些发现为设计用于药物/基因递送的高效功能化聚合物配体提供了仿生灵感。
    The surface functionalization of polymer-mediated drug/gene delivery holds immense potential for disease therapy. However, the design principles underlying the surface functionalization of polymers remain elusive. In this study, we employed computer simulations to demonstrate how the stiffness, length, density, and distribution of polymer ligands influence their penetration ability across the cell membrane. Our simulations revealed that the stiffness of polymer ligands affects their ability to transport cargo across the membrane. Increasing the stiffness of polymer ligands can promote their delivery across the membrane, particularly for larger cargoes. Furthermore, appropriately increasing the length of polymer ligands can be more conducive to assisting cargo to enter the lower layer of the membrane. Additionally, the distribution of polymer ligands on the surface of the cargo also plays a crucial role in its transport. Specifically, the one-fourth mode and stripy mode distributions of polymer ligands exhibited higher penetration ability, assisting cargoes in penetrating the membrane. These findings provide biomimetic inspiration for designing high-efficiency functionalization polymer ligands for drug/gene delivery.
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  • 文章类型: Journal Article
    为了解决普遍存在的染料木素(GST)代谢和肠道吸收不足,设计了一种口服长效和胃原位胶凝凝胶,用于包封和定位负载的染料木黄酮-人参(GST-GNS)固体分散体的肠道释放。由于口服吸收时GST的高乳房灌注,开发GST-GNS固体分散体可增强GST的溶解和渗透,同时对乳腺癌(BC)具有协同作用。GST-GNS固体分散体的生理化学分析,发布分析,凝胶表征,储存稳定性,穿透力,并进行了体外细胞毒性研究。与原始GST相比,GST-GNS固体分散体显示出改善的溶解和渗透。通过扫描电子显微镜和傅里叶变换-红外分析揭示了GST-GNS固体分散体均一形状颗粒和亲水接触,分别。GST-GNS固体分散体的衍射图显示无定形特征。第二种改进涉及产生装载有GST-GNS固体分散体的胃原位胶凝系统。该系统证明了使用固体分散体改善的GST渗透,以及GST在肠道介质中的局部释放和针对BC的抗肿瘤协同作用。为了更好的治疗BC,建议使用包含GST-GNS固体分散体的创新口服GST长效凝胶。
    To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST\'s dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion\'s diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended.
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  • 文章类型: Journal Article
    低水平激光治疗(LLLT)通过减少口腔内的疼痛和炎症,已显示出作为猫科动物慢性牙龈炎的替代疗法的益处。与口内应用相比,猫的口外应用技术提供了更多的舒适度。然而,LLLT通过颊组织的疗效仍存在争议。本研究旨在研究使用具有各种设置和不同应用技术的830nm连续波的LLLT的穿透功效。
    本研究包括24只健康猫。通过口外应用,LLLT的波长为830nm,输出功率为200mW,在连续波模式下使用2和6J/cm2的通量。本研究比较了不同的距离(接触和非接触)和三种不同的传输介质(无介质,酒精,和生理盐水溶液)。口腔内激光功率的测量表示为平均输出功率(MOP)。
    所有注量的渗透功效均可检测到,距离,和传输介质,平均颊厚度为2.68毫米。MOP在2和6J/cm2的注量之间没有差异(p=0.19)。在没有媒体的情况下,与酒精相比,MOP显着较高(p<0.05),但与生理盐水溶液没有显着差异(p=0.26)。
    LLLT的口外应用证明了通过接触和非接触皮肤(<10mm)的颊组织的渗透功效。这是临床实践中口腔疾病的潜在替代疗法。然而,在临床实践中需要进一步研究治疗的疗效。
    UNASSIGNED: Low-level laser therapy (LLLT) has shown benefits as an alternative treatment of feline chronic gingivostomatitis by reducing pain and inflammation within the oral cavity. Extraoral application technique in cats provides more comfort compared to intraoral application. However, the efficacy of LLLT through buccal tissue is still controversial. This study aimed to investigate the penetration efficacy of LLLT using 830 nm continuous waves with various settings and different application techniques.
    UNASSIGNED: Twenty-four healthy cats were included in this study. The wavelength of LLLT was 830 nm with an output power of 200 mW through extraoral application, using fluences of 2 and 6 J/cm2 in continuous-wave mode. This study compared different distances (contact and non-contact) and three different transmission media (absent media, alcohol, and normal saline solution). Measurement of the laser power within the oral cavity is represented as the mean output power (MOP).
    UNASSIGNED: Penetration efficacy was detectable for all fluences, distances, and transmission media, with an average buccal thickness of 2.68 mm. MOP did not differ between fluences of 2 and 6 J/cm2 (p = 0.19). In the absence of media, MOP was significantly higher compared with alcohol (p < 0.05) but was not significantly different from normal saline solution (p = 0.26).
    UNASSIGNED: Extraoral application of LLLT demonstrated penetration efficacy through the buccal tissue with both contact and non-contact skin (<10 mm). This is a potential alternative treatment for oral diseases in clinical practice. However, there is a need for further study on the efficacy of treatment in clinical practice.
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  • 文章类型: Journal Article
    背景:中枢神经系统(CNS)区室化为HIV持续存在和耐药性发展提供了机会。很好地描述了脑脊液(CSF)和脑物质之间关于HIV持久性的差异。然而,CSF通常用作CNS药物暴露的替代品,来自固体脑组织的知识很少见。
    方法:Dolutegravir,替诺福韦,在49名乌干达死者的尸检过程中收集的13个CNS区域以及血浆中测量了拉米夫定和依法韦仑的浓度。从死亡到尸检的中位时间为8(IQR5,15)小时。为了评估死后的再分配,在小鼠模型中进行了时程研究.
    结果:穿透率最高的区域是脉络丛/蛛网膜(dolutegravir和替诺福韦),CSF(拉米夫定),和颈脊髓/脑膜(依法韦仑);最低的是call体(dolutegravir和替诺福韦),额叶(拉米夫定),和顶叶(efavirenz)。平均而言,大脑浓度为84%,87%,76%的脑脊液用于dolutegravir,替诺福韦,分别为拉米夫定。在小鼠模型中观察到死后再分布,替诺福韦和拉米夫定浓度增加350%,依法韦仑浓度在死后24小时下降24%。
    结论:死后组织分析为研究CNS抗逆转录病毒渗透提供了一个独特的机会。观察到区域差异为识别病毒区室化和/或神经毒性的机制铺平了道路。
    BACKGROUND: Central nervous system (CNS) compartmentalization provides opportunity for HIV persistence and resistance development. Differences between cerebrospinal fluid (CSF) and cerebral matter regarding HIV persistence are well described. However, CSF is often used as surrogate for CNS drug exposure, and knowledge from solid brain tissue is rare.
    METHODS: Dolutegravir, tenofovir, lamivudine and efavirenz concentrations were measured across 13 CNS regions plus plasma in samples collected during autopsy in 49 Ugandan decedents. Median time from death to autopsy was 8 (IQR 5,15) hours. To evaluate postmortem redistribution, a time course study was performed in a mouse model.
    RESULTS: Regions with the highest penetration ratios were choroid plexus/arachnoid (dolutegravir and tenofovir), CSF (lamivudine), and cervical spinal cord/meninges (efavirenz); the lowest were corpus callosum (dolutegravir and tenofovir), frontal lobe (lamivudine), and parietal lobe (efavirenz). On average, brain concentrations were 84%, 87%, and 76% of CSF for dolutegravir, tenofovir, and lamivudine respectively. Postmortem redistribution was observed in the mouse model, with tenofovir and lamivudine concentration increased by 350% and efavirenz concentration decreased by 24% at 24-hours post-mortem.
    CONCLUSIONS: Analysis of postmortem tissue provides a unique opportunity to investigate CNS antiretroviral penetration. Regional differences were observed paving the way to identify mechanisms of viral compartmentalization and/or neurotoxicity.
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  • 文章类型: Journal Article
    角质病,由病原真菌引起,是一种棘手的致盲眼病.角膜渗透是常规抗真菌药物治疗角膜真菌病的基本要求。由于角膜独特的解剖和生理结构,渗透能力不足阻碍了治疗功效。尽管出现了多种抗真菌药物递送系统和先进的抗真菌纳米材料,在过去的十年中,实现角膜渗透仍然具有挑战性。在研究中,我们制造了一种渗透性离子有机分子笼型纳米酶(OMCzyme),用于治疗角膜真菌病。OMCzyme的合成包括两个步骤。最初,通过三甲酰基间苯三酚和2,3-二氨基丙酸的[23]环亚胺化反应合成了离子型OMC。随后,OMCzyme是通过在有机笼中Fe2+与羧基阴离子和酚羟基配位而制造的,进一步在OMC-Fe配合物表面沉积银纳米粒子。所制备的OMCzyme表现出优异的水分散性,过氧化物酶样活性,体外和体内生物相容性,和角膜渗透。值得注意的是,纳米酶显示了靶向抗真菌活性,有效对抗镰刀菌对人角膜上皮细胞的细胞毒性可忽略不计。混合模拟物进一步证明可有效治疗小鼠的角膜真菌病,表明OMCzyme治疗真菌传染病的潜力。本文受版权保护。保留所有权利。
    Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe2⁺ with carboxyl anions and phenolic hydroxyls in the organic cage, and further deposition of silver nanoparticles on the surface of OMC-Fe complex. The as-prepared OMCzyme demonstrates excellent water dispersion, peroxidase-like activity, in vitro and in vivo biocompatibility, and corneal penetration. Notably, the nanozyme displays targeted antifungal activity, effectively combating Fusarium solani with negligible cytotoxicity toward human corneal epithelial cells. The hybrid mimic is further demonstrated to be effective in treating keratomycosis in mice, indicating the potential of OMCzyme for curing fungal infectious diseases.
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  • 文章类型: Journal Article
    痤疮杆菌是一种机会病原体,被认为是寻常痤疮的促成因素。角质蛋白和皮脂塞在毛囊中的积累促进痤疮杆菌的增殖,导致炎性痤疮。尽管有许多用于痤疮皮肤的抗菌化妆品可用,它们的功效通常针对痤疮梭菌的浮游细胞进行评估。有限的研究已经评估了对角蛋白和皮脂塞内的微生物的抗微生物作用。这项研究调查了抗菌爽肤水是否可以渗透角蛋白和皮脂塞,对痤疮杆菌表现出杀菌作用。对角蛋白和皮脂塞的扫描电子显微镜和下一代测序分析表明,痤疮丙酸杆菌在塞内增殖,主要呈生物膜状形态。为了阐明抗菌爽肤水对角蛋白和皮脂塞内的C.acnes的潜在杀菌作用,我们将插头浸入碳粉中,用LIVE/DEADBacLight细菌活力试剂盒对它们进行染色,以可视化微生物活力,用共焦激光扫描显微镜观察。结果表明,塞中的大多数微生物被抗菌调色剂杀死。为了定量评估调色剂对角蛋白和皮脂内的C.acnes的杀菌效力,我们用接种的痤疮梭菌型菌株和从痤疮易发皮肤收集的分离物浸入调色剂中并获得活细胞计数。人工塞内的类型菌株和隔离物的数量减少了2.2log和1.2log以上,分别,表明抗菌调色剂通过角蛋白和皮脂塞渗透对痤疮梭菌表现出杀菌作用。
    Cutibacterium acnes is an opportunistic pathogen recognized as a contributing factor to acne vulgaris. The accumulation of keratin and sebum plugs in hair follicles facilitates C. acnes proliferation, leading to inflammatory acne. Although numerous antimicrobial cosmetic products for acne-prone skin are available, their efficacy is commonly evaluated against planktonic cells of C. acnes. Limited research has assessed the antimicrobial effects on microorganisms within keratin and sebum plugs. This study investigates whether an antibacterial toner can penetrate keratin and sebum plugs, exhibiting bactericidal effects against C. acnes. Scanning electron microscopy and next-generation sequencing analysis of the keratin and sebum plug suggest that C. acnes proliferate within the plug, predominantly in a biofilm-like morphology. To clarify the potential bactericidal effect of the antibacterial toner against C. acnes inside keratin and sebum plugs, we immersed the plugs in the toner, stained them with LIVE/DEAD BacLight Bacterial Viability Kit to visualize microorganism viability, and observed them using confocal laser scanning microscopy. Results indicate that most microorganisms in the plugs were killed by the antibacterial toner. To quantitatively evaluate the bactericidal efficacy of the toner against C. acnes within keratin and sebum, we immersed an artificial plug with inoculated C. acnes type strain and an isolate collected from acne-prone skin into the toner and obtained viable cell counts. The number of the type strain and the isolate inside the artificial plug decreased by over 2.2 log and 1.2 log, respectively, showing that the antibacterial toner exhibits bactericidal effects against C. acnes via keratin and sebum plug penetration.
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