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Tumor immunotherapy is booming around the world. However, strategies to activate the immune system and alleviate the immunosuppression still need to be refined. Here, we demonstrate for the first time that low-intensity pulsed ultrasound (LIPUS, spatial average time average intensity (Isata) is 200 mW/cm2, frequency is 0.3 MHz, repetition frequency is 1 kHz, and duty cycle is 20%) triggers the immune system and further reverses the immunosuppressive state in the mouse models of breast cancer by irradiating the spleen of mice. LIPUS inhibited tumor growth and extended survival in mice with 4 T-1 tumors. Further studies had previously shown that LIPUS enhanced the activation of CD4+ and CD8+ T cells in the spleen and led to significant changes in cytokines, as well as induced upregulation of mRNA levels involved in multiple immune regulatory pathways in the spleen. In addition, LIPUS promoted tumor-infiltrating lymphocyte accumulation and CD8+ T cell activation and improved the dynamics of cytokines/chemokines in the tumor microenvironment, resulting in a reversal of the immunosuppressive state of the tumor microenvironment. These results suggest a novel approach to activate the immune response by irradiating the spleen with LIPUS. [ABSTRACT FROM AUTHOR]

Introduction: The low-intensity pulsed ultrasound (LIPUS) is one of the popular treatment modalities allowing to boost the proliferation, differentiation, and migratory activity of cells, which might be a powerful strategy for anti-aging. Seeking a novel setup for LIPUS would benefit the development of ultrasound therapeutics. Methods: Here, we proposed a novel underwater exposure setup of LIPUS. C57BL/6 mice were reared in the designated age-groups, which consisted of a middle-aged group (12–14 months) and an old-age group (20–23 months). The age-related changes of body composition, imbalance of energy supply and demand, imbalance of signal network maintaining internal stability, and representative phenotypes of neurodegeneration and neuroplasticity with the presence and absence of underwater LIPUS in middle-aged and aged groups were evaluated. Results: The results showed that there were obvious aging changes, imbalance of energy supply and demand, imbalance of signal network maintaining homeostasis, neurodegeneration, and damage of neural plasticity in the middle-aged and aged group with or without the LIPUS. Although middle-aged group and aged group responded differently to LIPUS, they mostly generated positive results in relieving bone loss, improving ovarian structure, regulated immune system, and enhanced endurance ability, which should have declined over age. Discussion: These findings indicate that underwater extracorporeal LIPUS exposure could be employed as single or combined anti-aging strategies that generated positive outcomes against the process of aging. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the efficacy and safety of focused low-intensity pulsed ultrasound (FLIPUS) with pulsed shortwave diathermy (PSWD) in subjects with painful knee osteoarthritis (OA). In a prospective randomized trial, 114 knee OA patients were randomly allocated to receive FLIPUS or PSWD therapy. The primary outcome was the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores. Secondary outcomes included the numerical rating scale (NRS) for pain assessment, time up and go (TUG) test, active joint range of motion (ROM) test, and Global Rating of Change (GRC) scale. Data were collected at baseline, 12 days, 12 weeks and 24 weeks. Patients receiving FLIPUS therapy experienced significantly greater improvements in the WOMAC total scores than patients receiving PSWD therapy at 12 days (mean difference, − 10.50; 95% CI − 13.54 to − 7.45; P = 0.000). The results of the NRS, TUG test, ROM test and GRC scale showed that participants treated with FLIPUS reported less pain and better physical function and health status than those treated with PSWD at 12 days (P = 0.011, P = 0.005, P = 0.025, P = 0.011, respectively). Furthermore, patients in the FLIPUS group showed significant improvements in the WOMAC total scores and NRS scores at 12 weeks (mean difference, − 7.57; 95% CI − 10.87 to − 4.26; P = 0.000 and − 1.79; 95% CI − 2.11 to − 1.47, respectively) and 24 weeks (mean difference, − 6.96; 95% CI − 10.22 to − 3.71; P = 0.000 and − 1.37; 95% CI − 1.64 to − 0.96; P = 0.000, respectively) of follow-up. There were no adverse events during or after the interventions in either group. This study concluded that both FLIPUS and pulsed SWD are safe modalities, and FLIPUS was more effective than PSWD in alleviating pain and in improving dysfunction and health status among subjects with knee OA in the short term. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032735. Registered 08/05/2020, http://www.chictr.org.cn/showproj.aspx?proj=53413. [ABSTRACT FROM AUTHOR]

Objectives: To explore the ameliorating effects of low‐intensity pulsed ultrasound (LIPUS) on Sprague Dawley rat myelosuppression induced by cell cycle specificity drugs (docetaxel, mitotic phase sensitive; and etoposide, gap 2 phase sensitive). Methods: Rats were respectively administered docetaxel (100 mg/kg) or etoposide (110 mg/kg) by intraperitoneal injection for 4 consecutive days. Then the rats were divided randomly into a LIPUS group and a non‐LIPUS group. In the LIPUS group, the right femoral metaphysis of rats was treated by LIPUS (acoustic intensity, 200 mW/cm2; frequency, 0.3 MHz; and duty cycle, 20%) for 20 minutes on 7 consecutive days from day 5. The rats of the non‐LIPUS group were treated without ultrasound output. A blood cell count, an enzyme‐linked immunosorbent assay, a real‐time quantitative polymerase chain reaction, and hematoxylin–eosin staining were applied to detect the results. Results: Low‐intensity pulsed ultrasound significantly promoted the counts of bone marrow nucleated cells, white blood cells, immunoglobulin A (IgA), IgG, granulocyte colony‐stimulating factor, stem cell factor, and intercellular cell adhesion molecule 1 and reduced the counts of vascular cell adhesion molecule 1 whether in the docetaxel or etoposide group (P <.05). Low‐intensity pulsed ultrasound only increased the expression level of IgM in the docetaxel group but decreased the level of interleukin 6 in the etoposide group (P <.05). Conclusions: Low‐intensity pulsed ultrasound has potential to be a noninvasive treatment for myelosuppression caused by different cell cycle–sensitive chemotherapy drugs. [ABSTRACT FROM AUTHOR]

Aims: We systematically investigated the effect of combined use of low-intensity pulsed ultrasound (LIPUS) and bone mesenchymal stem cells C3H10T1/2 on bone-defect healing.Methods: C3H10T1/2 cells were first induced into a stationary phase by incubation with low fetal bovine serum (5 ml/l) for five days and then sonicated with LIPUS for ten minutes once every day for five consecutive days. The same LIPUS treatment combined with C3H10T1/2 cells, which were incubated in regular fetal bovine serum (10 ml/l) were used to aid femoral fracture healing in Sprague-Dawley rats during four consecutive weeks. C3H10T1/2 cell proliferation activity was detected by MTT assay. Cell-cycle changes were determined, and cell proliferation index was calculated using flow cytometry. Bone reparation was evaluated by X-ray imaging and hematoxylin and eosin (H&E) staining during the healing process.Results: LIPUS promoted C3H10T1/2 cell proliferation, the mechanism of which was possibly the up-regulation of Bmi-1 gene expression. At the end of week two after combined use of LIPUS and C3H10T1/2, the femoral gap was reduced on X-ray images. According to H&E staining results, new bone had homogeneous and similar density compared with normal surrounding bone after combined use of LIPUS and C3H10T1/2. At the end of week four, bone defects could not be observed by X-ray in all four groups and repaired bone substance in all four groups could be observed by H&E staining.Conclusions: LIPUS treatment effectively promotes C3H10T1/2 cells to enter the growth/split phase from the stationary phase. This process enhances cell proliferation, which consequently promotes bone-defect healing. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore a law of energy deposition of high-intensity focused ultrasound (HIFU) in various tissues and the expression of such a law. A focused ultrasound (US) tumor therapeutic system was used to apply a focused US beam to tissues both in vivo and in vitro. The formation of individual ellipsoid-shaped regions of coagulative necrosis has been observed. Results showed that the volume of the ellipsoid-shaped coagulative necrosis region was different from that of the acoustic focal region (AFR), both in vitro and in vivo. Acoustic intensities ranging from 7 × 103 W/cm2 to 27.7 × 103 W/cm2 and exposure times from 1 to 20 s gave volumes of ellipsoid-shaped coagulative necrosis of 0.2 to 2000 mm3. Although the HIFU doses applied were identical, the volumes of individual ellipsoid-shaped coagulative necrotic regions varied with the structures of tissues, their functional status and the irradiation depths. Individual ellipsoid-shaped regions of coagulative necrosis induced by HIFU can be added to produce coagulative necrosis of an entire tumor. We define the individual ellipsoid-shaped coagulative necrosis produced by the US energy deposition of a single exposure as the “biological focal region” (BFR) of HIFU. This serves as the basic unit for HIFU ablation of tumors, and is plotted as a function of AFR, acoustic intensity, exposure time, irradiation depth, the tissue structure and its functional status. (E-mail: wangzhibiao@netease.com) [Copyright &y& Elsevier]