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*

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*

OBJECTIVETo investigate the clinical value of ultrasound-guided laser thermal ablation (LTA) in the treatment of small liver cancer at high-risk sites.

METHODSA total of 73 lesions ablated with LTA in 68 patients with small liver cancer. After the operation, the rates of complete ablation were compared between patients with lesions of different sizes and at different sites using contrast-enhanced ultrasound and the complications were recorded during the follow-up.

RESULTSThe complete ablation rates for carcinomas ≤1 cm, 1-2 cm, and 2-3 cm were 100%, 86.4%, and 82.7%, respectively, showing no significant differences among them (P>0.05). The complete ablation rates of lesions were similar between the high-risk and low-risk groups (85.7% vs 92.1%; P>0.05). The two groups showed no significant difference in the incidence of complications (9.1% vs 5.7%; P>0.05).

CONCLUSIONUltrasound-guided LTA can be a good option for treatment of small liver cancers at high-risk sites.

Contrast Media ; Follow-Up Studies ; Humans ; Laser Therapy ; methods ; Lasers ; Liver Neoplasms ; therapy ; Treatment Outcome ; Ultrasonic Therapy

This study aimed to examine the optimal conditions of laser-induced interstitial thermotherapy (LITT) via a single-needle delivery system, and the ablation-related pathological and ultrasonic changes. Ultrasound (US)-guided LITT (EchoLaser system) was performed at the output power of 2-4 Wattage (W) for 1-10 min in ex vivo bovine liver. Based on the results of the ex vivo study, the output power of 3 and 4 W with different durations was applied to in vivo rabbit livers (n=24), and VX2 tumors implanted in the hind limbs of rabbits (n=24). The ablation area was histologically determined by hematoxylin-eosin (HE) staining. Traditional US and contrast enhanced ultrasound (CEUS) were used to evaluate the treatment outcomes. The results showed: (1) In the bovine liver, ablation disruption was grossly seen, including a strip-like ablation crater, a carbonization zone anteriorly along the fiber tip, and a surrounding gray-white coagulation zone. The coagulation area, 1.2 cm in length and 1.0 cm in width, was formed in the bovine liver subjected to the ablation at 3 W for 5 min and 4 W for 4 min, and it extended slightly with the ablation time. (2) In the rabbit liver, after LITT at 3 W for 3 min and more, the coagulation area with length greater than or equal to 1.2 cm, and width greater than or equal to 1.0 cm, was found. Similar coagulation area was seen in the implanted VX2 carcinoma at 3 W for 5 min. (3) Gross examination of the liver and carcinoma showed three distinct regions: ablation crater/carbonization, coagulation and congestion distributed from the center outwards. (4) Microscopy revealed four zones after LITT, including ablation crater/carbonization, coagulation, edema and congestion from the center outwards. A large area with coagulative necrosis was observed around a vessel in the peripheral area with edema and hyperemia. (5) The size of coagulation was consistent well to the CEUS findings. It was concluded that EchoLaser system at low power can produce a coagulation area larger than 1.0 cm×1.0 cm during a short time period. The real-time US imaging can be used to effectively guide and assess the treatment.
Animals ; Bone Neoplasms ; diagnostic imaging ; pathology ; therapy ; Cattle ; Hindlimb ; pathology ; Laser Therapy ; instrumentation ; methods ; Liver Diseases ; diagnostic imaging ; therapy ; Rabbits ; Treatment Outcome ; Ultrasonic Therapy ; instrumentation ; methods ; Ultrasonography

The vast majority of the published papers dealing with the treatment of wounds in the past few decades reported that extracorporeal shock wave therapy (ESWT) used in wound repair is easy in manipulation, noninvasive, safe, effective, and well tolerated by patients. However, little is known about the mechanism of ESWT in wound healing to date. In this article, we reviewed the literature to identify the potential cellular and molecular mechanisms of ESWT in the process of wound healing, and the results of the literature showed that the mechanism of ESWT in promoting wound healing is the result of heterogeneous biological effects.
High-Energy Shock Waves ; therapeutic use ; Humans ; Skin ; Soft Tissue Injuries ; therapy ; Ultrasonic Therapy ; methods ; trends ; Wound Healing ; physiology

OBJECTIVETo investigate the effect and safety of extracorporeal shock wave (ESW) in the treatment of pain symptom of type III B prostatitis.

METHODSWe treated 50 cases of type III B prostatitis by ESW once a week for 4 weeks. Then we evaluated the clinical effect and safety of the therapy based on the NIH-CPSI scores, visual analogue scale (VAS) scores, IIEF-5 scores, prostate volume and morphous, state of urination, color of urine, results of routine semen analysis, and changes of cytokines (IL-6, TNF-α and IL-1β) in expressed prostatic secretion (EPS).

RESULTSAll the patients successfully accomplished the treatment. Compared with the baseline, decreases were observed after 4 weeks of cytokine treatment in the pain scores (14. 61 ± 1. 82 vs 9. 36 ± 1. 47, P <0. 01), urination symptom scores (4. 59 ± 1. 01 vs.4. 66 ± 0. 89, P >0. 05) , quality of life scores (6. 51 ± 1. 03 vs 4. 56 ± 1. 02, P <0. 01), NIH-CPSI (25. 43 ± 1. 72 vs 18. 28 ± 2. 32, P <0. 01 ), and VAS (6. 59 ± 1. 10 vs 3. 02 ± 1. 07, P < 0. 01). The concentration of IL-6 in the EPS was significantly increased ([55.82 ± 6. 28] vs [86.59 ± 4. 55] ng/ml, P <0. 01) , while the level of TNF-α ([3.89 ± 0. 12] vs [3. 19 ± 0.22] ng/ml, P<0.01) and that of IL-1β ([3.21 ± 1.01] vs [1.48 ± 0.95] ng/ml, P< 0. 01) remarkably reduced after treatment. However, there were no statistically significant differences in IIEF-5 scores (18. 58 ± 2. 03 vs 18. 51 1. 89, P >0. 05) or various sperm parameters before and after treatment (P >0. 05). And no significant changes were observed in the prostate volume, morphous or internal echoes.

CONCLUSIONThe ESW therapy is effective and safe for the pain symptom of type III B prostatitis.

Adult ; Body Fluids ; Humans ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Male ; Middle Aged ; Pain ; etiology ; metabolism ; Pain Management ; methods ; Prostatitis ; complications ; metabolism ; therapy ; Quality of Life ; Spermatozoa ; physiology ; Tumor Necrosis Factor-alpha ; metabolism ; Ultrasonic Therapy ; methods ; Urine