生物活性玻璃(Bioactive glasses,BGs)已经在再生医学和组织工程领域有了广泛应用,其与体液接触可产生碳酸羟基磷灰石,从而与骨组织紧密结合,所以常用于骨缺损或牙齿的替代、再生及修复.随着技术与材料的逐渐发展,越来越多的证据证明了BGs在软组织修复中的发展潜力.BGs具备一定的抗菌作用,这种特性在组织修复中的优势明显,通过改变其组分,或与不同材料(如功能性离子、聚合物、生物因子等)结合,能更快速有效地促进伤口愈合.本文回顾了BGs的发展进程,并通过伤口修复机制探讨BGs加速伤口修复的可能机制,最后对BGs在伤口修复中的研究发展趋势进行解读.
Purpose:Soft tissue filler injection is less invasive than surgical approaches for facial aesthetic improvement. This study evaluated the safety and effectiveness of the soft tissue filler VYC-20L (Juvéderm Voluma® XC) for improvement of volume and aesthetic appearance of the nose in Chinese subjects. Patients and Methods:In a prospective, multicenter, no-treatment-controlled study in China, adult subjects were randomized 3:1 to receive VYC-20L (treatment group) or have optional treatment delayed by 24 weeks (control group). The treatment group received VYC-20L on day 1 plus optional touch-up at week 8 for suboptimal improvement. The primary effectiveness measure was mean change in nose area volume from baseline to week 24 by digital analysis of three-dimensional (3D) images. Multiple secondary effectiveness and safety measures were assessed. Results:Of 164 subjects randomized, 162 were treated, and 157 comprised the modified intent-to-treat population (mean age, 31 years; 94% female). In the treatment group, mean VYC-20L volume injected was 1.18 mL (initial treatment) and 0.67 mL (touch-up; n = 46 [38.3%]). VYC-20L achieved significantly larger changes in nose area volume than control at week 24 (2.032 vs ‒0.005 cm3, respectively; p < 0.0001) and greater improvements on the Global Aesthetic Improvement Scale (investigator and subject), Nose Satisfaction Scale, and other 3D measures. No treatment-related adverse events occurred. Most injection site responses were mild/moderate, resolving within 14 days. Mean initial/touch-up treatment procedural pain ratings were less than 3 (0‒10 scale; higher = worse pain). Conclusion:VYC-20L is safe and effective for nose augmentation in Chinese adults.
Negative-pressure wound therapy is widely used in burn populations. Traditionally, negative-pressure devices use persistent vacuum suction, requiring a longer hospital stay. In this study, we applied a novel negative-pressure wound dressing for burn wounds, which eliminates the hospital stay. The medical records of 39 patients with partial-/full-thickness burns treated by negative-pressure wound dressing were retrospectively analyzed. The average burn area, burn degree, healing duration, cost, and incidents during treatment were determined and compared with previous data for conventional therapies. In conclusion, for patients diagnosed with partial-thickness or full-thickness burns and a burn area <34.6 ± 2.21 cm2, the negative-pressure wound dressing is a reliable option, especially for burnt children. Moreover, the negative-pressure wound dressing treatment was not only much cheaper than conventional therapies, but also eliminated hospital stay in patients with small-area deep burn wounds.
Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-β pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-β, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-β pathways in macrophages.
Transforming growth factor-beta 1 (TGF-beta 1) signaling pathway has been implicated in the fibroblast activation of hypertrophic scarring (HS). Previously, we proposed a new biotherapeutic strategy to combat HS by disrupting the intermolecular interaction of TGF-beta 1 with its cognate type-II receptor (T beta R-II). Here, we further demonstrate that the binding site of TGF-beta 1 to T beta R-II is not overlapped with the conformational wrist epitope and linear knuckle epitope that are traditionally recognized as the functional binding sites of bone morphogenetic protein-2 (BMP-2) to its type-II receptor (BMPR-II), which can thus be regarded as a new functional site we called elbow epitope. Structural, energetic, and dynamic investigations reveal that the elbow epitope consists of two sequentially discontinuous, spatially vicinal segments Loop(30-34) and Turn(90-95); they cannot work effectively to independently interact with T beta R-II. Rational redesign of the epitope is performed using an integrated in silio-in vitro method based on crystal and modeled structure data. In the procedure, the two epitope segments are split from the interface of TGF-beta 1-T beta R-II complex and then connected with each other in a head-to-tail manner by adding a flexible poly-(Gly)n linker between them, thus resulting in a series of combined peptides. We found that the peptide affinity reaches maximum at n = 2, which shares a consistent binding mode with the elbow epitope at native complex interface. The linker of either too long (n > 2) or too short (n < 2) cannot properly place the gap space between the two segments, thus impairing the binding compatibility of designed peptides with T beta R-II active site.
目的 探索TBC1D3基因对增生性瘢痕形成的影响及作用机制.方法 分别在TBC1D3转基因小鼠和对照组小鼠背部制备增生性瘢痕模型;应用RT-PCR技术分别在术前、术后2周、术后4周时,检测转基因小鼠与对照组小鼠TBC1D3基因表达水平;分别于术后2周、4周时收集各组瘢痕标本,采用Masson染色观察瘢痕组织病理学改变并评分;流式细胞仪检测术后2周、4周时转基因小鼠与对照组小鼠外周血巨噬细胞表型.结果 术前、术后转基因小鼠中TBC1D3基因均明显表达,而对照组未见表达.术后2周、4周,转基因小鼠的瘢痕组织病理学评分均较对照组显著降低(P<0.05);术后2周、4周,转基因小鼠外周血中M1型巨噬细胞比例较对照组小鼠均显著降低(P<0.05).结论 TBC1D3基因可以有效抑制增生性瘢痕形成,其机制可能是通过抑制M1型巨噬细胞极化实现的.
目的:探讨支架血管成形术治疗颈内动脉次全闭塞型脑梗死亚急性期患者的效果.方法:选取2017年9月-2019年10月本院收治的60例颈内动脉次全闭塞型脑梗死亚急性期患者的临床资料进行回顾性分析.按治疗方法不同分为单纯药物组与介入治疗组,每组30例.单纯药物组给予常规用药治疗,介入治疗组行颈动脉支架血管成形术治疗.比较两组血管狭窄程度、血管再通率、治疗后1年血管再狭窄率、美国国立卫生研究院脑卒中量表(NIHSS)、改良Rankin量表(mRS)评分、并发症发生与预后情况.结果:治疗后,介入治疗组血管狭窄程度与血管再通率均优于单纯药物组(P<0.05).介入治疗组治疗后1年血管再狭窄率低于单纯药物组(P<0.05).介入治疗组并发症发生率低于单纯药物组,且预后良好率高于单纯药物组(P<0.05).治疗后6个月,介入治疗组NIHSS与mRS评分均低于单纯药物组(P<0.05).结论:支架血管成形术治疗颈内动脉次全闭塞型脑梗死亚急性期患者可提高血管再通率,可有效改善病变血管狭窄程度,改善预后,安全性好.
目的 探究桃叶珊瑚苷对机械张力诱导的增生性瘢痕的抑制作用.方法 建立张力诱导增生性瘢痕小鼠模型,腹腔注射桃叶珊瑚苷,2周、4周后取材,HE染色观察其组织学改变并评分,Western-blot检测相关炎症蛋白以及信号通路分子的表达.结果 注射桃叶珊瑚苷小鼠的瘢痕评分较对照组显著降低,且其MCP-1、TNF-α、p-PI3K/p-Akt信号通路表达水平较注射前显著降低,而对照组无明显变化.结论 桃叶珊瑚苷在动物体内可以通过减轻炎症反应有效抑制增生性瘢痕形成,该作用可能是通过抑制PI3K/Akt信号通路介导的.
1临床资料 患者,男性,52岁,因“头痛2个月余口角歪斜3d”于2018年1月12日入住本院神经内科四病区.患者2个月前无明显诱因反复出现左颞侧、外耳道阵发性针刺样疼痛,间隔时间短暂,1个月后疼痛部位扩展至右侧,疼痛无明显加重及缓解因素,无发热、头晕及恶心、呕吐,无牙龈、皮肤出血及黑便,无胸痛、发热、抽搐、复视及视物模糊,无肢体乏力、麻木及意识改变,先后就诊于本院门诊及长沙市多家三甲医院,考虑为“疱疹病毒感染后神经痛”等,使用“阿昔洛韦、磷甲酸钠”抗病毒,“加巴喷丁”止痛等药物治疗,症状无明显缓解并渐渐加重.
The healing of acute wounds is vital to humans and is a well-orchestrated process that involves systemic and local factors. However, there is a lack of effective and safe clinical therapies. The collagen triple helix repeat containing 1 (CTHRC1) protein is a type of exocrine protein that has been recently reported to contribute to tissue repair. Our aim is to validate the promoting effects of CTHRC1 on the healing of acute wounds and to elucidate the underlying molecular mechanism. Therefore, we first established acute wound healing mouse models and confirmed that CTHRC1 accelerates the healing process of acute wounds. Then, we characterized wound macrophages using a polyvinylalcohol (PVA) sponge model and used Western blotting to investigate the molecular mechanism. We found that CTHRC1 increased the M2 macrophage population and the TGF-β expression level as a result of the activation of the TGF-β and Notch pathways, which eventually contributed to the promotion of wound healing. Inhibition of the Notch pathway showed attenuated M2 macrophage recruitment, and it decreased the TGF-β expression level. These results substantiate our hypothesis that CTHRC1 promotes wound healing by recruiting M2 macrophages and regulating the TGF-β and Notch pathways.
增生性瘢痕是一种以胶原过度沉积为特征的组织纤维化疾病,其形成机制涉及多种细胞及细胞因子的调控.近年来发现,M1/M2巨噬细胞的极化反应与器官纤维化进展有关.现对巨噬细胞在增生性瘢痕形成机制中的抗纤维化作用及其相关机制的潜在治疗价值作一综述.
为降低区域性脑卒中患者的发病率,提高及时就诊率以降低致残率与死亡率,通过在区域内开展脑卒中高危人群的筛查、登记、干预、复查及访视,实施科学管理、流程布置,实现社区医院和专科医院医连体的构建,探索并形成脑卒中一体化的防治构建模式.针对区域性脑卒中综合性防治体系构建存在的一些问题进行分析,探索改进的对策,实现了脑卒中预防救治质量的持续改进.
脂肪是体现人体形态美的重要物质.以往人们对形态美的认识主要集中于体态匀称、不臃肿,因此自20世纪70年代脂肪抽吸术诞生起,该手术一直是深受欢迎的形体雕塑手段之一. 然而,随着人们生活水平的提高,对形态美的认识也从先前单纯的"以瘦为美"逐步转变到了对体表(特别是面部)轮廓、年轻化、平复凹陷的追求,由此,一批组织填充材料应运而生,诸如胶原蛋白、玻尿酸等人工合成填充材料.
目的 探讨神经内科重症监护病房医院获得性肺炎的病原菌分布以及对抗生素的耐药性,为抗感染治疗提供参考.方法 2016年1月~2017年12月入住湖南省第二人民医院神经内科重症监护病房合并院内获得性肺炎的患者79例,采集痰标本进行细菌分离及培养,并对其进行相关药敏试验.结果 共分离出89株病原菌,其中革兰氏阴性菌占87.64%,革兰氏阳性菌10.11%,真菌2.25%.病原菌以鲍曼不动杆菌(24.72%)、肺炎克雷伯菌(19.10%)、铜绿假单胞菌(17.98%),金黄色葡萄球菌为主(8.99%)为主;鲍曼不动杆菌对大部分抗菌药物耐药,铜绿假单胞菌对头孢哌酮舒巴坦和头孢他啶的耐药率较高,肺炎克雷伯菌耐药率低.金黄色葡萄球菌对青霉素耐药率高.结论 HAP致病菌以革兰氏阴性菌为主,其中鲍曼不动杆菌耐药严重,同时也应注意革兰氏阳性菌和真菌感染.
Objective To establish hypertrophic scar(HS)model on severe combined immunodeficiency(SCID)mice and investigate the feasibility. Methods Human split-thickness skin graft was transplanted onto the dorsum of SCID mice, the harvested xenograft was then assessed and given biopsy for histology by hematoxylin & eosin (HE) or Masson's trichrome staining 2 and 4 weeks after operation, and hydroxyproline quantification by colorimetry 4 weeks after operation. RT-PCR analysis was also performed to identify mRNA levels of transforming growth factor-β1(TGF-β1)and connective tissue growth factor (CTGF)2 and 4 weeks after operation. Results The xenograft showed a characteristic of human HS including a red, firm, elevated appearance, and dermal thickness, changed adnexal structures, hypervascularization, thinner collagen fibrils and disorganization of them. The content of hydroxyproline in experimental group increased significantly compared to the control group 4 weeks after operation(P<0.05).Moreover,RT-PCR showed significantly elevated mRNA levels for both TGF-β1 and CTGF in experimental group 2 and 4 weeks after operation (P<0.01). Conclusion This animal model has intrinsic properties that closely resemble HS formation as seen in humans, which shares additional merits of simple operation and flexible controllability and therefore can be expected to play a critic role in the research of human HS.
The intermolecular recognition and interaction between human transforming growth factor β‐1 (TGF‐β1) and its cognate receptor TβRII have been implicated in the pathological condition of hypertrophic scarring (HS). Here, we attempted to rationally derive peptide inhibitors from the complex interface of TGF‐β1 with TβRII to disrupt such interaction for the suppression of fibroblast activation involved in HS. A synthetic strategy that integrated computational design and fluorescence‐based assay was described to examine the structural basis and energetic property of TGF‐β1–TβRII crystal structure, from which a small peptide segment in the complex binding site was stripped artificially. Molecular dynamics simulations revealed that the linear peptide possesses a large intrinsic disorder that would incur considerable entropy penalty upon binding to TβRII; the peptide segment was then extended and cyclized by introducing a disulfide bond across its terminal residues that were premutated to cysteine. Normal mode analysis indicated that, as expected, the peptide flexibility was largely reduced upon the cyclization, and thus, the entropy penalty was minimized substantially, consequently promoting the spontaneous binding of peptide to TβRII. Fluorescence polarization assay confirmed that all linear peptides are typical non‐binders of TβRII (Kd = ND), while the designed cyclic peptides exhibit moderate or high affinity with Kd at micromolar level.
Objective To investigate the effect and targeting of iRGD-exosomes-doxorubicin (iRGD-exo-dox) on the inhibition of A375 cell line. Methods The exosomes were extracted from the iRGD-transfected A375 cells. The doxorubicin was wrapped by electroporation. Flow cytometry was used to detect the affinity of iRGD-exo-dox to A375 cells. The ability of iRGD-exo-dox on inhibiting the proliferation of A375 cells was analyzed. Results The affinity of iRGD-exo-dox to A375 cells was higher than the blank-exo-dox. The proliferation of A375 cells was obviously inhibited by iRGD-exo-dox. The inhibition effect was not observed in blank-exo-dox group. Conclusion iRGD-exo-dox can inhibit the proliferation of A375 cells by targeting function.
恶性黑色素瘤是皮肤黑色素细胞来源的高度恶性肿瘤,发病机制尚未清楚,黑色素细胞痣恶变、紫外线照射、病毒感染等多种因素均与其发生有密切关系。由于其具有转移早、病情隐匿的特点,早诊断、早治疗是恶性黑色素瘤治愈的关键。当前各种靶向治疗在抗肿瘤领域中发挥重要作用,如嵌合抗原抗体及携带药物的重组外泌体与恶性黑色素瘤细胞的靶向结合,已在体外实验中取得了显著效果。现综合国内外文献,就嵌合抗原受体修饰T细胞(CAR-T)和外泌体用于治疗恶性黑色素瘤的进展综述如下。
Hypertrophic scarring (HS) is a type of fibrosis that occurs in the skin, and is characterized by fibroblast activation and excessive collagen production. However, at present, therapeutic strategies for this condition are ineffective. Previous studies have identified that the mutual regulation of chronic inflammation, mechanical force and fibroblast activation leads to the formation of HS. Induced pluripotent stem cells (iPSCs) are novel bioengineered embryonic‑like stem cells, initially created from mouse adult fibroblasts. The current study demonstrated that iPSC‑conditioned medium (iPSC‑CM) may significantly suppress hypertrophic scar fibroblast activation. It was observed that in the presence of iPSC‑CM, the level of collagen I was markedly reduced and α‑smooth muscle actin, a marker for myofibroblasts (activated fibroblasts that mediate mechanical force‑induced HS formation), exhibited a significantly lower level of expression in human dermal fibroblasts (HDFs) activated with transforming growth factor‑β1. Additionally, iPSC‑CM attenuated the local inflammatory cell response by blocking the adhesion of human acute monocytic leukemia cell monocytes and fibroblasts in vitro. In addition, the contractile ability of HDFs may be reduced by iPSC‑CM. These observations suggest that iPSC‑CM may protect against processes leading to hypertrophic scarring by attenuating fibroblast activation, blocking inflammatory cell recruitment and adhesion and reducing the contractile ability of fibroblasts.
你知道吗?大约每4 000人中就有一个人没有耳朵(先天性外耳畸形、小耳畸形).这些人自出生起就背负着身心的双重煎熬,承受着一般人难以想象的巨大心理压力. 耳朵的外形与轮廓非常复杂,造一只看起来逼真的耳朵是整形外科最难的手术之一. 耳朵支架耳朵的特殊外形是耳朵内的软骨所赋予的,一般整形再造需采用自身的肋软骨雕刻而成,用这种方式再造耳所需时间短,3个月就能完成.