Non-invasive Therapeutic Method Research Articles

Photostimulation of lymphatic clearance of β-amyloid from mouse brain: a new strategy for the therapy of Alzheimer’s disease

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder that poses a significant burden on socio-economic and healthcare systems worldwide. However, the currently available therapy of AD is limited, and new strategies are needed to enhance the clearance of β-amyloid (Aβ) protein and improve cognitive function. Photobiomodulation (PBM) is a non-invasive and effective therapeutic method that has shown promise in treating various brain diseases. Here, we demonstrate that 1267-nm PBM significantly alleviates cognitive decline in the 5xFAD mouse model of AD and is safe as it does not induce a significant increase in cortical temperature. Moreover, with the combination of 3D tissue optical clearing imaging and automatic brain region segmentation, we show that PBM-mediated reductions of Aβ plaques in different subregions of prefrontal cortex and the hippocampus are different. The PBM-induced lymphatic clearance of Aβ from the brain is associated with improvement of memory and cognitive functions in 5xFAD mice. Our results suggest that the modulation of meningeal lymphatic vessels (MLVs) should play an important role in promoting Aβ clearance. Collectively, this pilot study demonstrates that PBM can safely accelerate lymphatic clearance of Aβ from the brain of 5xFAD mice, promoting improvement of neurocognitive status of AD animals suggesting that PBM can be an effective and bedside therapy for AD.Graphical

Real-Time Acoustic Simulation Framework for tFUS: A Feasibility Study Using Navigation System

Transcranial focused ultrasound (tFUS), in which acoustic energy is focused on a small region in the brain through the skull, is a non-invasive therapeutic method with high spatial resolution and depth penetration. Image-guided navigation has been widely utilized to visualize the location of acoustic focus in the cranial cavity. However, this system is often inaccurate because of the significant aberrations caused by the skull. Therefore, acoustic simulations using a numerical solver have been widely adopted to compensate for this inaccuracy. Although the simulation can predict the intracranial acoustic pressure field, real-time application during tFUS treatment is almost impossible due to the high computational cost. In this study, we propose a neural network-based real-time acoustic simulation framework and test its feasibility by implementing a simulation-guided navigation (SGN) system. Real-time acoustic simulation is performed using a 3D conditional generative adversarial network (3D-cGAN) model featuring residual blocks and multiple loss functions. This network was trained by the conventional numerical acoustic simulation program (i.e., k-Wave). The SGN system is then implemented by integrating real-time acoustic simulation with a conventional image-guided navigation system. The proposed system can provide simulation results with a frame rate of 5 Hz (i.e., about 0.2 s), including all processing times. In numerical validation (3D-cGAN vs. k-Wave), the average peak intracranial pressure error was 6.8 ± 5.5%, and the average acoustic focus position error was 5.3 ± 7.7 mm. In experimental validation using a skull phantom (3D-cGAN vs. actual measurement), the average peak intracranial pressure error was 4.5%, and the average acoustic focus position error was 6.6 mm. These results demonstrate that the SGN system can predict the intracranial acoustic field according to transducer placement in real-time.

Influence-Based Nano Fuzzy Swarm Oxygen Deficiency Detection and Therapy

Oxygen deficiency is a serious health problem that may occur as a result of many diseases. In this article, we present an influence-based nano fuzzy swarm (INFS) for oxygen deficiency detection and therapy using a swarm of oxygen carrier nanomachines operating in three cognitive fields of control, influence, and interest. In particular, we propose a long short-term memory (LSTM) deep neural network for detecting apnea by analyzing the irregular peripheral oxygen saturation (SpO2) signal. Using the proposed sleep-in-the-loop strategy and the desaturated blood biomarkers, including oxygen and hydrogen ion concentrations, an in-silico multithreshold nano fuzzy swarm noninvasive therapeutic method is then performed. We also analytically prove the stability of the INFS using swarm control theory. We apply our strategy to sleep apnea, as one of the most common instances of oxygen deficiency. Furthermore, we compare the accuracy of INSF by using LSTM, bidirectional LSTM (BiLSTM), multilayer perceptron (MLP), convolutional neural network (CNN), and support vector machines (SVM). The detection and therapy results are then compared with other apnea detection methods. The input variables and structure of INSF, i.e., the number of rules and width of membership functions, are studied in terms of robustness to noise. As the results show, the proposed artificial intelligence (AI)-based noninvasive nano detection and therapy method could outperform the competing approaches in treating oxygen deficiency emergencies such as apnea.

Non-Invasive Hybrid Ultrasound Stimulation of Visual Cortex In Vivo.

The optic nerve is the second cranial nerve (CN II) that connects and transmits visual information between the retina and the brain. Severe damage to the optic nerve often leads to distorted vision, vision loss, and even blindness. Such damage can be caused by various types of degenerative diseases, such as glaucoma and traumatic optic neuropathy, and result in an impaired visual pathway. To date, researchers have not found a viable therapeutic method to restore the impaired visual pathway; however, in this paper, a newly synthesized model is proposed to bypass the damaged portion of the visual pathway and set up a direct connection between a stimulated visual input and the visual cortex (VC) using Low-frequency Ring-transducer Ultrasound Stimulation (LRUS). In this study, by utilizing and integrating various advanced ultrasonic and neurological technologies, the following advantages are achieved by the proposed LRUS model: 1. This is a non-invasive procedure that uses enhanced sound field intensity to overcome the loss of ultrasound signal due to the blockage of the skull. 2. The simulated visual signal generated by LRUS in the visual-cortex-elicited neuronal response in the visual cortex is comparable to light stimulation of the retina. The result was confirmed by a combination of real-time electrophysiology and fiber photometry. 3. VC showed a faster response rate under LRUS than light stimulation through the retina. These results suggest a potential non-invasive therapeutic method for restoring vision in optic-nerve-impaired patients using ultrasound stimulation (US).

Acupressure Versus Ondansetron Usage for Postoperative Nausea and Vomiting After Gynecologic Surgeries.

Introduction Anti-emetic interventions include pharmacologic and non-pharmacologic strategies. Acupressure is a non-pharmacologic and non-invasive therapeutic method that involves applying physical pressure to acupuncture points with fingers or devices. The pericardium (PC6) acupoint is located on the palm side of the wrist between the palmaris longus and flexor carpi radialis tendons, three fingers across the wrist starting at the wrist crease. Our first aim was to assess the effect of PC6 point acupressure on PONV after gynecological surgeries compared to intravenous (IV) ondansetron. Secondly, we aimed to assess the factors associated with the firstand second hours (early) postoperative nausea scores. Methods This was a prospective, randomized, and single-centered intervention study conducted between November 1, 2022, and December 31, 2022, in a tertiary care hospital. Sancaktepe Martyr Prof. Dr. Ilhan Varank Education and Research Hospital Ethical Committee provided ethical approval for this study on October 14, 2022 (No: E-46059653-020). Randomization was done using the lottery method.Patients, who were over the age of 18with an American Society of Anesthesiologists (ASA) physical score of I, II, or III status and had undergone gynecologic surgery under general anesthesia, were included. Patients, who were ASAIV, under continuous use of opioids or corticoids, underwent surgery with regional anesthesia, or declined to participate in the study, were excluded.There were two comparisons in this study. First, we divided patients into two groups according to anti-emetic prevention. Patients, who received IV 4 mg ondansetron (Group O), and patients, who placed acupressure bands at the P6 points on both forearms (Group B). The second comparison was done to assess the factors associated with early postoperative nausea. Patients were divided into two groups according to the mean early postoperative nausea scores as low (< 4, Group 1) and high/moderate (≥ 4, Group 2).PONV and pain scores were collected at five-time points: the first, second, sixth, twelfth, and twenty-fourth hours after surgery. Results Of 102 patients, 50were in Group O and 52were in Group B. There was no significant difference in postoperative pain, nausea, and vomiting scores. Fifty patients (50%), including 24 patients (48%) in Group O and 26 patients (52%) in Group B, experienced early moderate/high postoperative nausea in our study. According to the second comparison, 52 patients were in Group 1, and 50 patients were in Group 2. Operation time; first and second-hour pain scores; first, second, sixth, twelfth, and twenty-fourth-hourscores; and first and second-hour vomiting scores were all significantly different across groups. Conclusion The effect of PC6 point acupressure on early PONV compared to IV ondansetron was similar after gynecological surgeries. However, using only one anti-emetic treatment did not adequately relieve early PONV. Of all patients, 11(10%) required an extra anti-emetic medication at the ward. 50% of patients experienced early moderate/high postoperative nausea in our study. Motion sickness history, operation time, and early postoperative pain scores were associated with early PONV.

Nanomedicines for high‑intensity focused ultrasound cancer treatment and theranostics (Review).

High-intensity focused ultrasound (HIFU) is a promising and representative non-invasive therapeutic method for treating cancer with a high degree of efficacy. This non-invasive method induces tumour cell necrosis by increasing the local temperature and mechanical pressure. However, the clinical application of HIFU is limited given its low penetration depth and the incidence of off-target side effects. With their promising structural adjustability and targeting ability, nanomedicines have been adopted to improve the ablative efficacy of HIFU in the treatment of cancer. By selectively changing the acoustic environment (tissue structure, density and blood supply) of tumour tissue, these nanomedicines may allow for lower HIFU doses and treatment duration, while additionally achieving a higher degree of efficacy. The use of nanomedicines may also enable cancer theranostics of HIFU, allowing for precise cancer therapeutics. The present review aimed to provide an overview of advances in nanomedicines for HIFU cancer treatment and theranostics, stating their current limitations and future perspectives.

Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia.

Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What's more, both PDT-mediated oxygen consumption and microvascular damage aggravate tumor hypoxia, thus, further impeding therapeutic outcomes. Compared to type II PDT with high oxygen dependence and high oxygen consumption, type I PDT with less oxygen consumption exhibits great potential to overcome the vicious hypoxic plight in solid tumors. Type I photosensitizers (PSs) are significantly important for determining the therapeutic efficacy of PDT, which performs an electron transfer photochemical reaction with the surrounding oxygen/substrates to generate highly cytotoxic free radicals such as superoxide radicals (˙O2-) as type I ROS. In particular, the primary precursor (˙O2-) would progressively undergo a superoxide dismutase (SOD)-mediated disproportionation reaction and a Haber-Weiss/Fenton reaction, yielding higher cytotoxic species (˙OH) with better anticancer effects. As a result, developing high-performance type I PSs to treat hypoxic tumors has become more and more important and urgent. Herein, the latest progress of organic type I PSs (such as AIE-active cationic/neutral PSs, cationic/neutral PSs, polymer-based PSs and supramolecular self-assembled PSs) for monotherapy or synergistic therapeutic modalities is summarized. The molecular design principles and strategies (donor-acceptor system, anion-π+ incorporation, polymerization and cationization) are highlighted. Furthermore, the future challenges and prospects of type I PSs in hypoxia-overcoming PDT are proposed.

Non-Invasive Heat-Induced Numerous Tissue Ablation Simulation in a Medical Environment Using Different Focal Length High Intensity Focused Ultrasound Apparatus

In the field of biomedical, HIFU is a non-invasive therapeutic method that employs non-ionizing acoustic waves to increase the temperature. According to its high efficiency and cheap cost, it has been the main focus of this research. The key stages of this tumor ablation include mechanical and thermal effects. Simulations on tissue ablation with HIFU were implemented in this research to investigate how multiple tissue ablation works and how to enhance tumor ablation while avoiding injury to surrounding healthy tissue by altering the optimal intensity, power, focal length and lens radius of curvature. In order to find the optimal features of the proposed model, this analysis employs clinical applications. Numerous soft and hard tissues from the human body were chosen for this analysis. At a specified acoustic power and exposure period, each tissues optimal frequency (1.6 MHz to 3.5 MHz) and power (120 W to 140 W) were obtained for effective tissue ablation. This research performed all computations by changing the focal length from 55 mm to 65 mm. The outcomes of this therapy might require several weeks to comfortably remove tumor. This optimum result indicates that HIFU tumor ablation procedure has a high probability of success.

Managing anxiety disorders with the neuro-biofeedback method of Brain Boy Universal Professional

Biofeedback is a non-invasive therapeutic method used independently or as an adjunct alongside other methods. This study evaluated the efficacy of biofeedback in the treatment of anxiety disorders. The sample consisted of 85 individuals with anxiety symptoms who underwent neuro-biofeedback therapy using Brain Boy Universal Professional. Anxiety was assessed by both the Hamilton Rating Scale for Anxiety (HAM-A) and Zung Anxiety Self-Assessment Scale (SAS) before the initiation and after completing ten sessions with biofeedback. Before biofeedback and based on the HAM-A scale, 27.0% of the individuals showed mild to moderate anxiety, 16.5% medium anxiety, and 56.5% severe anxiety. After the completion of biofeedback, 90.6% of the individuals experienced mild to moderate anxiety, 5.9% medium anxiety, and 3.5% severe anxiety. Based on the SAS scale, before biofeedback, 42.4% of the individuals showed minimal to moderate anxiety, 21.2% marked severe anxiety and 36.5% most extreme anxiety. After the biofeedback, 68.2% of the individuals were within a normal range, 27.1% had minimal to moderate anxiety, 4.7% marked severe anxiety, and none in most extreme anxiety. Both HAMA-A and SAS scales showed statistically reduced anxiety levels after biofeedback therapy. Thus, the primary symptom of anxiety can be addressed by the biofeedback method.

Efficacy of Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex in Patients With Minimally Conscious State

BackgroundThe treatment of patients in a minimally conscious state (MCS) remains challenging. Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method in treating neurologic diseases by regulating the cortical excitability. The aim is to investigate the effect of tDCS in patients with MCS in this study.MethodsEleven patients in MCS were enrolled in the study. All the patients received 5 daily sessions of 20-min sham tDCS, followed by 10 sessions of 20-min real tDCS. The anodal electrode and cathodal electrodes were placed over the left dorsolateral prefrontal cortex (DLPFC) and the right eyebrow, respectively. Assessment of Coma Recovery Scale-Revised (CRS-R) scores and resting-state functional MRI (rs-fMRI) scans was conducted three times in each patient: before tDCS (baseline, T0), post-sham tDCS at week 1 (T1), and post-real tDCS at week 2 (T2). The whole-brain functional connectivity (FC) was obtained by bilaterally computing FC from six seed regions: precuneus, middle frontal gyrus, supplemental motor area, angular gyrus, superior temporal gyrus, and occipital lobe. One-way repeated measure ANOVA was used to compare the differences of CRS-R scores and FC at T0, T1, and T2. The false discovery rate correction of p < 0.001 was adopted for controlling multiple comparisons in FC analysis.ResultsFive patients with MCS showed obvious clinical improvement represented by increased CRS-R scores post- 2-week real tDCS. The CRS-R scores did not change post- 1-week sham treatment. No side effects were reported during the study. The FC of the bilateral supplementary motor area, right angular gyrus, and right superior temporal gyrus were significantly enhanced after 2-week real tDCS compared with that after 1-week sham-tDCS. In addition, FC of bilateral occipital lobe and right precuneus were significantly enhanced post- 2-week real tDCS compared with the baseline.ConclusionOur findings indicated that tDCS over DLPFC could serve as a potentially effective therapy for improving the consciousness state in patients with MCS. The FC in rs-fMRI can be modulated by tDCS at both the stimulation site (left DLPFC) and the distant regions.

Polydopamine-assisted co-deposition of polyacrylic acid inducing dentin biomimetic mineralization for tooth-like structure repair in vitro

The aging of the global population has caused dentin exposure and root caries to become significant patient-management issues in clinical dentistry. Biomimetic remineralization, as a non-invasive therapeutic method, is of great significance to solve the problem. Herein, a novel biomimetic-mineralizing strategy to induce the self-healing of dentin defects with similar tooth structure was developed through the easy one-step polydopamine (PDA)-assisted co-deposition of polyacrylic acid (PAA) (denoted as PDA@PAA) in vitro. Immersing demineralized dentin into PAA and dopamine (DA) mixed solutions. Hereafter, the modified demineralized dentin was immersed in the supersaturated solution of calcium and phosphate at 37 °C at designated time. Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and attenuated total reflection fourier transform infrared (ATR-FTIR) were performed to analyze the interaction and co-deposition between PDA and PAA. The remineralization of demineralized dentin was characterized by field emission scanning electron microscope (FE-SEM), TEM, X-ray diffraction (XRD), friction and wear test, nanoindentation, acid resistance. And the cytocompatibility of PDA@PAA was evaluated by cell counting kit-8 (CCK-8) and cell morphology observation. The results that PAA inhibited further PDA polymerization and aggregation, PDA@PAA were co-deposited onto the surface of demineralized dentin matrix. SEM and TEM showed that the demineralized-dentin modified with PDA@PAA was completely remineralized at 12 h, not only the dentin tubules were occluded, but more importantly, the demineralized dentin collagen matrix was remineralized. Moreover, after mineralization for 24 h, a dense mineral layer similar to enamel structure was regenerated on the surface of dentin and closely combined with dentin. The results of mechanical properties and acid resistance suggested that the mechanical properties of the regenerated enamel-like structure are close to that of enamel, and its acid resistance is better than that of enamel. This study demonstrated that the PDA-assisted co-deposition of PAA can offer an inexpensive, rapid, and efficient strategy for the management of illnesses related to exposed and demineralized dentin.

Potential Applications of Low-intensity Extracorporeal Shock-Wave Therapy in Urological Diseases via Activation of Tissue Resident Stem Cells

For many years, low-intensity extracorporeal shock-wave therapy (Li-ESWT) has been clinically applied as a noninvasive therapeutic method, for urological diseases. The major corresponding biological molecular mechanisms of Li-ESWT are to induce stem cell differentiation, neural regeneration, and angiogenesis. This narrative review aims to present an overview of the potential utility of Li-ESWT and its effects on stem cell therapies. Recent studies have also shown that the combination treatment of Li-ESWT and stem cell therapies can be a new option for the treatment of erectile dysfunction (ED), urinary incontinence, bladder dysfunction, and other diseases. The potential contributions of Li-ESWT on stem cell therapies for these diseases are studied, highlighting the influence of Li-ESWT on proliferation, viability, and differentiation capacity of certain stem cells. The potential mechanisms, including the increased expression of vascular endothelial growth factor, chemokine CXC motif ligand 5, and transforming growth factor-β1 are described herein. Li-ESWT can also activate many cellular signaling pathways. The combination of Li-ESWT and stem cell therapies is a promising strategy for urological diseases. However, a much greater understanding of the mechanisms by which Li-ESWT enhances the efficacy of stem cell therapy is still needed before this combined treatment can be recommended for large-scale clinical application.

Effects of Additional Radial Shockwave Therapy to Median Nerve Gliding Exercises on Hand Grip Strength in Carpal Tunnel Syndrome Patients

ABSTRACTIntroduction: Carpal Tunnel Syndrome (CTS) is one of the most common entrapment neuropathiesfound in the upper extremities. Patients with moderate and severe CTS usually experience disturbancesin motor strength. A non-invasive therapeutic method that has recently emerged in the treatment of CTSis Radial Shock Wave Therapy (RSWT). RSWT is a therapy using shock waves and can be added to otherforms of exercise. The addition of RSWT in CTS is expected to increase the grip strength. Research thatdirectly assesses the effect of adding RSWT and median nerve gliding exercises on hand grip strength inCTS patients has not been conducted.Methods: This study was a pre-test/post-test control group design. There were 22 moderate grade CTSsubjects divided into 2 groups, the control group was received median nerve gliding exercise (n=11) andthe treatment group was received additional RSWT on median nerve gliding exercise (n=11). Assessmentof grip strength by Jamar hand dynamometer was performed before and after 4 weeks of treatment. Themean differences before and after treatment, as well as between groups was compared statistically usingan unpaired t-test.Results: There was no significant difference in the handgrip strength of the control group (p = 0.094),and a significant difference in the treatment group (p = 0.009) before and after the intervention. However,there were no significant differences in grip strength between the two groups (p=0.065).Conclusion: There was no significant effect of adding RSWT on improving handgrip strength in CTSpatients who received a median nerve gliding exercise.Keywords: carpal tunnel syndrome, entrapment neuropathies, grip strength, nerve gliding exercise,radial shockwave therapy

Effects of Additional Radial Shockwave Therapy to Median Nerve Gliding Exercises on Hand Grip Strength in Carpal Tunnel Syndrome Patients

ABSTRACTIntroduction: Carpal Tunnel Syndrome (CTS) is one of the most common entrapment neuropathies found in the upper extremities. Patients with moderate and severe CTS usually experience disturbances in motor strength. A non-invasive therapeutic method that has recently emerged in the treatment of CTSis Radial Shock Wave Therapy (RSWT). RSWT is a therapy using shock waves and can be added to other forms of exercise. The addition of RSWT in CTS is expected to increase the grip strength. Research that directly assesses the effect of adding RSWT and median nerve gliding exercises on hand grip strength inCTS patients has not been conducted.Methods: This study was a pre-test/post-test control group design. There were 22 moderate grade CTS subjects divided into 2 groups, the control group was received median nerve gliding exercise (n=11) and the treatment group was received additional RSWT on median nerve gliding exercise (n=11). Assessmentof grip strength by Jamar hand dynamometer was performed before and after 4 weeks of treatment. The mean differences before and after treatment, as well as between groups was compared statistically using an unpaired t-test.Results: There was no significant difference in the handgrip strength of the control group (p = 0.094), and a significant difference in the treatment group (p = 0.009) before and after the intervention. However, there were no significant differences in grip strength between the two groups (p=0.065).Conclusion: There was no significant effect of adding RSWT on improving handgrip strength in CTS patients who received a median nerve gliding exercise.Keywords: carpal tunnel syndrome, entrapment neuropathies, grip strength, nerve gliding exercise,radial shockwave therapy

Involvement of hydrogen peroxide in sonodynamical effect with sinoporphyrin sodium in hypoxic situation

Sonodynamic therapy (SDT) represents a noninvasive therapeutic method via the activation of certain chemical sensitizers using low intensity ultrasound to generate various reactive oxygen species (ROS). In this work, we conducted systematic experiments to evaluate the production of hydrogen peroxide (H2O2) in sinoporphyrin sodium (DVDMS) mediated SDT (DVDMS-SDT). We found that the fluorescence intensities of H2O2 specific probe BES-H2O2 and Amplex Red increased significantly exposure to DVDMS-SDT while decreased with the introduction of catalase (H2O2 scavenger), indicating the production of H2O2. And the fluorescence intensity of H2O2 susceptible probes were positively correlated with DVDMS concentration, ultrasound intensity and irradiation time. Under the same molarity concentration, DVDMS has advantages over proto-porphyrin IX (PpIX) and hemoporrin monomethyl ether (HMME) in H2O2 production, indicating that the yield of H2O2 depends on the properties of sensitizer. More importantly, DVDMS-SDT is involved in the process of H2O2 even in the oxygen-free condition, showing its greater superiority for the treatment of tumor under hypoxia environment.

Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy

Sonodynamic therapy (SDT) has attracted widespread interest in biomedicine, owing to its novel and noninvasive therapeutic method triggered by ultrasound (US). Herein, the Ti3C2 MXene nanosheets (Ti3C2 NSs) are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment. With the high-temperature treatment, the oxygen defect of Ti3C2 MXene nanosheets (H–Ti3C2 NSs) is greatly increased. Therefore, the electron (e−) and hole (h+) generated by US can be separated faster due to the improved degree of oxidation, and then the recombination of e−-h+ can be prevented with the abundant oxygen defect under US irradiation, which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti3C2 NSs without high-temperature treatment. After PEGylation, the H–Ti3C2-PEG NSs show good stability and biocompatibility. In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H–Ti3C2-PEG NSs, which can improve the SDT efficacy. In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment, showing photothermal therapy (PTT) enhanced SDT. Most importantly, the H–Ti3C2-PEG NSs can be biodegraded and excreted out of the body, showing no significant long-term toxicity. Our work develops the defective H–Ti3C2 NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer, extending the biomedical application of MXene-based nanoplatforms.

Effectiveness of high-intensity laser therapy in patients with myogenic temporomandibular joint disorder: A double-blind, placebo-controlled study

PurposeThe aim of the study is to evaluate the effectiveness of high-intensity laser therapy (HILT) in the short and long term in the treatment of patients with the myogenic temporomandibular joint disorder(TMD). MethodsThis prospective, double-blind, controlled clinical study was conducted on patients with myogenic TMD at a university's oral and maxillofacial surgery clinic. Seventy-six patients were randomized into two groups (HILT, and control group), including 38 patients in one group. The patients were evaluated for pain, the range of motion of the jaw, disability, and quality of life. Assessments were performed before therapy (week 0) and after therapy (weeks 4 and 12). Data were evaluated using SPSS-20 and the level of significance was set at p <0.05. ResultsThere was no significant difference between the groups in terms of socio-demographic characteristics of the groups at the beginning of the study. In the 4th week, the VAS pain score was significantly decreased in the HILT group (47%) compared to the placebo HILT group (4%) (p <0.001). The maximum mouth opening was significantly increased in the HILT group (27%) compared to the placebo HILT group (4%) at week 12 (p <0.001). The HILT group showed a significant improvement in Jaw Functional Limitation Scale 20 (JFLS-20) and Oral Health Impact Profile (OHIP-14) compared to the placebo HILT group (p <0.001 and p <0.005 respectively). ConclusionAs a result of the study, it was concluded that HILT is a highly effective, non-invasive therapeutic method for patients with myogenic TMD.

Correlation between ELF-PEMF exposure and Human RPE Cell Proliferation, Apoptosis and Gene Expression.

Purpose Emerging evidence implies that electromagnetic fields (EMFs) can negatively affect angiogenesis. In this regard, the effects of extremely low frequency pulsed electromagnetic field (ELF–PEMF) exposure on the relative expression level of angiogenic factors involved in the pathogenesis of ocular disorders were evaluated in human retinal pigment epithelial (hRPE) cells in order to investigate a noninvasive therapeutic method for patients with several ocular diseases associated with neovascularization.MethodsAfter separating hRPE cells from globes, hRPE cells were exposed to 15 mT of ELF–PEMF (120 Hz) at 5, 10, and 15 min for seven days. Cell proliferation and apoptosis of treated cells were evaluated via ELISA assay. Moreover, relative expression changes of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 were performed using real-time RT-PCR.Results ELF–PEMF exposure had no significant effects on the apoptosis and proliferation rate of hRPE cells. Expression level of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 was downregulated following 5 min of ELF–PEMF exposure.ConclusionAs ELF–PEMF showed inhibitory effects on the expression of angiogenic genes in hRPE cells with no cytotoxic or proliferative side effects, it can be introduced as a useful procedure for managing angiogenesis induced by retinal pathogenesis, although more studies with adequate follow-up in animal models are needed.

Transcutaneous auricular vagus nerve stimulation for impaired glucose tolerance: a randomized controlled trial Protocol: 经皮耳迷走神经刺激治疗糖耐量受损:随机对照试验研究方案

Backgroundimpaired glucose tolerance (IGT) is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus (T2DM) easily if no intervention provided. In western medicine, drug therapy assisted with the intervention of lifestyle is predominated. However, drug therapy brings serious side effect and high prices, while lifestyle intervention is difficult to be insisted on by patients. Therefore, a green and effective intervention mode is urgently needed. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive and green therapeutic method based on the theory of traditional Chinese medicine (TCM), which can regulate glucose metabolism and reduce blood glucose, but the clinical effect of it has not been clarified yet at present. Hence, this randomized controlled trial (RCT) aims at exploring the effectiveness and safety of taVNS in the treatment of IGT. Methodsa total of 158 patients with IGT will be randomized into a taVNS group and a transcutaneous non-auricular vagus nerve stimulation (tnVNS) group, 79 cases in each one. In the taVNS group and the tnVNS group, electric stimulation would be applied to Yídăn (胰胆pancreas and gallbladder, CO11) and Pǐ (脾spleen, CO13) on auricular concha and Jiān (肩shoulder SF4,5) on auricular rim respectively. The electric stimulation parameters would be the same in the patients of two groups, for 30 min in each treatment, twice a day, 6 weeks as one course and 2 courses of treatment required totally. In week 0, 6 and 12 of intervention, the effectiveness indicators would be determined, i.e. fasting plasma glucose (FPG), 2 h plasma glucose (2hPG) and glycosylated hemoglobin (HbA1c) successively. On week 0 and 12, body mass index (BMI) would be calculated, respiration, pulse and blood pressure would be recorded separately. Discussionthrough observing the regulatory effect of taVNS on FPG, 2hPG, HbA1c and BMI as well as the adverse reactions, the effectiveness and safety of taVNS in treatment of IGT would be evaluated. This study will provide a safe, effective, convenient and nontoxic side effect intervention for clinical treatment of IGT and prevention from the occurrence and development of T2DM.Trial registration: This trial has been registered on http://register.clinicaltrials.gov. Clinical Registration Number: ClinicalTrials.gov NCT03343262.

On chip detection of glial cell-derived neurotrophic factor secreted from dopaminergic cells under magnetic stimulation

Glial cell-derived neurotrophic factor (GDNF) is a small protein potently promoting the survival of dopaminergic and motor neurons. GDNF can be secreted from different types of cells including the dopaminergic neural cell line, N27. N27 cells, a rat dopaminergic neural cell line, is regarded as a suitable in vitro model for Parkinson's disease (PD) research. For PD treatment, transcranial magnetic stimulation (TMS), a noninvasive therapeutic method, showed beneficial clinical effects, but the mechanism for its benefit is not understood. Because GDNF is a potent neurotrophic factor, it is of great value to evaluate if GDNF secretion from N27 cells can be affected by magnetic stimulation (MS). However, the current methods for detecting GDNF are time-consuming and expensive. In this paper we outline the detection of GDNF secretion from N27 cells by ultrasensitive nanopore thin film sensors (nanosensor) for the first time. As low as 2 pg/mL GDNF can be readily detected by the nanosensor. Furthermore, we show that MS can promote GDNF secretion from N27 cells. Specifically, the GDNF concentration in N27 cell-conditioned media under MS treatment shows statistically significant increase up to 2-fold after 5 days in vitro in comparison with the control. This nanosensor along with the in vitro PD model N27 cells provides a low-cost, easy-to-use, sensitive approach for studying potential cell biological mechanisms of the clinical benefits of MS on PD.