Ultrasonic Therapy

超声治疗
  • 文章类型: Journal Article
    探讨聚焦超声联合等离子射频消融技术对持续性应变性鼻炎生理稳定性及术后恢复的影响。对于对照实验,选择90例持续性应变性鼻炎患者,分为对照组(CG)和实验组(EG)。CG使用传统的射频消融技术,而EG采用聚焦超声技术结合射频消融技术治疗持续性应变性鼻炎。在EG和CG之间,比较和对比鼻腔症状的恢复,鼻部体征,术后不适,术后呼吸状态。手术后四分之一,EG和CG之间的体征评分有很大差异,治疗6个月后观察到特别显著的差异。手术一年后,在不同间隔的有效率比较中,EG和CG之间存在统计学差异,P值为.013。手术后6个月,EG和CG比较鼻功能的MTT时间分别为12.632.65和17.682.84,具有统计学上的显著差异。在MTR比较中EG和CG之间的差异具有统计学意义。比较不同处理时间后EG和CG之间的NNO值。EG患者的一氧化氮值随着时间的推移而下降,术后1个月和术后1年有统计学意义。从各种症状有效率的比较中可以明显看出,EG比CG具有更高的治疗有效率,术后总治疗效果差异有统计学意义。PONV的指标,PA,定向能力,呼吸恢复,嗅觉恢复在EG中比在CG中表现更好,差异有统计学意义。聚焦超声和等离子射频消融技术在治疗持续性应变性鼻炎中具有良好的治疗效果,并能显著降低MTT。这项技术可以有效改善鼻塞等症状,鼻流,患者头痛,治疗效果持久。治疗后住院时间明显缩短。
    Examine the effects of focused ultrasound in combination with plasma radiofrequency ablation technology on the physiological stability and postoperative recovery of persistent strain rhinitis. For a control experiment, 90 patients with persistent strain rhinitis were chosen and split into two groups: the control group (CG) and the experimental group (EG). The CG used conventional radiofrequency ablation technology, while the EG used focused ultrasound technology combined with radiofrequency ablation technology to treat persistent strain rhinitis. Between the EG and the CG, compare and contrast the recovery of nasal symptoms, nasal signs, postoperative discomfort, and postoperative respiratory status. One quarter after surgery, there was a substantial difference in physical sign ratings between the EG and the CG, and a particularly significant difference was seen after six months of treatment. One year following surgery, there was a statistical difference between the EG and the CG in the comparison of effective rates at various intervals, with a P value of .013. At 6 months following surgery, the MTT times in the EG and CG for the comparison of nasal function were 12.63 2.65 and 17.68 2.84, respectively, with statistically significant differences. The difference between the EG and the CG in the MTR comparison is statistically significant. In the comparison of NNO values between the EG and the CG after different treatment times. The nitric oxide value of the EG patients decreased over time, with statistical significance one month after surgery and one year after surgery. It is evident from the comparison of various symptom efficacy rates that the EG has a higher treatment effectiveness rate than the CG, and the total treatment effect difference following surgery has statistical significance. Indicators for PONV, PA, directional ability, respiratory recovery, and olfactory recovery performed better in the EG than in the CG, and the differences were statistically significant. Focused ultrasound and plasma radiofrequency ablation technology have a good therapeutic impact in the treatment of persistent strain rhinitis and can significantly reduce MTT. This technology can effectively improve symptoms such as nasal congestion, nasal flow, and headache in patients, and the therapeutic effect is long-lasting. The hospitalization time after treatment is significantly shortened.
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  • 文章类型: Journal Article
    背景:肌筋膜疼痛综合征(MPS)是颞下颌关节病的一种特殊类型。比较各种治疗方法的研究结果很少且有争议。因此,这项研究旨在比较超声治疗的有效性,稳定夹板,TheraBite装置,和咀嚼肌锻炼可降低MPS患者的疼痛强度并改善下颌骨活动度。
    方法:这是单盲的,随机化,平行组,2023年4月至2023年10月在固定修复学系进行的主动对照试验,大马士革大学。包括年龄超过18岁的肌筋膜疼痛患者,伴有有限的下颌张开和持续至少6个月的疼痛。使用在线随机软件将80例患者随机分为四组:超声治疗,稳定夹板,TheraBite装置,和咀嚼肌肉锻炼。只有结果评估人员被掩盖了治疗分配。运动方案是TMD患者的运动计划。在基线(t0)考虑了以下主要结局指标,在第一个(t1),秒(t2),和治疗的第四(t3)周,在随访的第二个(t4)和第五个(t5)月:使用视觉模拟量表进行疼痛强度,最大齿间开口,右侧运动,左横向运动以毫米为单位。
    结果:在超声治疗中,疼痛程度在t3时从重度变为轻度,稳定夹板,和TheraBite设备组。在咀嚼肌肉锻炼组中,它变成了适度的,超声治疗(p=0.012)和稳定夹板(p=0.013)组之间存在显着差异。此外,在随后的随访期间(t4和t5),下颌活动度持续改善.
    结论:在5个月的随访后,所有疗法都同样有效。然而,超声治疗和稳定夹板有实现快速改善的好处。
    背景:ISRCTN20833186。
    BACKGROUND: Myofascial pain syndrome (MPS) is a particular type of temporomandibular joint disorder. Research findings comparing various treatment approaches are scarce and controversial. Therefore, this study aimed to compare the effectiveness of ultrasound therapy, stabilization splint, TheraBite device, and masticatory muscle exercises in reducing pain intensity and improving mandibular mobility in patients with MPS.
    METHODS: It was a single-blind, randomized, parallel-group, active-controlled trial that took place between April 2023 and October 2023 at the Department of Fixed Prosthodontics, Damascus University. Patients older than 18 years old with myofascial pain accompanied by limited jaw opening and pain lasting for at least 6 months were included. Eighty patients were randomly assigned into four groups using online randomization software: ultrasound therapy, stabilization splint, TheraBite device, and masticatory muscle exercises. Only outcome assessors were masked to treatment allocation. The exercise regimen was the exercise program for patients with TMD. The following primary outcome measures were considered at the baseline (t0), at the first (t1), second (t2), and fourth (t3) week of treatment, and at the second (t4) and fifth (t5) month of follow-up: pain intensity using the visual analogue scale, maximum interincisal opening, right lateral movement, and left lateral movement measured in millimeters.
    RESULTS: The pain level changed from severe to mild at t3 in ultrasound therapy, stabilization splint, and TheraBite device groups. In the masticatory muscle exercises group, it changed to moderate, with a significant difference between ultrasound therapy (p = 0.012) and stabilization splint (p = 0.013) groups. In addition, the mandibular mobility continued to improve at the subsequent follow-up periods (t4 and t5).
    CONCLUSIONS: All therapies are equally effective after 5-month follow-up. However, ultrasound therapy and stabilization splints have the benefit of achieving rapid improvement.
    BACKGROUND: ISRCTN20833186.
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  • 文章类型: Journal Article
    背景:乳腺癌是全球最常见的恶性肿瘤,肺癌后。在乳腺癌的各种亚型中,HER2阳性乳腺癌(HER2BC)由于其增加的侵袭性和转移潜力而提出了特别具有挑战性的预后。本研究的目的是构建基于聚(偏二氟乙烯-三氟乙烯)(P(VDF-TrFE))的复合压电纳米粒子,用于HER2BC的成像和治疗。
    方法:通过重塑P(VDF-TrFE)压电纳米颗粒的晶体结构,改善亲水性,并结合成像功能,我们开发了集成成像和治疗功能的压电复合纳米粒子(PGd@tNBs)。体外表征包括对压电性能的评估,亲水性,成像性能,和这些颗粒的治疗效果。PGd@tNBs颗粒的靶向和治疗有效性在SK-BR3细胞系中进一步验证,随后在HER2阳性荷瘤小鼠中证实。
    结果:纳米颗粒表现出优异的生物相容性和令人印象深刻的多模态成像性能。磁共振成像(MRI)观察显示PGd@tNBs颗粒在HER2阳性肿瘤中显著积累,与传统超声造影剂相比,具有优越的超声造影性能,和小动物体内成像显示PGd@tNBs颗粒主要通过呼吸和尿液代谢排出。压电显微镜表征强调了PGd@tNBs颗粒的出色压电性能。在靶向结合HER2-BC后,超声刺激影响细胞膜电位,导致可逆电穿孔。这个,反过来,影响细胞内外钙离子的平衡和线粒体膜电位。在被细胞摄取后,PGd@tNB,当暴露于超声波时,触发了活性氧(ROS)的产生,导致谷胱甘肽和超氧化物歧化酶的消耗,并实现声动力治疗。值得注意的是,重复超声刺激,PGd@tNBs颗粒结合并进入细胞后,增加ROS的产生并将凋亡率提高约45%。
    结论:结论:开发的PGd@tNBs颗粒表现出出色的成像和治疗效果,具有精确诊断和个性化治疗HER2BC的潜力。
    BACKGROUND: Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2 BC)poses a particularly challenging prognosis due to its heightened invasiveness and metastatic potential. The objective of this study was to construct a composite piezoelectric nanoparticle based on poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for imaging and treatment of HER2 BC.
    METHODS: By reshaping the crystal structure of P(VDF-TrFE) piezoelectric nanoparticles, improving hydrophilicity, and incorporating imaging capabilities, we developed piezoelectric composite nanoparticles (PGd@tNBs) that integrate imaging and therapeutic functions. The in vitro characterization encompassed the assessment of piezoelectric properties, hydrophilicity, imaging performance, and therapeutic efficacy of these particles. The targeting and therapeutic effectiveness of PGd@tNBs particles were further validated in the SK-BR3 cell line and subsequently confirmed in HER2-positive tumor-bearing mice.
    RESULTS: The nanoparticle demonstrated excellent biocompatibility and impressive multimodal imaging performance. Magnetic resonance imaging (MRI) observations revealed significant accumulation of PGd@tNBs particles in the HER2 positive tumor, exhibiting superior contrast-enhanced ultrasound performance compared to traditional ultrasound contrast agents, and small animal in vivo imaging showed that PGd@tNBs particles were primarily excreted through respiration and urinary metabolism. Piezoforce Microscopy characterization highlighted the outstanding piezoelectric properties of PGd@tNBs particles. Upon targeted binding to HER2-BC, ultrasound stimulation influenced the cell membrane potential, leading to reversible electroporation. This, in turn, affected the balance of calcium ions inside and outside the cells and the mitochondrial membrane potential. Following ingestion by cells, PGd@tNBs, when exposed to ultrasound, triggered the generation of reactive oxygen species (ROS), resulting in the consumption of glutathione and superoxide dismutase and achieving sonodynamic therapy. Notably, repeated ultrasound stimulation, post PGd@tNBs particles binding and entry into cells, increased ROS production and elevated the apoptosis rate by approximately 45%.
    CONCLUSIONS: In conclusion, the PGd@tNBs particles developed exhibit outstanding imaging and therapeutic efficacy, holding potential for precise diagnosis and personalized treatment of HER2 BC.
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  • 文章类型: Journal Article
    偏瘫肩痛(HSP)是中风后的常见临床表现,经常引起相当大的不适和残疾。已经开发了各种治疗方法来解决HSP。
    本研究旨在比较HILT与US治疗在缓解卒中患者HSP方面的有效性。
    一项双盲随机对照试验纳入了发病后一年内患有HSP的卒中患者。参与者被随机分配到HILT(假美国)或美国治疗(假HILT)。两组均接受了10分钟的指定治疗方式,并在连续两周内每周5次每天进行肩部运动范围(ROM)锻炼。疼痛减轻是主要结果,以肩部ROM为次要结果。
    30名患者(11名女性,19名男性;平均年龄:60.80±11.51岁)。经过两周的干预,HILT组静息和运动时疼痛减轻显着改善,与每组内治疗前值相比,US组在运动和肩关节内旋过程中疼痛减轻方面。然而,HILT和US治疗组的任何评估参数均无显著差异.
    HILT和US治疗在减轻中风患者HSP的疼痛和改善肩部ROM方面的疗效相当。两种模式,当结合肩部ROM练习时,为在这一人群中管理HSP提供可行的选择。需要更大样本量的进一步研究来验证这些发现并探索长期结果。
    UNASSIGNED: Hemiplegic shoulder pain (HSP) is a prevalent clinical manifestation following stroke, often causing considerable discomfort and disability. Various therapeutic approaches have been developed to address HSP.
    UNASSIGNED: This study aimed to compare the effectiveness of HILT versus US therapy in alleviating HSP in stroke patients.
    UNASSIGNED: A double-blind randomized controlled trial enrolled stroke patients with HSP within one year post-onset. Participants were randomly assigned to HILT (with sham US) or US therapy (with sham HILT). Both groups received 10-minute sessions of their assigned therapy modality along with daily shoulder range of motion (ROM) exercises 5 times per week over two consecutive weeks. Pain reduction was the primary outcome, with shoulder ROM as secondary outcomes.
    UNASSIGNED: Thirty patients (11 women, 19 men; mean age: 60.80 ± 11.51 years) were included. After the two-week intervention, significant improvements were observed in pain reduction at rest and during motion in the HILT group, and in pain reduction during motion and shoulder internal rotation in the US group compared to pre-treatment values within each group. However, there was no significant difference between the HILT and US therapy groups in any evaluated parameter.
    UNASSIGNED: Comparable efficacy was found between HILT and US therapy in reducing pain and improving shoulder ROM for HSP in stroke patients. Both modalities, when combined with shoulder ROM exercises, offer viable options for managing HSP in this population. Further research with larger sample sizes is needed to validate these findings and explore long-term outcomes.
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  • 文章类型: Journal Article
    伤口感染,特别是那些由致病菌引起的,由于相关的并发症和不良的治疗结果,引起了相当大的公共卫生问题。在这里,我们开发了抗菌纳米粒子,即,PGTP,通过将胍衍生物与基于卟啉的声敏剂配位。合成的PGTP纳米粒子,以它们的强正电荷为特征,通过电荷干扰有效地破坏细菌的生物合成过程,证明对革兰氏阴性和革兰氏阳性细菌的功效。此外,PGTP纳米粒子在超声刺激下产生活性氧,导致生物膜完整性的破坏和病原体的有效消除。RNA-seq分析揭示了伤口愈合的详细机制,揭示了PGTP纳米粒子,当加上超声波时,通过干扰氨基酸的合成和转录来损害细菌代谢。这项研究提出了一种通过超声驱动的电荷干扰治疗来对抗伤口感染的新方法,由先进的抗菌纳米材料促进。
    Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    声动力疗法(SDT)与角化术的结合用于靶向癌症治疗是肿瘤学的重大进展。在这里,我们提出了一个双重反应的治疗系统,\"CytoNano\",它结合了注入有氮化铜纳米颗粒和富氧全氟化碳(Lip@Cu3N/PFC-O2)的阳离子脂质体,全部包裹在嗜中性粒细胞膜和酸响应性羧甲基纤维素的仿生涂层中。CytoNano利用中性粒细胞和酸响应材料的细胞模拟,能够精确靶向肿瘤及其酸性微环境。这种战略设计促进了Lip@Cu3N/PFC-O2在肿瘤内的靶向释放,增强癌细胞摄取和线粒体定位。因此,它放大了Cu3N驱动的SDT和角化术的治疗功效,同时保留了健康组织。此外,CytoNano的超声反应性增强肿瘤内氧合,克服生理障碍并启动诱导多个细胞死亡途径的组合的声动力-铜质子效应。因此,我们开创了一种精确的声动力学角化的仿生方法,彻底改变癌症疗法。
    The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, \"CytoNano\", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu3N/PFC-O2), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu3N/PFC-O2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu3N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano\'s ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.
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  • 文章类型: Journal Article
    在这里,我们报告了低强度脉冲超声(LIPUS)对患有Buerger病的外周动脉疾病患者症状的影响。进行了活性和非活性LIPUS的双盲和随机研究。我们评估了12例Buerger病患者在LIPUS照射24周期间腿部循环的症状。12例未接受LIPUS照射的患者作为对照。LIPUS治疗24周后,视觉模拟评分的疼痛强度显着降低。接受LIPUS治疗的患者的皮肤灌注压显着增加。对照组的症状和灌注参数没有显着差异。在接受LIPUS治疗的任何患者中均未观察到严重的不良反应。LIPUS是非侵入性的,改善Buerger病患者症状的安全有效的选择。
    Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease.
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  • 文章类型: Journal Article
    目的:这项研究调查了震级,方向,以及在使用压电超声牙周洁治器进行仪器测量期间施加的力的时间方面,将这种力量与文献中的建议进行了比较,并评估了专业(牙医或牙科卫生师)和结石硬度的影响。
    方法:在体外记录了10名牙科卫生师和6名牙医在使用压电超声洁牙器清创相对较软和硬的人工牙结石时施加的力。对三个轴的总力及其分量进行统计分析。
    结果:在软性人工牙结石清创期间,牙科卫生员施加的平均总力为0.34N(±0.18N,范围:0.13N至0.59N)和牙医0.28N(±0.33N,范围:0.06N至0.95N),牙科卫生师和牙医的总力超过0.5N,大约有23%和14%的时间,分别。在硬质人工牙结石清创期间,牙科卫生员施加的平均总力为0.63N(±0.40N,范围:0.28N至1.64N)和牙医0.57N(±0.17N,范围:0.34N至0.76N);两个职业的总力超过0.5N的时间。平均而言,牙科卫生员对硬的力比对软的人工结石施加的力高1.85倍(p=0.04),牙医施加的力高2.04倍(p=0.06)。然而,牙科卫生师和牙医在清创硬(p=1.00)和软(p=0.26)结石时使用了类似的力量。
    结论:硬质人工牙结石清创过程中施加的力明显高于软性人工牙结石清创过程中施加的力。牙医和牙科卫生师之间没有发现统计学上的显着差异。两组在软硬人工牙结石上施加的力经常超过推荐值。
    OBJECTIVE: This study investigated the magnitude, direction, and temporal aspects of the force applied during instrumentation with a piezoelectric ultrasonic periodontal scaler, compared this force with recommendations in the literature, and assessed the influence of the profession (dentist or dental hygienist) and calculus hardness.
    METHODS: The force applied by ten dental hygienists and six dentists during debridement of comparatively soft and hard artificial dental calculus with a piezoelectric ultrasonic scaler was recorded in-vitro. The total force and its components in three axes were statistically analysed.
    RESULTS: During debridement of soft artificial dental calculus, the mean total force applied by dental hygienists was 0.34 N (± 0.18 N, range: 0.13 N to 0.59 N) and by dentists 0.28 N (± 0.33 N, range: 0.06 N to 0.95 N), and the total force exceeded 0.5 N approximately 23% and 14% of the time for dental hygienists and dentists, respectively. During debridement of hard artificial dental calculus, the mean total force applied by dental hygienists was 0.63 N (± 0.40 N, range: 0.28 N to 1.64 N) and by dentists 0.57 N (± 0.17 N, range: 0.34 N to 0.76 N); the total force exceeded 0.5 N more than half of the time for both professions. On average, dental hygienists applied 1.85x (p = 0.04) and dentists 2.04x (p = 0.06) higher force on hard than on soft artificial calculus. However, dental hygienists and dentists used similar forces during the debridement of both hard (p = 1.00) and soft (p = 0.26) calculus.
    CONCLUSIONS: The force applied during the debridement of hard artificial dental calculus was statistically significantly higher than during the debridement of soft artificial dental calculus. No statistically significant difference between dentists and dental hygienists was found. The force applied by both groups on soft and hard artificial dental calculus frequently exceeded recommended values.
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  • 文章类型: Journal Article
    本研究旨在探讨可行性,功效,聚焦超声(FUS)治疗伴有持续症状的外阴低度鳞状上皮内病变(VLSIL)的安全性。
    这项回顾性分析包括24例接受FUS治疗的VLSIL患者。在每次后续访问中,评估了临床反应,包括症状和体征的变化.此外,根据第3次随访的外阴活检结果评估组织学反应.评估临床和组织学反应以阐明功效。
    共有22名患者完成了随访和治疗后的病理活检。治疗后,瘙痒的临床评分从2.55±0.51降至0.77±0.81(p<0.05)。此外,临床有效率和组织学有效率分别为86.4%和81.8%,分别。只有2例治愈的患者在随访期间第3年和第4年复发,并在再次治疗后治愈。在不利影响方面,只有一名患者在治疗后出现溃疡,对症抗炎治疗后愈合,没有疤痕,在任何患者中均未发现其他治疗并发症。在随访期间,没有患者发生恶性转化。
    这项研究表明FUS是可行的,有效,并且可以安全地治疗具有持续症状的VLSIL患者,为有症状的VLSIL的无创治疗提供了新的解决方案。
    UNASSIGNED: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms.
    UNASSIGNED: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy.
    UNASSIGNED: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period.
    UNASSIGNED: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.
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