lncRNA NEAT1-let 7b-P21 axis mediates the proliferation of neural stem cells cultured in vitro promoted by radial extracorporeal shock wave

In previous studies, we found radial extracorporeal shock wave (rESW), can promote the proliferation of neural stem cells（NSCs）. Emerging evidence suggests that lncRNA NEAT1 can regulate NSCs proliferation. Whether lncRNA NEAT1 plays a role in the proliferation of NSC induced by shock waves is unclear. Cell Counting Kit-8（CCK 8） method was used to detect the proliferation of NSCs, and the relative protein and mRNA expression of related genes of Nestin, Cyclin D1 and P21 were detected by Western Blot and Quantitative real-time PCR（RT-qPCR）respectively. Immunofluorescence staining was used to observe the changes in the number of BrdU/nestin positive cells. Overexpression of NEAT1 and let 7b in cells were used to explore whether rESW can rescue the decreased number of NSCs.We found that the optimal dose of R15 transmitter promoting NSCs proliferation is 1.5 bar, 500 pulse, 2 Hz. 1.2-1.5bar showed a dose-dependent effect on the proliferation of NSCs, but it was negatively correlated with the proliferation effect of NSC when it was more than 1.5bar. We revealed that let 7b-P21 axis was involved in regulating the inhibition of NSC proliferation which was activated by NEAT1 in NSCs. In addition, we demonstrated that rESW treatment resulted in the decrease of NEAT1 expression, which was accompanied by the improved biological function including proliferation.Our results confirm that low-intensity rESW（1.5bar，500pulse，2Hz） can promote the proliferation of NSCs through NEAT1-let 7b-P21 axis.

Ultrasound-Guided Stellate Ganglion Block Combined with Extracorporeal Shock Wave Therapy on Postherpetic Neuralgia

Objectives. To evaluate the effect of ultrasound-guided stellate ganglion block combined with extracorporeal shock wave therapy (ESWT) on postherpetic neuralgia. Methods. Thirty-six patients with craniofacial postherpetic neuralgia, whose skin lesions were healed and natural course more than 1 month, were selected for the study and then randomly divided into 3 groups: the ultrasound-guided stellate ganglion block group (group A, n = 12), the extracorporeal shock wave therapy group (group B, n = 12), and the combined treatment group (group C, n = 12). Each group received basic drug treatment. The Visual Analogue Scale (VAS) and the Pain Disability Index (PDI) were used to evaluate the clinical effects of the 3 groups of patients before treatment, after twice treatments, after treatment for four times, and after treatment for six times. Results. The VAS and PDI were significantly declined in each group after the treatment ( P < 0.05 ), and the declination in group C was more obvious than the other two groups ( P < 0.05 ). After treatment for six times, the VAS score of group A, group B, and group C was 3.1 ± 1.2, 3.3 ± 1.3, and 1.9 ± 0.7, respectively. After treatment for six times, the PDI of group A, group B, and group C was 11.7 ± 8.4, 12.3 ± 7.8, and 4.6 ± 3.2, respectively. Three patients developed skin bruising and slight swelling, which were relieved by themselves. Conclusions. Ultrasound-guided stellate ganglion block combined with shock wave therapy could significantly improve the pain symptoms of patients with postherpetic neuralgia, which is a safe and effective treatment for postherpetic neuralgia.

Extracorporeal Shock Wave Therapy Salvages Critical Limb Ischemia in B6 Mice through Upregulating Cell Proliferation Signaling and Angiogenesis

(1) This study tests hypothesis whether extracorporeal shock wave (ECSW) therapy effectively salvages mouse critical limb ischemia (CLI). In vitro result demonstrated that the angiogenesis parameters (i.e., tubular length/cluster/network formation) and protein expressions of EGFR/VEGFR2/RAS/c-Raf/MEK/ERK/VEGF/p-PI3K/p-Akt/p-m-TOR were significantly and progressively increased with stepwise augmentation of ECSW energy (0.1/0.14/0.20 mJ/mm2/140 impulses). On the other hand, they were suppressed by administration of Avastin (20 μM). Adult male B6 mice (n = 24) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 [CLI + ECSW (0.12 mJ/mm2/120 impulses/at days 1/3/7 after CLI induction)] and group 4 [CLI + ECSW (0.12 mJ/mm2/120 impulses) + Avastin (1 mg/intramuscular-injection)] at days 1/3/7 after CLI induction] and quadriceps were harvested by day 14. The laser Doppler result showed that the ratio of left (ischemia) to right (normal) limb blood flow was highest in group 1, lowest in group 2, and significantly higher in group 3 than in group 4 by days 7/14 after the CLI procedure (p < 0.0001). The protein expressions of cell proliferation/migration/angiogenesis receptors (EGFR/VEGFR2), angiogenesis biomarkers (VEGF/CXCR4/SDF-1) and cell proliferation/growth/survival (Ras/c-Raf/MEK/ERK)/(PI3K/Akt/m-TOR) and cell motility/proliferation (p-FAK/p-Scr) signaling biomarkers were significantly higher in group 3 than in groups 1/2/4, and significantly lower in group 1 than in groups 2/4, but they did not show a difference between groups 2 and 4 (all p < 0.001). The small vessel density and cellular levels of endothelial cell surface marker (CD31+) exhibited an identical pattern of blood flow, whereas the angiogenesis (CXCR4+/VEGF+) displayed an identical pattern of VEGFR2 among the groups (all p < 0.0001). The in vitro and in vivo studies found ECSW salvaged the CLI mainly through upregulating Ras-Raf-MEK/ERK/cell motility, cell proliferation/growth pathways and angiogenesis.

Effects of β-Hydroxy β-Methylbutyric Supplementation in Combination with Conservative Non-Invasive Treatments in Athletes with Patellar Tendinopathy: A Pilot Study

The aim of the present study was to analyze the effect of conservative non-invasive treatments based on eccentric training, stretching and extracorporeal shock wave therapy (ESWT) supplemented with β-Hydroxy β-methylbutyric (HMB) or placebo (PLAC) on body composition, pain and muscular function (jump ability, muscular power and muscular strength) in athletes with patellar tendinopathy (PT). In a double-blind randomized trial, 8 athletes (4 males and 4 females) performed a physical rehabilitation for 4 weeks. They were randomly divided into two experimental groups (two males and two females in each one) that ingested HMB (HMBG) or PLAC (PLACG). In pre- and post-intervention were assessed body composition, pain, countermovement jump (CMJ), back-squat (BS) for analyzing peak power (W) (PPPP), load (kg) associated to PPPP (PPKG) and mean velocity (m/s) (PPMV) in addition to a 5-RM leg extension tests. An interaction intervention·supplementation (p = 0.049; Ƞ2p = 0.774) was observed in the height reached in the CMJ as an intervention effect in PPPP detected for the HMBG (p = 0.049). In addition, an enhancement in PPKG (p = 0.028; Ƞ2p = 0.842) was detected in the intervention, but not in PPMV, as an increase in the intervention in the 5-RM test (p = 0.001; Ƞ2p = 0.981) was observed. No changes were noted on body composition or pain (p > 0.05). The combination of eccentric training with stretching and ESWT increased concentric muscular power and strength after 4 weeks without changes in body lean mass or pain. In addition, HMB supplementation could enhance the power muscular performance in athletes with PT, optimizing the intervention adaptions.

Treatment of Sialolithiasis: What Has Changed? An Update of the Treatment Algorithms and a Review of the Literature

Treatment for sialolithiasis has undergone significant changes since the 1990s. Following the development of new minimally invasive and gland-preserving treatment modalities, a 40–50% rate of gland resection was reduced to less than 5%. Extracorporeal shock-wave lithotripsy (ESWL), refinement and extension of methods of transoral duct surgery (TDS), and in particular diagnostic and interventional sialendoscopy (intSE) are substantial parts of the new treatment regimen. It has also become evident that combining the different treatment modalities further increases the effectiveness of therapy, as has been especially evident with the combined endoscopic–transcutaneous approach. In the wake of these remarkable developments, a treatment algorithm was published in 2009 including all the known relevant therapeutic tools. However, new developments have also taken place during the last 10 years. Intraductal shock-wave lithotripsy (ISWL) has led to remarkable improvements thanks to the introduction of new devices, instruments, materials, and techniques, after earlier applications had not been sufficiently effective. Techniques involving combined approaches have been refined and modified. TDS methods have been modified through the introduction of sialendoscopy-assisted TDS in submandibular stones and a retropapillary approach for distal parotid sialolithiasis. Recent trends have revealed a potential for significant changes in therapeutic strategies for both major salivary glands. For the submandibular gland, ISWL has replaced ESWL and TDS to some extent. For parotid stones, ISWL and modifications of TDS have led to reduced use of ESWL and the combined transcutaneous–sialendoscopic approach. To illustrate these changes, we are here providing an updated treatment algorithm, including tried and tested techniques as well as promising new treatment modalities. Prognostic factors (e.g., the size or location of the stones), which are well recognized as having a strong impact on the prognosis, are taken into account and supplemented by additional factors associated with the new applications (e.g., the visibility or accessibility of the stones relative to the anatomy of the duct system).

Effectiveness of Radial Extracorporeal Shock Wave Therapy and Visual Feedback Balance Training on Lower Limb Post-Stroke Spasticity, Trunk Performance, and Balance: A Randomized Controlled Trial

Stroke remains one of the leading causes of disability in adults, and lower limb spasticity, affected stance, and balance impact everyday life and activities of such patients. Robotic therapy and assessment are becoming important tools to clinical evaluation for post-stroke rehabilitation. The aim of this study was to determine in a more objective manner the effects of visual feedback balance training through a balance trainer system and radial extracorporeal shock wave therapy (rESWT), along with conventional physiotherapy, on lower limb post-stroke spasticity, trunk control, and static and dynamic balance through clinical and stabilometric assessment. The study was designed as a randomized controlled trial. The experimental group underwent conventional physiotherapy, visual feedback balance training, and rESWT. The control group underwent conventional physiotherapy, visual feedback training and sham rESWT. The statistical analysis was performed using GraphPad Software and MATLAB. Primary clinical outcome measures were The Modified Ashworth Scale (MAS), passive range of motion (PROM), Visual Analogue Scale (VAS), and Clonus score. Secondary outcome measures were trunk performance, sensorimotor, and lower limb function. Stabilometric outcome measures were trunk control, static balance, and dynamic balance. Visual feedback training using the Prokin system and rESWT intervention, along with conventional physiotherapy, yielded statistically significant improvement both on clinical and stabilometric outcome measures, enhancing static and dynamic balance, trunk performance, sensorimotor outcome, and limb function and considerably diminishing lower limb spasticity, pain intensity, and clonus score in the experimental group.

Physical Considerations for In Vitro ESWT Research Design

In vitro investigations, which comprise the bulk of research efforts geared at identifying an underlying biomechanical mechanism for extracorporeal shock wave therapy (ESWT), are commonly hampered by inadequate descriptions of the underlying therapeutic acoustical pressure waves. We demonstrate the necessity of in-situ sound pressure measurements inside the treated samples considering the significant differences associated with available applicator technologies and cell containment. A statistical analysis of pulse-to-pulse variability in an electrohydraulic applicator yields a recommendation for a minimal pulse number of n = 300 for cell pallets and suspensions to achieve reproducible treatments. Non-linear absorption behavior of sample holders and boundary effects are shown for transient peak pressures and applied energies and may serve as a guide when in-situ measurements are not available or can be used as a controllable experimental design factor. For the use in microbiological investigations of ESWT we provide actionable identification of common problems in describing physical shockwave parameters and improving experimental setups by; (1) promoting in-situ sound field measurements, (2) statistical evaluation of applicator variability, and (3) extrapolation of treatment parameters based on focal and treatment volumes.

Treatment of Medial Collateral Ligament Injuries of the Knee with Focused Extracorporeal Shockwave Therapy: A Case Report

Medial collateral ligament (MCL) injuries are the most frequent ligamentous injuries of the knee. Focused extracorporeal shock wave therapy (f-ESWT) is progressively expanding its field of application to many musculoskeletal pathologies. Although there is evidence surrounding the efficacy of f-ESWT in tendinopathies, no studies have described the usefulness of ultrasound (US)-guided f-ESWT in the treatment of ligament injuries. Herein, we report a case of a MCL injury treated with f-ESWT. Moreover, our case shows the importance of using ultrasonography in determining the effect of treatment. A 60-year-old man with a focal area of lesion in the deep fibers underwent 4 weekly sessions of US-guided f-ESWT to the injured ligament area. His pain decreased to a visual analog scale (VAS) of 3 at the end of the treatment and was completely resolved at the 1-month follow-up visit, with these results being maintained at 4-month follow-up. The US examination showed an initial deposition of “newly formed tissue” at the site of previous injury of the proximal MCL insertion, and a reduction in MCL thickness together with an improvement in echostructure. Based on this result, we speculate that non-surgical ligament injuries could be a new indication for f-ESWT. However, further investigation on the effects of f-ESWT for ligament injuries is needed.