Low-intensity pulsed ultrasound (LIPUS) is a non-invasive sonodynamic therapy that has been approved by the U.S. Food and Drug Administration for clinical use. Clinical trials have demonstrated that LIPUS ameliorates mild-to-moderate erectile dysfunction without adverse events. Histological analysis of the corpus cavernosum suggests that the therapeutic benefits of LIPUS may be attributed to alleviation of fibrosis, enhanced neovascularization, and promotion of innervation. Further investigations have revealed that LIPUS facilitates cavernous tissue repair through non-thermal mechanisms, including a cavitation effect, acoustic streaming, mass transfer enhancement, and direct mechanical stimulation. Mechanobiological transduction triggers molecular signaling cascades within endogenous cavernous cells, thereby stimulating cell proliferation, angiogenesis, extracellular matrix remodeling, and stem cell differentiation. Although LIPUS has the potential to induce cavernous rehabilitation in the treatment of erectile dysfunction, further investigations are necessary to elucidate the mechanisms via which LIPUS regulates each type of cavernous cell to determine the optimal parameters for this innovative therapy.
Male ; Humans ; Erectile Dysfunction/therapy* ; Ultrasonic Therapy/methods* ; Penis/pathology* ; Ultrasonic Waves

Ultrasound has emerged as a non-invasive neural modulation technique. Its mechanisms of action in the brain involve mechanical, cavitation, and thermal effects, which modulate neural activity by activating mechanosensitive ion channels, enhancing cell permeability, and improving blood circulation. The ultrasound-piezo-electric systems, based on the coupling between ultrasound and piezoelectric materials, can generate wireless electrical stimulation to promote neural repair, significantly improving therapeutic outcomes for neurodegenerative diseases and showing potential as a replacement for traditional invasive deep brain stimulation techniques. The ultrasound-responsive piezoelectric drug delivery system combines mechano-electrical conversion capability of piezoelectric materials with the non-invasive penetration advantage of ultrasound. This system achieves synergistic therapeutic effects for neurodegenerative diseases through on-demand drug release and wireless electrical stimulation in deep brain regions. It can effectively overcome the blood-brain barrier limitation, enabling precisely targeted drug delivery to specific brain regions. Simultaneously, it generates electrical stimulation in deep brain areas to exert synergistic neuroreparative effects. Together, these capabilities provide a more precise, efficient, and safe solution for treating neurodegenerative diseases. This review summarizes the neural regulatory mechanisms, technical advantages, and research progress of the ultrasound-responsive piezoelectric drug delivery systems for neurodegenerative disease therapy, aiming to offer novel insights for the field.
Humans ; Neurodegenerative Diseases/drug therapy* ; Drug Delivery Systems/methods* ; Blood-Brain Barrier ; Ultrasonic Waves ; Brain ; Ultrasonic Therapy ; Deep Brain Stimulation/methods*

OBJECTIVES: To explore the efficacy of low-intensity pulsed ultrasound (LIPUS) combined with nystatin for treatment of vaginal Candida albicans biofilm infection. METHODS: In vitro cultured Candida albicans biofilm were treated with LIPUS, nystatin, or both, and the minimum inhibitory concentration (MIC) of nystatin was determined. Crystal violet staining, confocal laser microscopy (CLSM) and scanning electron microscopy were used to quantify the biofilm and observe the activity and morphological changes of the biofilms; DCFH-DA was used to detect the changes in reactive oxygen species (ROS). Twenty female New Zealand White rabbits with vaginal inoculation of Candida albicans biofilm were randomized into 4 groups for treatment with normal saline, LIPUS, nystatin, or both LIPUS and nystatin. The changes in vulvar symptoms of the rabbits were observed, and the histopathological and ultrastructural changes of the vagina before and after treatment were observed using HE staining and transmission electron microscopy. RESULTS: In the combined treatment group, the MIC₅₀ and MIC₈₀ of nystatin in Candida albicans biofilms were both reduced by 50% compared with those in nystatin group, and the biofilm clearance rate increased by 26% and 68% compared with nystatin and LIPUS groups, respectively. Compared with nystatin and LIPUS treatment alone, the combined treatment produced stronger effects for inhibiting biofilm activity, causing structural disruption and promoting ROS production. In the rabbit models, the combined treatment more effectively improved vulvar symptoms and inflammatory infiltration, reduced residual vaginal hyphae/strains, and improved ultrastructure of the vaginal epithelium than LIPUS and nystatin treatment alone. CONCLUSIONS LIPUS combined with nystatin produces a significant synergistic antifungal effect against Candida albicans biofilm both in vitro and in vivo.
Animals ; Rabbits ; Female ; Biofilms/drug effects* ; Candida albicans/physiology* ; Nystatin/therapeutic use* ; Candidiasis, Vulvovaginal/microbiology* ; Ultrasonic Waves ; Antifungal Agents/therapeutic use* ; Vagina/microbiology* ; Ultrasonic Therapy ; Microbial Sensitivity Tests ; Combined Modality Therapy

Musculoskeletal disorders (MSDs) are characterized by extensive pathological involvement and high prevalence and cause a significant disease burden. Long-term drug administration often causes by adverse effects with poor therapeutic efficacy. Low-intensity pulsed ultrasound (LIPUS), as a specialized therapeutic modality, delivers acoustic energy at a low intensity in a pulsed wave mode, thus ensuring stable energy transmission to the target tissues while minimizing thermal effects. This non-invasive approach has demonstrated significant potential for MSD treatment by delivering effective physical stimulations. Extensive animal and clinical studies have demonstrated the efficacy of LIPUS for accelerating the healing process of fresh fractures and nonunions, promoting soft tissue regeneration and suppressing inflammatory responses. Emerging evidence suggests promising applications of LIPUS in skeletal muscle injury treatment and promoting tissue regeneration and repair. This review outlines the recent advancements and mechanistic studies of LIPUS for treatment of common MSDs including fractures, nonunions, muscle injuries, and osteoarthritis, addressing also the technical parameters of commercially available LIPUS devices, current therapeutic approaches, the existing challenges, and future research directions.
Humans ; Ultrasonic Therapy/methods* ; Musculoskeletal Diseases/therapy* ; Ultrasonic Waves ; Osteoarthritis/therapy* ; Muscle, Skeletal/injuries*

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro; promote stem cell proliferation, differentiation, and migration; maintain stem cell activity; alleviate the problems of insufficient seed cell source, differentiation, and maturation; and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.
Cell Proliferation ; Humans ; Signal Transduction ; Stem Cells/radiation effects* ; Ultrasonic Therapy/methods* ; Ultrasonic Waves

OBJECTIVE: To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design. METHODS: Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators. RESULTS: Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed. CONCLUSION Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.
Administration, Cutaneous ; Adult ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Intestinal Neoplasms ; complications ; secondary ; Intestinal Obstruction ; drug therapy ; etiology ; Male ; Middle Aged ; Ultrasonic Therapy ; methods

The development of low-frequency ultrasound imaging technology and the improvement of ultrasound contrast agent production technology mean that they play an increasingly important role in tumor therapy. The interaction between ultrasound and microbubbles and their biological effects can transfer and release microbubbles carrying genes and drugs to target tissues, mediate the apoptosis of tumor cells, and block the embolization of tumor microvasculature. With the optimization of ultrasound parameters, the development of targeted microbubbles, and the emergence of various composite probes with both diagnostic and therapeutic functions, low-frequency ultrasound combined with microbubble contrast agents will bring new hope for clinical tumor treatment.
Antineoplastic Agents/therapeutic use* ; Apoptosis ; Autophagy ; Cell Membrane Permeability ; Cell Proliferation ; Contrast Media/administration & dosage* ; Drug Delivery Systems ; Humans ; Microbubbles ; Microcirculation ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms/therapy* ; Patient Safety ; Transfection ; Ultrasonic Therapy/methods*

BACKGROUND: Pain, limitations in opening, asymmetrical jaw movements, and temporomandibular joint (TMJ) sounds are the most common findings in temporomandibular joint disorders (TMDs), which causes excruciating pain, inflammation of the surrounding muscles, posterior fibers, and synovial fluid. This study aimed to evaluate and compare the effects of ultrasound heat therapy and low-level laser therapy (LLLT) in reducing TMD-related pain. METHODS: This prospective study included 42 patients (age range, 25–45 years), who were divided into two groups of 21 patients each. All patients were prescribed a non-steroidal anti-inflammatory drug (NSAID) twice a day for 5 days for temporary relief of pain prior to the commencement of treatment. Patients were kept on a soft diet and asked to restrict mouth opening during the same period. Fifteen sessions of LLLT (Group A) or ultrasound therapy (Group B) were administered to the affected side. RESULTS: Post-therapy, the mean visual analog scale score for group A and group B was 4.81 (2.01) and 6.19 (1.20), respectively; the difference was statistically significant and favoring the LLLT group. Similarly, the mean mouth opening for group A and group B was 3.99 (0.40) and 3.65 (0.41), respectively; the difference was statistically significant and favoring the LLLT group. CONCLUSION: Our study recommends LLLT for treating TMD-related pain with no underlying bony pathology.
Diet ; Hot Temperature ; Humans ; Inflammation ; Jaw ; Low-Level Light Therapy ; Mouth ; Muscles ; Pathology ; Prospective Studies ; Synovial Fluid ; Temporomandibular Joint Disorders ; Temporomandibular Joint ; Ultrasonic Therapy ; Ultrasonography ; Visual Analog Scale

OBJECTIVE: The study aimed to determine the role of low frequency ultrasound in patients with Chronic Rhinosinusitis with Nasal Polyposis (CRS-NP) and recovery after Endoscopic Sinus Surgery (ESS) using Sino Nasal Outcome Test 22 (SNOT-22) questionnaires, modified Lund MacKay endoscopic appearance and histopathologic examination.
METHODS:
Design: Single Blinded Randomized Controlled Trial
Setting: Tertiary Government Hospital
Participants: 42 adult Filipinos aged 19 to 76 years old diagnosed with Chronic Rhinosinusitis with grade 2 and 3 Nasal Polyposis and failure of maximal medical management (3-month course of antibiotics, nasal douche, topical steroids and other modalities) between June 2013 to June 2015 were randomized into two groups of 21 participants each-- the ultrasoundtreated group and control group. Specimens (nasal polyps) from both groups were obtained and processed with Hematoxylin-Eosin (H&E) and gram staining. Specimens from the ultrasoundtreated group received low frequency ultrasound (1 MHz, 1.0 watt/cm2 , 20% pulsed mode for 5 minutes at 370 C) post-extraction and prior to staining. In phase II, the ultrasound group also received the same ultrasound treatment while the control group underwent ultrasound at 0 MHz frequency, 0 watt/cm2 , both twice a week for 3 weeks, beginning one (1) week post operatively.
RESULTS: Paired T-test showed a statistically significant difference between control and treatment groups in epithelial thickness with a p-value of 2.29E-10 (average of 73.34um for controls and 31.1um for the treatment group) at 95% confidence interval. The inflammatory cell count also differed significantly between control and treatment groups (average 293.85 and 29.65 inflammatory cells per high-power field in 10 random microscopic fields, respectively), p-value of 1.05E-17 on paired T-test; CI 95%. In phase II of the study, SNOT-22 results showed significant differences in improvement of symptoms in ultrasound-treated patients after EndoscopicSinus Surgery (weekly mean scores of 38.05, 21, 11.3, and 10.45) and in modified Lund Mackay endoscopic appearance scores (weekly mean scores of 7.88, 4.35, 3.02, 2.08). Two-way analysis of variance showed significant differences between control and treatment groups for both  SNOT-22 (p = 1.07E-80; 9.71E-119; CI 95%) and modified Lund Mackay endoscopic appearance scores (p = 3.89E-60; 1.85E-95; CI 95%). Both groups accomplished SNOT-22 forms and were evaluated via modified Lund MacKay endoscopic appearance at 1 week (week 0 of treatment), 2 weeks, 3 weeks, and 1 month post operatively (week 3 of treatment).
CONCLUSION: Low frequency therapeutic ultrasound demonstrated possible efficacy as an agent in disrupting epithelial architecture in patients with CRS-NP as well as in symptom improvement after endoscopic sinus surgery patients based on histopathologic evaluation, SNOT-22 and modified Lund MacKay endoscopic appearance scores. Low frequency ultrasound may be an adjuvant to conventional medical treatment in CRS-NP.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Nasal Polyps ; Hematoxylin ; Paranasal Sinuses ; Sinusitis ; Endoscopy ; Anti-bacterial Agents ; Cell Count ; Ultrasonic Therapy

Low-intensity extracorporeal shockwave therapy (LI-ESWT) is a novel treatment for erectile dysfunction (ED). With the property of angiogenesis, LI-ESWT acts on vasculogenic ED by improving penile hemodynamics and endothelial function. LI-ESWT is proved to be safe and effective in the treatment of vasculogenic ED in various prospective clinical studies, including randomized, double-blind, and sham-controlled trails. With more multi-centered larger-sample randomized controlled trials, LI-ESWT will play a valuable role in the treatment of ED.
Erectile Dysfunction ; therapy ; High-Energy Shock Waves ; therapeutic use ; Humans ; Male ; Penis ; physiopathology ; Prospective Studies ; Randomized Controlled Trials as Topic ; Ultrasonic Therapy