This work was financially supported by the Key Project of Medical Research Jointly from Chongqing Health Commission and Chongqing Science and Technology Bureau (2022ZDXM037), the Key Projects of Scientific Research Fund of Traditional Chinese Medicine of Wuhan Health Commission (WZ22A03), and Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0592).

All research procedures involving human participants comply with the ethical standards of the Ethics Committee of Chongqing Hospital of Traditional Chinese Medicine and the principles of the Declaration of Helsinki (1964) and its subsequent amendments and have received approval for the study from the aforementioned Ethics Committee. Image data collection was performed with both verbal and written consent from the patients, and photographs taken for teaching purposes as a routine part of the examination were obtained using the Multispectral Dermoscope.
1. Patient selection
<ol>
	<li>Set the following inclusion criteria5:
	<ol>
		<li>Select patients based on the presence of facial light to dark brown, well-defined patches, typically with symmetrical distribution, absence of inflammation, and scaling.</li>
		<li>Select patients based on the absence of significant subjective symptoms such as itching, burning, and pain.</li>
		<li>Select patients considering that melasma predominantly occurs in females, primarily after puberty.</li>
		<li>While selecting patients, consider seasonal variations in the condition-often worse in summer and milder in winter.</li>
		<li>Exclude patients if other conditions (such as nevus fuscoceruleus zygomaticus, Riehl&#39;s melanosis, and pigmentary photodermatitis) that may cause hyperpigmentation are present.</li>
	</ol>
	</li>
</ol>
2. Preparation for roller microneedle treatment
<ol>
	<li>Preoperative communication
	<ol>
		<li>Understand the patient&#39;s treatment goals and cosmetic aspirations and gather complete medical history, including medication history, allergies, contraindications, and past cosmetic treatments.</li>
		<li>Inform the patients about the treatment&#39;s effects, steps, potential complications, recovery time, duration, and costs. Discuss specific treatment plans and alternative options to ensure all patient queries are addressed, helping them establish realistic expectations and achieve higher satisfaction.</li>
		<li>Ask patients to sign an informed consent form.</li>
	</ol>
	</li>
	<li>Environmental requirements
	<ol>
		<li>Set aside a quiet, well-lit treatment room for the operation of the roller microneedle and disinfect it for 30 min with ultraviolet light before the procedure.</li>
		<li>Ask the patients to wear shoe covers and hats upon entering the treatment room.</li>
	</ol>
	</li>
	<li>Preparation of the necessary items and medication for treatment
	<ol>
		<li>Check and prepare all the materials listed in the Table of Materials.</li>
	</ol>
	</li>
	<li>Makeup removal and cleansing
	<ol>
		<li>If the treatment area was covered with makeup, thoroughly remove it with makeup remover before cleansing.</li>
		<li>For non-makeup wearers, clean the treatment area with a gentle cleansing product.</li>
	</ol>
	</li>
	<li>Multispectral dermatoscopy recording 
	NOTE: The Multispectral dermoscope uses different light sources to capture facial ultra-high pixel images.
	<ol>
		<li>Prior to treatments and after three treatments, use the Multispectral dermoscope to take photos of the patient&#39;s front, left (45&#176;), and right (45&#176;) from three different angles and record the values of patients&#39; UV-shallow and -deep spots and brown spots</li>
	</ol>
	</li>
	<li>Application of topical anesthesia
	<ol>
		<li>Apply 5% lidocaine cream evenly to the treated area, with a total dosage of 30-40 g, and wrap it with cling film to enhance the anesthesia effect for 40-60 min. 
		NOTE: Some patients may exhibit symptoms of allergy to the topical anesthetic. Patients may experience severe itching, burning, or stinging at the site of application. If such reactions occur, promptly remove the anesthesia and provide appropriate symptomatic treatment.</li>
		<li>Before the next treatment, ensure proper moisturization of the skin in the anesthesia application area.</li>
	</ol>
	</li>
	<li>Preparation of microneedle solution
	<ol>
		<li>Extract 5 mL of 5% tranexamic acid solution using a syringe and set it aside for use.</li>
	</ol>
	</li>
	<li>Preparation of microneedle instruments
	<ol>
		<li>Select a 0.5 mm roller microneedle (Figure 1) and soak it in 0.1% benzalkonium bromide solution for approximately 20 min to disinfect it.</li>
		<li>Rinse the microneedle 3x with physiological saline to remove the disinfectant. 
		&#8203;NOTE: Avoid cross-contamination by using a single roller microneedle for each patient to prevent unnecessary damage to the skin due to blunt needles and to prevent the spread of diseases between patients.</li>
	</ol>
	</li>
	<li>Removal of topical anesthesia
	<ol>
		<li>After a sufficient duration of topical anesthesia application, remove the cling film and scrape off the anesthetic with a spatula. Use gauze soaked in 0.9% saline solution to wipe off any remaining anesthetic from the face.</li>
	</ol>
	</li>
	<li>Disinfection
	<ol>
		<li>Expose the treatment area, wrap the hair with a disinfectant towel when treating the face, and disinfect the facial skin with a 0.1% benzalkonium bromide cotton ball 3x from the top to the hairline edge, to the lower jaw edge, and chin, following the principle of &#34;bottom-up, inward-outward&#34; to prevent infection.</li>
	</ol>
	</li>
</ol>
3. Roller microneedle procedure
<ol>
	<li>Have the therapist wash their hands and wear a hat, mask, and sterile gloves.</li>
	<li>After informing the patient about beginning the procedure, instruct the patient to close their eyes and treat in the order of left cheek, right cheek, forehead, jaw, upper lip, and nose. Inject an appropriate amount of tranexamic acid solution onto the skin using a syringe, apply evenly by hand, and then rinse the roller microneedle with physiological saline, roll it in a short distance along the horizontal, vertical, and oblique directions in the treatment area.</li>
	<li>Gradually perform the treatment in different areas, applying the solution while rolling to enhance absorption. Repeat 3-5x in one area, preferably with skin flushing and no obvious bleeding. Apply force evenly, neither too heavy nor too light, and do not drag a microneedle on the skin.</li>
</ol>
4. Efficacy evaluation
<ol>
	<li>Use a combination of roller microneedles and topical tranexamic acid solution 3x for the treatment of melasma, once every 4 weeks, as a course of treatment.</li>
	<li>Use the multispectral dermatoscope before and after treatment, 3x to observe the efficacy according to the values of the patients&#39; UV shallow and deep spots and brown spots. The smaller the values, the lighter the melasma.</li>
	<li>Statistically analyze the changes in the UV-shallow and -deep spots and brown spots before and after treatment.</li>
</ol>

Enhancing Melasma Treatment with Tranexamic Acid and Microneedling Therapy

<ol>
	<li>Passeron, T., Picardo, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Melasma,+a+photoaging+disorder.">Melasma, a photoaging disorder.</a> Pigment Cell &amp; Melanoma Research. 31 (4), 461-465 (2018).</li><li>Pigment Disease Group. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dermatovenereology+Professional+Committee+of+Chinese+Society+of+Integrative+Medicine,+Vitiligo+Research+Center+of+the+Dermatology+and+Venereal+Disease+Branch+of+the+Chinese+Medical+Association,+Pigment+Disease+Working+Group+of+the+Dermatology+and+Venereal+Disease+Branch+of+the+Chinese+Medical+Association,+Chinese+Medical+Doctor+Association.+Consensus+on+diagnosis+and+treatment+of+melasma+in+China+(2021+vision).">Dermatovenereology Professional Committee of Chinese Society of Integrative Medicine, Vitiligo Research Center of the Dermatology and Venereal Disease Branch of the Chinese Medical Association, Pigment Disease Working Group of the Dermatology and Venereal Disease Branch of the Chinese Medical Association, Chinese Medical Doctor Association. Consensus on diagnosis and treatment of melasma in China (2021 vision).</a> Chinese Journal Dermatology. 54 (2), 110-115 (2021).</li><li>Vineet, K. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microneedle+arrays+for+cutaneous+and+transcutaneous+drug+delivery,+disease+diagnosis,+and+cosmetic+aid.">Microneedle arrays for cutaneous and transcutaneous drug delivery, disease diagnosis, and cosmetic aid.</a> Journal of Drug Delivery Science and Technology. 79, 104058 (2023).</li><li>Skin Laser Medical Aesthetics Group, Dermatology and Venereology Branch, Chinese Medical Association, Skin Laser Technology Application Research Center of the Chinese Medical Association. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chinese+dermatologists'+consensus+on+laser+and+IPLS+treatment+and+skin+repairment+of+melasma.">Chinese dermatologists' consensus on laser and IPLS treatment and skin repairment of melasma.</a> Journal Practical Dermatology. 13 (2), 65-69 (2020).</li><li>Pigment Disease Group. Dermatovenereology Professional Committee of Chinese Society of Integrative Medicine. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+diagnosis+and+efficacy+criteria+for+melasma+(revised+in+2003).">Clinical diagnosis and efficacy criteria for melasma (revised in 2003).</a> Chinese Journal of Dermatology Venereology Integrative Traditional and Western Medicine. 3 (1), 66 (2004).</li><li>McKesey, J., Tovar-Garza, A., Pandya, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Melasma+treatment:+an+evidence-based+review.">Melasma treatment: an evidence-based review.</a> American Journal of Clinical Dermatology. 21 (2), 173-225 (2020).</li><li>Budamakuntla, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+randomised,+open-label,+comparative+study+of+tranexamic+acid+microinjections+and+tranexamic+acid+with+microneedling+in+patients+with+melasma.">A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with melasma.</a> Journal of Cutaneous and Aesthetic Surgery. 6 (3), 139-143 (2013).</li><li>Cohen, B. E., Elbuluk, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microneedling+in+skin+of+color:+a+review+of+uses+and+efficacy.">Microneedling in skin of color: a review of uses and efficacy.</a> Journal of the American Academy of Dermatology. 74 (2), 348-355 (2016).</li><li>Lee, H. C., Thng, T. G. S., Goh, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oral+tranexamic+acid+(TA)+in+the+treatment+of+melasma:+a+retrospective+analysis.">Oral tranexamic acid (TA) in the treatment of melasma: a retrospective analysis.</a> Journal of the American Academy of Dermatology. 75 (2), 385-392 (2016).</li><li>Banihashemi, M., Zabolinejad, N., Jaafari, M. R., Salehi, M., Jabari, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+therapeutic+effects+of+liposomal+tranexamic+acid+and+conventional+hydroquinone+on+melasma.">Comparison of therapeutic effects of liposomal tranexamic acid and conventional hydroquinone on melasma.</a> Journal of Cosmetic Dermatology. 14 (3), 174-177 (2015).</li><li>Ebrahimi, B., Naeini, F. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+tranexamic+acid+as+a+promising+treatment+for+melasma.">Topical tranexamic acid as a promising treatment for melasma.</a> Journal of Research in Medical Sciences. 19 (8), 753-757 (2014).</li><li>Na, J. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+tranexamic+acid+on+melasma:+a+clinical+trial+with+histological+evaluation.">Effect of tranexamic acid on melasma: a clinical trial with histological evaluation.</a> Journal of the European Academy of Dermatology and Venereology. 27 (8), 1035-1039 (2013).</li><li>Kim, E. H., Kim, Y. C., Lee, E. S., Kang, H. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+vascular+characteristics+of+melasma.">The vascular characteristics of melasma.</a> Journal of Dermatological Science. 46 (2), 111-116 (2007).</li><li>Yuan, C., Wang, X. M., Yang, L. J., Wu, P. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tranexamic+acid+accelerates+skin+barrier+recovery+and+upregulates+occluding+in+damaged+skin.">Tranexamic acid accelerates skin barrier recovery and upregulates occluding in damaged skin.</a> International Journal of Dermatology. 53 (8), 959-965 (2014).</li><li>Tohgasaki, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enolase-1+expression+in+the+stratum+corneum+is+elevated+with+parakeratosis+of+atopic+dermatitis+and+disrupts+the+cellular+tight+junction+barrier+in+keratinocytes.">Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes.</a> International Journal of Cosmetic Science. 40 (2), 178-186 (2018).</li><li>Lima, E. V. A., Lima, M. M. D. A., Paix&#227;o, M. P., Miot, H. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+the+effects+of+skin+microneedling+as+adjuvant+therapy+for+facial+melasma:+a+pilot+study.">Assessment of the effects of skin microneedling as adjuvant therapy for facial melasma: a pilot study.</a> BMC Dermatology. 17 (1), 14 (2017).</li><li>Saleh, F., Abdel-Azim, E., Ragaie, M., Guendy, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Topical+tranexamic+acid+with+microneedling+versus+microneedling+alone+in+treatment+of+melasma:+clinical,+histopathologic,+and+immunohistochemical+study.">Topical tranexamic acid with microneedling versus microneedling alone in treatment of melasma: clinical, histopathologic, and immunohistochemical study.</a> Journal of Egypt Women's Dermatologic Society. 16 (2), 89 (2019).</li><li>Bailey, A. J. M., Li, H. O., Tan, M. G., Cheng, W., Dover, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microneedling+as+an+adjuvant+to+topical+therapies+for+melasma:+A+systematic+review+and+meta-analysis.">Microneedling as an adjuvant to topical therapies for melasma: A systematic review and meta-analysis.</a> Journal of the American Academy of Dermatology. 86 (4), 797-810 (2022).</li></ol>

The authors have no conflicts of interest to declare.

The pathogenesis of melasma is complex, and treatment methods include systemic medication, topical depigmenting agents, chemical peels, and laser therapy. Unfortunately, no single treatment is universally effective for all patients, and satisfactory results cannot be always guaranteed6. Phototherapy shows a decreasing trend in treating melasma, and some patients experience worsening of melasma after phototherapy. This is due to an increase in individuals with sensitive skin and impaired skin barri...

Melasma, also known as chloasma, is a chronic and acquired facial hyperpigmentation skin condition. Clinically, it presents as symmetrical, light to dark brown patches with unclear borders, distributed on the cheeks, forehead, and jawline. The incidence rate among Asian women of childbearing age can be as high as 30%1. The disease is easily diagnosed but difficult to cure. The pathogenesis of melasma is not yet fully understood, but three main factors contribute to its development: genetic susceptibility, exposure to sunlight, and hormonal changes. Increased melanin synthesis, vascular proliferation at the site of skin lesions, inflammatory reactions, and impaired skin barrier function all play a role in the occurrence of melasma2.
Currently, treatment options for melasma include laser therapy and medications, among which, transdermal administration is a widely used method. However, the main challenge lies in the barrier function of the stratum corneum, which hinders drug penetration. Microneedle therapy creates multiple micro-channels in the skin within a short period, disrupting the stratum corneum, inducing collagen production, and increasing skin permeability. This approach holds promise in allowing drugs to diffuse into the skin and then rapidly reseal, thus avoiding the introduction of toxic or irritating substances3.
Commonly used microneedle tools include the electronic water light injection microneedle, roller microneedle, electrically assisted nanocrystalline microneedle, plum blossom microneedle, and single needle microneedle4. The roller microneedle is characterized by less trauma, good curative effect, convenient operation, and can be combined with some other drugs to treat melasma. It has a good therapeutic prospect for melasma and is worth more promotion and use in clinical practice. This article introduces the operation and precautions of roller microneedles combined with tranexamic acid in the treatment of melasma and demonstrates the efficacy of roller microneedle combined with tranexamic acid in the treatment of melasma through clinical cases.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>5 mL syringe</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Benzalkonium bromide solution</td>
			<td>Chongqing Traditional Chinese Medicine Hospital</td>
			<td>H20050531</td>
			<td>0.1%</td>
		</tr>
		<tr>
			<td>cling film</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Compound lidocaine cream</td>
			<td>Beijing Ziguang Pharmaceutical Co., Ltd.</td>
			<td>H20063466</td>
			<td>5.0%</td>
		</tr>
		<tr>
			<td>disinfectant towel</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>disposable curved disc</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Multispectral Dermoscope</td>
			<td>CBS Medical Skin Analysis, Wuhan, China</td>
			<td>CBS-2022</td>
			<td></td>
		</tr>
		<tr>
			<td>Roller microneedle</td>
			<td>Guangzhou Yuanxiang Biotechnology Co., Ltd</td>
			<td>221001</td>
			<td>(model: 0.22 x 0.5 mm, Figure 1)</td>
		</tr>
		<tr>
			<td>Sodium chloride solution</td>
			<td>Hubei Tiansheng Pharmaceutical Co., Ltd.</td>
			<td>H42021838</td>
			<td>0.9%</td>
		</tr>
		<tr>
			<td>sterile cotton swab</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>sterile gauze</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>sterile gloves</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>tongue depressor</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tranexamic acid solution</td>
			<td>Shanghai Hyundai Hasen (Shangqiu) Pharmaceutical Co., Ltd.</td>
			<td>H20184047</td>
			<td>5.0%</td>
		</tr>
		<tr>
			<td>treatment vehicle</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

roller microneedle combined with tranexamic acid solution in treating melasma

Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective management. The precise underlying causes of melasma remain elusive, and the current therapeutic approaches predominantly encompass pharmaceutical and laser interventions, with limited efficacy. Transdermal administration stands as a prevalent treatment method for melasma, often facilitated by the application of microneedles. Among these, tranexamic acid emerges as a frequently employed therapeutic agent. A subset of microneedles, known as roller microneedles, plays a significant role in this approach by delicately puncturing the epidermis with multiple fine needles, synergizing with drug delivery. This methodology not only enhances drug absorption but also augments treatment efficacy while minimizing tissue trauma. These attributes forecast promising avenues for the treatment of melasma. This article primarily introduces the combination of roller microneedle and tranexamic acid solution in the treatment of melasma and demonstrates the efficacy of roller microneedle and tranexamic acid solution in the treatment of melasma through clinical cases.

Case 1, a 57-year-old female with a medical history of 10 years, was selected for treatment and efficacy evaluation. The efficacy of the combination of roller microneedle and tranexamic acid solution was evaluated before treatment and after three treatment sessions (Figure 2, Figure 3, and Figure 4) and observed from different angles using a multispectral dermatoscope. A reduction of 35.91 mm2, 163.32 mm2, and ...

Watch this Scientific Journal Video about Roller Microneedle Combined with Tranexamic Acid Solution in Treating Melasma at JoVE.com

Author Spotlight: Non-Surgical Treatment of Melasma&#8211; Microneedling with Tranexamic Acid

This article presents a protocol to conduct the treatment of melasma by using roller microneedles in combination with tranexamic acid solution and evaluate the efficacy.

Roller Microneedle Combined with Tranexamic Acid Solution in Treating Melasma

Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective ...

Our research focus on non-surgery therapy for pigmentated disease. We tested the efficacy of roller microneedling combined with tranexamic acid solution in treating melasma. We will investigate the effectiveness and the max easiness of using a combination of roller microneedles and tranexamic acid solution for treating melasma.

roller-microneedle-combined-with-tranexamic-acid-solution-treating

Research

JoVE Journal

Medicine

573 Views.  Chongqing Hospital of Traditional Chinese Medicine. Our research focus on non-surgery therapy for pigmentated disease. We tested the efficacy of roller microneedling combined with tranexamic acid solution in treating melasma. We will investigate the effectiveness and the max easiness of using a combination of roller microneedles and tranexamic acid solution for treating melasma.

Video: Author Spotlight: Non-Surgical Treatment of Melasma– Microneedling with Tranexamic Acid

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill1.
Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone2. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting3-5. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab6. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis7. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients8,9. Bevacizumab however failed to prolong overall survival in a recent phase III trial26. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians&#8217; choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm10.
There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy11,12, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.

A novel methodology that is employed for the treatment of recurrent glioblastomas is described. This treatment approach employs the application of alternating electric tumor treating fields (TTFields), known as TTF Therapy in combination with bevacizumab, a targeted agent that is currently FDA approved as monotherapy.

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA ...

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Self-assembling peptides (SAPs) are promising vehicles for the delivery of hydrophobic therapeutics for clinical applications; their amphipathic properties allow them to dissolve hydrophobic compounds in the aqueous environment of the human body. However, self-assembling peptide solutions have poor blood compatibility (e.g., low osmolarity), hindering their clinical application through intravenous administrations. We have recently developed a generalized platform for hydrophobic drug delivery, which combines SAPs with amino acid solutions (SAP-AA) to enhance drug solubility and increase formulation osmolarity to reach the requirements for clinical uses. This formulation strategy was thoroughly tested in the context of three structurally different hydrophobic compounds &#8211; PP2, rottlerin, and curcumin &#8211; in order to demonstrate its versatility. Furthermore, we examined effects of changing formulation components by analyzing 6 different SAPs, 20 naturally existing amino acids at low and high concentrations, and two different co-solvents dimethyl sulfoxide (DMSO) and ethanol. Our strategy proved to be effective in optimizing components for a given hydrophobic drug, and therapeutic function of the formulated inhibitor, PP2, was observed both in vitro and in vivo. This manuscript outlines our generalized formulation method using SAP-AA combinations for hydrophobic compounds, and analysis of solubility as a first step towards potential use of these formulations in more functional studies. We include representative solubility results for formulation of the hydrophobic compound, curcumin, and discuss how our methodology serves as a platform for future biological studies and disease models.

This protocol describes a clinically-applicable means of dissolving hydrophobic compounds in an aqueous environment using combinations of self-assembling peptide and amino acid solutions. Our method resolves a major limitation of hydrophobic therapeutics, which lack safe, efficient means of solubility and delivery methods into clinical settings.

Self-assembling peptides (SAPs) are promising vehicles for the delivery of hydrophobic therapeutics for clinical applications; their amphipathic ...

Tai Chi with Mindfulness Training to Manage Diabetic Peripheral Neuropathy

Effects of Mindfulness Training Combined with Tai Chi in Patients with Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. One of its crucial therapy approaches is mind-body exercise. Recently, various exercise modalities, including stepping, resistance, aerobics, balance, and whole-body vibration, were investigated to construct the most suitable form of exercise for patients with DPN. The purpose of this study is to describe a standard protocol for mindfulness training combined with Tai Chi. The convenience sampling method was used to select 90 patients with DPN who met the inclusion and exclusion criteria from three communities. The three communities were randomly divided into the control group (CG), the Tai Chi group (TCG), and the mindfulness training combined with the Tai Chi group (MTCG). The CG was given routine health education guidance once a month, a total of three times. Based on the CG, the TCG practiced Tai Chi three times; the MTCG received mindfulness training combined with Tai Chi exercise a week for a total of 12 weeks. Before the intervention and 12 weeks after the intervention, the clinical symptoms, neurological function, attention awareness level, pain, and quality of life of the subjects were evaluated by Toronto Clinical Scoring System (TCSS), Mindful Attention Awareness Scale (MAAS), Visual analog scale (VAS), Diabetes Specificity Quality of life Scale (DSQL) and tumor necrosis factor-&#945;. Overall, the addition of mindfulness training to Tai Chi effectively enhances the exercise effects of Tai Chi. Therefore, mindfulness training combined with Tai Chi is worthy of promotion and application.

Author Spotlight: Integrating Tai Chi with Mindfulness Training to Achieve an Effective Mind-Body Exercise 

When studying exercise for treating diabetic peripheral neuropathy (DPN), achieving mind-body exercise is essential. This study proposes a protocol for mindfulness training combined with Tai Chi to achieve mind-body exercise.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. One of its crucial therapy approaches is mind-body ...

Acupoint Application Combined with Acupoint Massage for Treating Constipation in a Patient with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a common and frequent disease in elderly patients, with a tendency for progressive exacerbation. Constipation that reduces the quality of life and triggers the risk of diseases is a common concomitant symptom in patients with COPD. Currently, western medical treatment does not achieve the desired results for patients. A high recurrence rate accompanies it, whereas traditional Chinese medicine (TCM) has a long history and rich experience in treating chronic diseases. Both acupoint application and acupoint massage are characteristic therapies of TCM, with minor side effects, high safety, simple operation, and outstanding advantages. They are effective in treating constipation for patients with COPD and are considered an ideal alternative therapy for patients with chronic constipation. The purpose of this article is to introduce the method of acupoint application combined with acupoint massage for the treatment of constipation in patients with COPD, including the selection of points, items, treatment time, and operation procedure.

Here we demonstrate acupoint application combined with acupoint massage for treating constipation in a patient with chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a common and frequent disease in elderly patients, with a tendency for progressive exacerbation. ...

Establishment of the KOA Model in Rabbits Using the Modified Videman Method

Application of Acupotomy in a Knee Osteoarthritis Model in Rabbit

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department, which seriously reduces the quality of life of people with KOA. Among several pathogenic factors, the biomechanical imbalance of the knee joint is one of the main causes of KOA. Acupotomology believes that restoring the mechanical balance of the knee joint is the key to treating KOA. Clinical studies have shown that acupotomy can effectively reduce pain and improve knee mobility by reducing adhesion, contracture of soft tissues, and stress concentration points in muscles and tendons around the knee joint. 
In this protocol, we used the modified Videman method to establish a KOA model by immobilizing the left hindlimb in a straight position. We have outlined the method of operation and the precautions related to acupotomy in detail and evaluated the efficacy of acupotomy in conjunction with the theory of "Modulating Muscles and Tendons to Treat Bone Disorders" through the detection of the mechanical properties of quadriceps femoris and tendon, as well as cartilage mechanics and morphology. The results show that acupotomy has a protective effect on cartilage by adjusting the mechanical properties of the soft tissues around the knee joint, improving the cartilage stress environment, and delaying cartilage degeneration.

Author Spotlight: Investigating the Mechanism of Action of Acupotomy in Treating Knee Osteoarthritis

In this protocol, a knee osteoarthritis model was prepared using the modified Videman method, and the operation procedures and precautions of acupotomy are detailed. The effectiveness of acupotomy has been demonstrated by testing the mechanical properties of quadriceps femoris and tendon and the mechanical and morphological properties of cartilage.

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department, which seriously reduces the quality of life of ...

An Efficient Modified Method for Treating Wasting Marmoset Syndrome

Modification of the Treatment Methods for Wasting Marmoset Syndrome with Tranexamic Acid and Supportive Measures

Wasting marmoset syndrome (WMS), a serious disease in captive common marmoset (Callithrix jacchus) colonies, is associated with a high mortality rate. The specific cause of WMS is still unclear and there are few effective treatments. Previously, we had reported a tranexamic acid therapy with supportive measures as a useful treatment for WMS. In the present study, we describe the modified method: a combination of 0.1 mL of 5% tranexamic acid subcutaneously five times per week, 2.0 mL of amino acid formulation intravenously three times per week, 5.0 mL of Ringer's lactate with 0.1 mL of a vitamin formulation subcutaneously three times per week, and oral administration of 0.1 mL of an iron formulation five times per week. We also describe how to administer the solution intravenously via the saphenous vein with a tip of restraining the animal, as well as the detailed methods for oral and subcutaneous administration. The modified methods have comparable efficiency to the original WMS treatment method.

Author Spotlight: Developing a Safer and More Efficient Treatment Protocol for Wasting Marmoset Syndrome (WMS)

Here, we describe the modified treatment methods for wasting marmoset syndrome (WMS, also known as inflammatory bowel disease (IBD)-like disease) with tranexamic acid. We also present how to administer the therapeutic agents orally, subcutaneously, and intravenously.

Wasting marmoset syndrome (WMS), a serious disease in captive common marmoset (Callithrix jacchus) colonies, is associated with a high mortality rate. The ...

Combined Intervention Training for Children with Spastic Cerebral Palsy 

Repeated Transcranial Magnetic Stimulation Combined with Action Observation Training in Children with Spastic Cerebral Palsy

This study presents the results of a randomized controlled trial utilizing a 2 x 2 factorial design, comparing the effects of repeated transcranial magnetic stimulation (rTMS) and action observation training (AOT) intervention methods on spasticity, balance function, and motor function in children with spastic cerebral palsy (SCP). The study aimed to investigate whether the combination of the two interventions produces greater improvement than either treatment alone or conventional treatment.
Subject children in this study, in accordance with the random number table, were randomly divided into four groups: conventional group, rTMS group, AOT group, and combined intervention group. All the children in the four groups received conventional rehabilitation treatment, on the basis of which they were given different therapeutic programs of rehabilitation measures. The conventional group had no other treatment while the rTMS group received rTMS, the AOT group received AOT and the combined intervention group was given a combined intervention of rTMS and AOT. They were trained five days per week for 12 weeks. Changes in scores of spasticity, balance function, walking ability, and gross motor function were assessed at the onset of the training program and upon completion of 12 weeks of treatment.
A total of 64 Children with SCP completed the study, and their results were analyzed. The total gross motor function efficiency of 87.50% in the experimental group was significantly higher than that of 25.00% in the conventional group, 62.50% in the rTMS group, and 68.75% in the AOT group. The preliminary results showed that combined intervention of rTMS and AOT could effectively improve the balance function and motor function of children, and the therapeutic effect of the combined intervention was better than that of conventional treatment, rTMS or AOT alone. Finally, clinical efficacy and optimal treatment parameters of the combined intervention were clarified to provide a clinical basis for therapists to conduct lower limb function rehabilitation for children with SCP.

Author Spotlight: Repetitive Transcranial Magnetic Stimulation Combined with Movement Observation in Cerebral Palsy

Children with spastic cerebral palsy (SCP) have limb spasticity, movement disorders, and abnormal posture due to injury to the cerebral cortex motor area, resulting in inability to stand and walk normally. Therefore, alleviating limb spasticity and enhancing gross motor function in children with SCP have become important therapeutic goals.

This study presents the results of a randomized controlled trial utilizing a 2 x 2 factorial design, comparing the effects of repeated transcranial ...

Acupuncture Procedure for Treating Myopia with Dry Eye

Acupoint and Ear Plaster Therapy for Treating Sleep Disorders in AECOPD Patients

Acupoint Application Combined with Ear Plaster Therapy for Treating Sleep Disorders with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a lung disease characterized by persistent airflow limitation, which is not fully reversible and progressive. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) refers to acute changes in respiratory distress, cough, and sputum in COPD patients at baseline levels. Sleep disorders are a very common complication in patients with AECOPD. At present, long-term use of sedative-hypnotics alone has many side effects, such as mental and physical dependence and cognitive impairment. While the efficacy of other special intervention methods is not clear, and the cost is high, there is an urgent need for effective and safe treatment in clinics. Acupoint application and ear plaster therapy are considered the characteristic therapies of traditional Chinese medicine. They have the advantages of small side effects, high safety, and simple procedure. This study will elucidate in detail the specific process and efficacy of the two treatment methods for AECOPD complicated with sleep disorders, including medical devices used, selection of acupoints, procedure, and posttreatment care. This study is intended to provide a new reference for the clinical treatment modality of this type of disease.

Author Spotlight: Traditional Chinese Medicine for Sleep Disorders in Acute COPD &#8212; A Safe, Cost-Effective Approach

The present protocol describes the specific process and efficacy of the acupoint application combined with ear plaster therapy for sleep disorders in a patient with acute exacerbation of chronic obstructive pulmonary disease, including medical devices, selection of acupoints, operating methods, and posttreatment care.