We appreciate the financial support from (1) National Nature Science Foundation (81973877), (2)the Three year Action Plan of Shanghai to Further Accelerate the Inheritance, Innovation and Development of Traditional Chinese Medicine (ZY (2021-2023)-0201-01) , (3) Pudong New Area Health System Pudong Famous Physician Training Plan (PWRzm2020-15), and (4) Chinese Medicine Rehabilitation Service Enhancement Project (Medical 032).

The protocol of this study has been approved by the Human Research Ethics Committee of Longhua Hospital Affiliated with Shanghai University of Traditional Chinese Medicine (Approval Number: 2023-LHXS-030). Before the trial, written informed consent was provided by each patient included in the study. A total of 76 patients with stage I-II frozen shoulder in the rehabilitation department of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine from December 2022 to May 2023, who met the inclusion criteria, were randomly divided into a control group and a treatment group, with 38 cases in each group. The operator must be familiar with the anatomy of the shoulder joint and the specific surgical method.
1. Recruitment of patients
<ol>
	<li>Use the following inclusion criteria to enroll patients in this study: Conform to the diagnostic criteria of frozen shoulder; stage I or II frozen shoulder; regardless of gender, 40-65 years old; VAS score &#8804; 7; without other treatment at the same time.</li>
	<li>Use the following exclusion criteria to not include patients in this study: Patients with blood coagulation dysfunction; diabetic patients with unstable blood sugar control; pregnant pand lactating women; patients with damaged treatment sites or serious infection; Patients with allergies to anesthesia.</li>
</ol>
2. Exercises regime for control group
<ol>
	<li>Subject patients in the control group to a treatment course of functional exercises as described below19.
	<ol>
		<li>Hand wall climbing: Ask the patient to stand facing the wall with both feet open and raising both hands to climb up along the wall. Ask the patient to take the hands to the highest scales with the maximum tolerance and record this for each patient.</li>
		<li>Assisted hand: In a standing position, ask the patient to keep the affected upper limb in the state of backward extension and perform internal rotation to the opposite side by pulling the wrist of the affected upper limb with the healthy upper limb, and then maintain the upward pulling state to the maximum tolerance for the patient.</li>
		<li>Pendulum swings: In standing and bending down position, ask the patient to support the healthy arm of each patient and drop to the affected side and perform the back and forth, left and right, as well as circle movements. Increase the range of motion when the symptoms are improved and draw circles by holding an object which is 1-2 kg (such as water bottles, dumbbells) to increase the intensity of stretching exercises.</li>
	</ol>
	</li>
	<li>Course of functional exercise: Ensure the patients in the control group perform functional exercises every day including wall climbing, assisted hand and the pendulum swings, 30 times/day for 4 weeks. 
	NOTE: The functional exercise must be carried out within the tolerance range; otherwise, it may cause soft tissue strain in the shoulder and lead to deterioration of the condition.</li>
	<li>Follow the principle of - from light to heavy, from small to large, step by step and continuously - during the functional exercise. Ask the patient to avoid long-term shoulder work, heavy lifting, or strenuous activities, though the patient can perform all day-to-day activities during treatment.</li>
</ol>
3. Exercise regime for treatment group
<ol>
	<li>Subject patients in the treatment group to small needle knife therapy with functional exercises.</li>
	<li>Preoperative preparation
	<ol>
		<li>Material preparation (Figure 1): Sterilize disposable medical plastic cup, medical tweezers, absorbent cotton ball, dressing block, a 40 mm x 40 mm disposable sterile small needle knife, marker pen, type II skin disinfectant, 2% lidocaine hydrochloride, sterile water for injection, 10 mL disposable sterile syringe, disposable sterile injection needle, rubber surgical gloves, self-adhesive dressing.</li>
		<li>Patient information check: Check the basic information of each patient (name, age, affected shoulder). Explain the process and advantages of the small needle knife therapy. Make sure that the patients fully understand and relax during the operational procedure.</li>
		<li>Patient preparation: Fully expose the affected shoulder in a sitting position.</li>
		<li>Positioning (Figure 2): Mark the obvious tenderness points of the affected shoulder, such as the coracoid process point (attachment point of the short head of the biceps), lesser tuberosity of greater (attachment point of the subscapular muscle), intertubercular sulcus (attachment point of the long head of the biceps muscle), subacromial bursae (attachment point of the supraspinatus muscle), 2 cm behind the greater tuberosity of humerus (attachment point of the teres minor muscle)20.</li>
		<li>Disinfection: Prepare cotton balls in type II skin disinfectant. Routinely disinfect the skin 3x with gradually reduced diameter starting from 15 cm around the marking point.</li>
	</ol>
	</li>
	<li>Operational procedure (Figure 2)
	<ol>
		<li>Load 5 mL 2% lidocaine plus 5 mL of sterile water into&#160;a 10 mL syringe to prepare a 10 mL 1% lidocaine working solution.&#160;</li>
		<li>Replace the 22G needle with a 25G needle (use thinner needles to ease the pain). Wear the sterile gloves on the left hand and hold the syringe in the right hand.</li>
		<li>Insert the needle into the mark and make sure no blood returns upon aspiration. Perpendicularly inject 1-2 mL of 1% lidocaine working solution at each marked point.</li>
		<li>Small needle knife insertion (Figure 2): Wear sterile gloves in the right hand to hold the small needle knife. Rapidly insert the small needle knife into the lidocaine injection site perpendicularly with a depth of about 1-3 cm. Make sure that the blade of the small needle knife is parallel to the muscle fibers to avoid damage to important blood vessels and nerves.</li>
		<li>Perform the 3-step manipulation of longitudinal incision, stripping and releasing the adhesion7,15. The patient will feel local soreness and pain, and the operator will feel resistance under the knife.</li>
		<li>Withdraw the needle when the operator feels a sense of looseness under the knife.</li>
	</ol>
	</li>
	<li>Postoperative care (Figure 2)
	<ol>
		<li>Press the injection site for 1 min with a dry sterile cotton ball. Cover the operating area with a sterile self-adhesive dressing.</li>
		<li>Assist the patients to dress well. 
		NOTE: Put the medical waste into the medical waste trash can.</li>
		<li>Ask the patient to sit still for about 15 min before leaving the operating room to avoid postoperative discomfort. Advice the patient to keep the self-adhesive dressing dry until it is removed 48 h later to avoid bleeding and infection.</li>
	</ol>
	</li>
	<li>Course of small needle knife therapy21: Subject the patients in the treatment group to small needle knife therapy, once a week with a total of 4 sessions. Carry out the same functional exercises for patients in the treatment group as done for the control group.</li>
</ol>
4. Post-intervention outcome assessments
<ol>
	<li>Evaluation index22,23,24
	<ol>
		<li>Use the visual analogue scores (VAS), the Constant and Murley scores (CMS), and the thickness of CHL under ultrasound to assess the outcome. 
		NOTE: The baseline measurements were performed before and one week after the treatment.</li>
	</ol>
	</li>
	<li>Assessment instruments
	<ol>
		<li>Use the GJJDC01 high-precision joint motion electronic measuring instrument for shoulder joint motion measurement and a portable color ultrasound system (Figure 3).</li>
	</ol>
	</li>
	<li>Assessment instruments operation method (Figure 3)
	<ol>
		<li>Measurement of shoulder range of motion.
		<ol>
			<li>Press ON to turn on the power. Ask the subject to uplift the shoulder to the maximum angle possible. Rotate the measuring ruler and obtain the measured value.</li>
			<li>Set the measuring instrument scale back to 0 and repeat the measurement 2x. Press and hold OFF to turn the power off.</li>
		</ol>
		</li>
		<li>Measurement of the thickness of CHL using an ultrasound.
		<ol>
			<li>Turn ON the ultrasound machine by pressing the Power button. Press the Patient button, click New Patient, and enter the name of the subject.</li>
			<li>Ask the patient to fully expose the affected shoulder in a seated position. Move the shoulder joint of the patient passively to locate the CHL. Align the ultrasound probe with the CHL.</li>
			<li>Press the Freeze button to save the ultrasound image. Press the Caliper button to test CHL thickness. Record the measurement and turn it OFF.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
5. Statistical analysis
<ol>
	<li>Present the continuous variables as mean &#177; standard deviation (SD). Use the independent sample t-test to compare the differences between the two groups. All statistical tests were two-sided, and P&#60;0.05 was considered statistically significant. All analyses were performed using statistical software.</li>
</ol>

Therapeutic Efficacy of Small Needle Knife Therapy in Treating Frozen Shoulder

<ol>
	<li>Abrassart, S., 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='Frozen+shoulder'+is+ill-defined.+How+can+it+be+described+better.">'Frozen shoulder' is ill-defined. How can it be described better.</a> EFORT Open Rev. 5 (5), 273-279 (2020).</li><li>Ramirez, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adhesive+capsulitis:+Diagnosis+and+management.">Adhesive capsulitis: Diagnosis and management.</a> Am Fam Physician. 99 (5), 297-300 (2019).</li><li>Hsu, J. E., Anakwenze, O. A., Warrender, W. J., Abboud, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+review+of+adhesive+capsulitis.">Current review of adhesive capsulitis.</a> J Shoulder Elbow Surg. 20 (3), 502-514 (2011).</li><li>Hand, C., Clipsham, K., Rees, J. L., Carr, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+outcome+of+frozen+shoulder.">Long-term outcome of frozen shoulder.</a> J Shoulder Elbow Surg. 17 (2), 231-236 (2008).</li><li>White, D., Choi, H., Peloquin, C., Zhu, Y., Zhang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Secular+trend+of+adhesive+capsulitis.">Secular trend of adhesive capsulitis.</a> Arthritis Care Res. 63 (11), 1571-1575 (2011).</li><li>Qin, X., 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=Traditional+Chinese+Medicine+for+Frozen+shoulder:+An+evidence-based+guideline.">Traditional Chinese Medicine for Frozen shoulder: An evidence-based guideline.</a> J Evid Based Med. 16, 246-258 (2023).</li><li>Zhu, J., 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=The+effects+of+small+needle+knife+therapy+on+pain+and+mobility+from+knee+osteoarthritis:+a+pilot+randomized-controlled+study.">The effects of small needle knife therapy on pain and mobility from knee osteoarthritis: a pilot randomized-controlled study.</a> Clin Rehabil. 34 (12), 1497-1505 (2020).</li><li>Deng, D. W., 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=Clinical+effect+of+small+needle+knife+on+frozen+shoulder.">Clinical effect of small needle knife on frozen shoulder.</a> Massage Rehabil Med. 13 (13), 15-20 (2022).</li><li>Liu, 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=Advances+in+the+treatment+of+frozen+shoulder+with+small+needle+knife.">Advances in the treatment of frozen shoulder with small needle knife.</a> Rheumatol Arthritis. 11 (12), 67-70 (2022).</li><li>Ruan, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+efficacy+and+safety+analysis+of+small+needle+knife+combined+with+functional+exercise+in+the+treatment+of+frozen+shoulder.">Clinical efficacy and safety analysis of small needle knife combined with functional exercise in the treatment of frozen shoulder.</a> Chinese J Med Sci. 10 (9), 39-41 (2019).</li><li>Kwon, C. Y., Yoon, S. H., Lee, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+effectiveness+and+safety+of+acupotomy:+An+overview+of+systematic+reviews.">Clinical effectiveness and safety of acupotomy: An overview of systematic reviews.</a> Complement Ther Clin Pract. 36, 142-152 (2019).</li><li>Liu, F. S., Jin, X. F., Guo, C. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+review+of+acupuncture+versus+small+needle+knife+for+frozen+shoulder.">Systematic review of acupuncture versus small needle knife for frozen shoulder.</a> Chinese J Traditional Chinese Med. 27 (3), 582-585 (2021).</li><li>Yang, W. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+review+on+curative+effect+of+small-needle-knife+therapy+combined+with+manipulation+for+frozen+shoulder.">Systematic review on curative effect of small-needle-knife therapy combined with manipulation for frozen shoulder.</a> Chinese J Info Traditional Chinese Med. (12), 94-98 (2018).</li><li>He, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=On+the+role+and+relationship+between+&amp;#34;needle&amp;#34;+and+&amp;#34;knife&amp;#34;+in+small+needle+knife+therapy.">On the role and relationship between &amp;#34;needle&amp;#34; and &amp;#34;knife&amp;#34; in small needle knife therapy.</a> Clin J Acupuncture Moxibustion. (9), 28-29 (2000).</li><li>Hu, Z. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Clinical Practice of practical small needle knife. , (2018).</li><li>Wen, H. W., Zeng, W. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bibliometrics+and+knowledge+graph+analysis+of+small+needle+knife.">Bibliometrics and knowledge graph analysis of small needle knife.</a> Chinese J Lib Info Traditional Chinese Med. 45 (6), 13-17 (2021).</li><li>Qin, X., 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=Outcomes+of+visualized+puncture+needle+and+small+needle+knife+therapy+in+primary+frozen+shoulder+based+on+multimodal+ultrasound+imaging.">Outcomes of visualized puncture needle and small needle knife therapy in primary frozen shoulder based on multimodal ultrasound imaging.</a> J Healthc Eng. 2022, 1076112 (2022).</li><li>Zeng, X., Ding, Z. H., Fu, L. Q., Liu, S. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Research+progress+of+ultrasound+small+needle+knife+visualization.">Research progress of ultrasound small needle knife visualization.</a> J Acupuncture Res. 46 (6), 546-548 (2019).</li><li>Mertens, M. G., Meert, L., Struyf, F., Schwank, A., Meeus, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise+therapy+is+effective+for+improvement+in+range+of+motion,+function,+and+pain+in+patients+with+frozen+shoulder:+A+systematic+review+and+meta-analysis.">Exercise therapy is effective for improvement in range of motion, function, and pain in patients with frozen shoulder: A systematic review and meta-analysis.</a> Arch Phys Med Rehabil. 103 (5), 998-1012 (2022).</li><li>Xu, W. S., Liu, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+observation+of+&amp;#34;C&amp;#34;+shape+release+by+small+needle+knife+in+treatment+of+frozen+shoulder.">Clinical observation of &amp;#34;C&amp;#34; shape release by small needle knife in treatment of frozen shoulder.</a> J Liaoning Uni Traditional Chinese Med. 21 (9), 185-188 (2019).</li><li>Liang, C. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Basic+research+on+a+recommended+program+of+clinical+practice+guidelines+for+small+needle+knife+treatment+of+frozen+shoulder.">Basic research on a recommended program of clinical practice guidelines for small needle knife treatment of frozen shoulder.</a> Beijing University of Chinese Medicine. , (2012).</li><li>Tian, Z. R., Yao, M., Wang, Y. J., Cui, X. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+application+of+Constant-Murley+shoulder+joint+Rating+scale+in+Chinese.">Development and application of Constant-Murley shoulder joint Rating scale in Chinese.</a> Chinese Med Bone Sett. 31 (5), 20-25 (2019).</li><li>Yin, 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=Application+of+visual+diagnosis+and+treatment+technique+(ultrasound)+in+diagnosis+and+treatment+of+frozen+shoulder+and+evaluation+of+curative+effect.">Application of visual diagnosis and treatment technique (ultrasound) in diagnosis and treatment of frozen shoulder and evaluation of curative effect.</a> Chinese J Med Ultrasound. 16 (11), 810-814 (2019).</li><li>Fan, Z. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+measurement+of+coracohumeral+ligament+thickness+in+diagnosis+and+evaluation+of+the+curative+effect+of+frozen+shoulder.">The role of measurement of coracohumeral ligament thickness in diagnosis and evaluation of the curative effect of frozen shoulder.</a> Soochow University. , (2018).</li><li>Reeves, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+natural+history+of+the+frozen+shoulder+syndrome.">The natural history of the frozen shoulder syndrome.</a> Scand J Rheumatol. 4 (4), 193-196 (1975).</li><li>Xu, Y., Bonar, F., Murrell, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhanced+expression+of+neuronal+proteins+in+idiopathic+frozen+shoulder.">Enhanced expression of neuronal proteins in idiopathic frozen shoulder.</a> J Shoulder Elbow Surg. 21 (10), 1391-1397 (2012).</li><li>Rodeo, S. A., Hannafin, J. A., Tom, J., Warren, R. F., Wickiewicz, T. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immunolocalization+of+cytokines+and+their+receptors+in+adhesive+capsulitis+of+the+shoulder.">Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder.</a> J Orthop Res. 15 (3), 427-436 (1997).</li><li>Green, H. D., 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+genome-wide+association+study+identifies+5+loci+associated+with+frozen+shoulder+and+implicates+diabetes+as+a+causal+risk+factor.">A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.</a> PLoS Genet. 17 (6), e1009577 (2021).</li><li>Hand, G. C., Athanasou, N. A., Matthews, T., Carr, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pathology+of+frozen+shoulder.">The pathology of frozen shoulder.</a> J Bone Joint Surg Br. 89 (7), 928-932 (2007).</li><li>Lho, Y. M., 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=Inflammatory+cytokines+are+overexpressed+in+the+subacromial+bursa+of+frozen+shoulder.">Inflammatory cytokines are overexpressed in the subacromial bursa of frozen shoulder.</a> J Shoulder Elbow Surg. 22 (5), 666-672 (2013).</li><li>Han, Y. L., Sun, W. Q., Huo, S. F., Xu, Z. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+therapeutic+effect+and+mechanism+of+small+needle+knife+in+the+treatment+of+patients+with+cold-dampness-blocking+frozen+shoulder.">Recent therapeutic effect and mechanism of small needle knife in the treatment of patients with cold-dampness-blocking frozen shoulder.</a> World of Chinese Medicine. 13 (5), 1254-1257 (2018).</li><li>Zhou, D., 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+small+needle+knife+therapy+on+expression+of+IL-1&#946;,+TNF-&#945;,+and+ASIC1+in+local+tissue+of+rabbits+with+frozen+shoulder.">Effect of small needle knife therapy on expression of IL-1&#946;, TNF-&#945;, and ASIC1 in local tissue of rabbits with frozen shoulder.</a> Shanghai J Acupuncture Moxibustion. 40 (6), 762-768 (2021).</li><li>Zhang, Z. F. <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+small+needle+knife+and+local+closure+on+pain+mediators+and+inflammatory+factors+in+patients+with+frozen+shoulder.">Effect of small needle knife and local closure on pain mediators and inflammatory factors in patients with frozen shoulder.</a> Clin Res Chinese Med. 10 (8), 82-84 (2018).</li><li>Bunker, T. D., Reilly, J., Baird, K. S., Hamblen, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+of+growth+factors,+cytokines+and+matrix+metalloproteinases+in+frozen+shoulder.">Expression of growth factors, cytokines and matrix metalloproteinases in frozen shoulder.</a> J Bone Joint Surg Br. 82 (5), 768-773 (2000).</li><li>Millar, N. 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=Frozen+shoulder.">Frozen shoulder.</a> Nat Rev Dis Primers. 8 (1), 59 (2022).</li><li>Li, H. Y., Chen, S. Y., Zhai, W. T., Chen, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+of+TGF-&#946;+and+MMPs+in+capsula+tissue+of+frozen+shoulder+patients.">Expression of TGF-&#946; and MMPs in capsula tissue of frozen shoulder patients.</a> J Shanghai Jiaotong Uni. 29 (11), 1363-1366 (2009).</li><li>Cher, J. Z. B., 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=Alarmins+in+Frozen+Shoulder:+A+Molecular+Association+Between+Inflammation+and+Pain.">Alarmins in Frozen Shoulder: A Molecular Association Between Inflammation and Pain.</a> Am J Sports Med. 46 (3), 671-678 (2018).</li><li>Wang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+study+on+the+treatment+of+frozen+shoulder+in+rats+with+&amp;#34;C&amp;#34;+shaped+small+needle+knife.">Experimental study on the treatment of frozen shoulder in rats with &amp;#34;C&amp;#34; shaped small needle knife.</a> Hubei Uni Chinese Med. , (2020).</li><li>Bai, Y., Chen, B., Qin, Y. N., Du, Y. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thoughts+on+constructing+the+core+outcome+index+set+of+clinical+research+on+frozen+shoulder.">Thoughts on constructing the core outcome index set of clinical research on frozen shoulder.</a> Chinese Med J. 36 (1), 69-73 (2019).</li><li>Buchbinder, 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=A+Preliminary+Core+Domain+Set+for+Clinical+Trials+of+Shoulder+Disorders:+A+Report+from+the+OMERACT+2016+Shoulder+Core+Outcome+Set+Special+Interest+Group.">A Preliminary Core Domain Set for Clinical Trials of Shoulder Disorders: A Report from the OMERACT 2016 Shoulder Core Outcome Set Special Interest Group.</a> J Rheumatol. 44 (12), 1880-1883 (2017).</li><li>Fan, Z. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+measurement+of+coracohumeral+ligament+thickness+in+diagnosis+and+evaluation+of+curative+effect+of+frozen+shoulder.">The role of measurement of coracohumeral ligament thickness in diagnosis and evaluation of curative effect of frozen shoulder.</a> Soochow University. , (2018).</li><li>Xiu, Z. B., 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=Clinical+guidelines+of+small+needle+knife+for+knee+osteoarthritis.">Clinical guidelines of small needle knife for knee osteoarthritis.</a> J Rehabil. 33 (3), 193-201 (2019).</li></ol>

The authors report no conflicts of interest.

In this study, we found that the small needle knife therapy significantly relieved the pain symptoms, improved the shoulder joint function, reduced the thickness of CHL, and improved the quality of life in stage I-II frozen shoulder patients. The small needle knife therapy had exact effect on frozen shoulder. However, the operation site is controversial. Due to the different knowledge backgrounds, many operation sites can be selected to treat frozen shoulders with small needle knife. The main operation sites are tender p...

Frozen shoulder is a disease characterized by pain and limitation of active and passive shoulder movement, which causes great inconvenience to the work and life of patients1. The global incidence of frozen shoulder is 2%-5%2,3 and higher in females than in males, showing a certain genetic tendency4. The majority of frozen shoulder patients are 40-60 years old5. Moreover, the frozen shoulder brings about a heavy social burden due to the longer recovery cycle and the absence of established treatment consensus in the clinic practice.
The main treatment methods for frozen shoulders include oral or external use of herbal medicine, acupuncture, massage, functional exercise, and so on6; however, the compliance of the patients is poor due to the multiple treatment frequency and longer time-consuming, and cannot meet the urgent necessities of patients to improve pain and functional limitations. Therefore, it is urgently needed to identify more effective therapeutics in the clinical management of frozen shoulder patients.
Small needle knife therapy is a special and effective external treatment of traditional Chinese medicine, which has arisen rapidly in the field of traditional Chinese medicine in recent decades7. It has the advantages of quick effect, definite curative effect, and high repeatability. Moreover, the operation instrument is cheap and easy to obtain, the operation process is simple, and the method is not limited by the environment and condition. The normal work and life of patients are not affected after the small needle knife therapy since the micro-incision will be recovered quickly without damage to the body, causing infection, or other side effects8,9,10,11. Systematic reviews showed that the efficacy of small needle knife on frozen shoulder was significantly superior to acupuncture, massage, and oral Chinese medicine12,13. Modern studies show that the mechanism of small needle knife treatment of frozen shoulder is to dredge the meridians and collaterals, promote the circulation of qi and blood, cut and strip the lesion tissue, remove adhesion, promote tissue repair, and restore the dynamic balance of the human body14,15.
The protocol presented here demonstrates the operation of small needle knife in treating frozen shoulders including patient management, material preparation, positioning, operation, and postoperative care. The purpose of this protocol is to relieve the pain and functional limitations and improve the living ability of patients with frozen shoulders.
With the development of small needle knife therapy, its application has been extended from the treatment of neck, shoulder, waist, leg pain, and other muscle and bone diseases to internal medicine, surgery, gynecology, pediatrics, and other diseases, playing an increasingly important role in the field of rehabilitation medicine16. In recent years, the small needle knife shows a more accurate, scientific, and safe therapeutic efficacy due to the application of ultrasound-guided small needle knife visualization therapy, whose development has entered a new stage17,18.

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			<td>Disposable sterile injection needle</td>
			<td>Shanghai Mishava Medical Industry Co., Ltd</td>
			<td>601900973</td>
			<td>Type specification:0.5 x 38 RWLB</td>
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			<td>Disposable sterile small needle-knife</td>
			<td>Wujiang Yunlong Medical equipment Co., Ltd</td>
			<td>PR-4040</td>
			<td>Type specification:40 mm x 40 mm&#160;</td>
		</tr>
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			<td>Disposable sterile syringe</td>
			<td>Shandong Weigo Group Medical polymer Products Co., Ltd</td>
			<td>601909174</td>
			<td>Type specification:10 mL</td>
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			<td>Lidocaine hydrochloride</td>
			<td>Shanghai Hefeng Pharmaceutical Co., Ltd</td>
			<td>6904996104121</td>
			<td>Type specification:5 mL</td>
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			<td>Marker pen</td>
			<td>Zebra Trading (Shenzhen) Co., Ltd</td>
			<td>4901681518111</td>
			<td>Type specification:1.0 mm/0.5 mm</td>
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			<td>Sterile absorbent cotton ball</td>
			<td>Shanghai Honglong Medical Supplies Equipment Co., Ltd</td>
			<td>601905637</td>
			<td>Type specification:0.3&#160; 25 g</td>
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			<td>Sterile disposable medical plastic cup</td>
			<td>Shanghai Honglong Medical Supplies Equipment Co., Ltd</td>
			<td>709008633</td>
			<td>Type specification:Waist-shaped disc</td>
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			<td>Sterile dressing block</td>
			<td>Ningbo Haishu Shenyuan Medical Materials Co.,&#160; Ltd</td>
			<td>601909470</td>
			<td>Type specification:7.5 cm x 7.5 cm x 8 floors</td>
		</tr>
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			<td>Sterile medical tweezers</td>
			<td>Shanghai Honglong Medical Supplies Equipment Co.,Ltd</td>
			<td>603917444</td>
			<td>Type specification:Small size</td>
		</tr>
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			<td>Sterile rubber surgical gloves</td>
			<td>Guilin Hengbao health protection Co.,&#160; Ltd</td>
			<td>6971787071320</td>
			<td>Type specification:6.5</td>
		</tr>
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			<td>Sterile self-adhesive dressing</td>
			<td>Shanghai ISO Medical Products Co., Ltd</td>
			<td>601909414</td>
			<td>Type specification:10 cm x 15 cm</td>
		</tr>
		<tr>
			<td>Sterile water for injection</td>
			<td>Shanghai Xinyi Jinzhu Pharmaceutical Co., Ltd</td>
			<td>6938493300953</td>
			<td>Type specification:5 mL</td>
		</tr>
		<tr>
			<td>Type II skin disinfectant</td>
			<td>Shanghai Likang Disinfection high-tech Co., Ltd</td>
			<td>6909157000359</td>
			<td>Type specification:500 mL/ bottle</td>
		</tr>
		<tr>
			<td>Ultrasound</td>
			<td>Suzhou Daer Medical Equipment Co., Ltd</td>
			<td>100018857</td>
			<td>uSmart3300 portable color ultrasound system</td>
		</tr>
	</tbody>
</table>

clinical efficacy of small needle knife therapy on stage i-ii frozen shoulder

Frozen shoulder is a kind of aseptic inflammatory disease of the shoulder caused by strain, trauma, and other reasons, resulting in shoulder joint pain and limited function. The protocol presented here demonstrates the operation of a small needle knife in treating frozen shoulders, including patient management, material preparation, positioning, operation, and postoperative care. The purpose of this protocol is to relieve the pain and functional limitations and improve the living ability of patients with frozen shoulders. In our study, 76 stage I-II frozen shoulder patients who met the inclusion criteria were randomly divided into a control group and a treatment group (n=38). Patients in the control group received functional exercise, while the treatment group received small needle knife therapy with functional exercise. The visual analogue scores (VAS), the Constant and Murley scores (CMS), and the thickness of the coracohumeral ligament (CHL) under ultrasound were evaluated. After small needle knife therapy, the VAS score was significantly lower in the treatment group (5.11 &plusmn; 0.89) than in the control group (5.49 &plusmn; 0.65; t=-2.065, p&lt;0.05); the CMS score was significantly higher in the treatment group (64.72 &plusmn; 4.78) than in the control group (60.97 &plusmn; 6.00; t=2.947, p&lt;0.05); the CHL thickness was significantly decreased in the treatment group (2.38 &plusmn; 0.36) than in the control group (2.57 &plusmn; 0.42; t=-2.117, p&lt;0.05). These results indicate that the small needle knife significantly relieved the pain symptoms, improved the shoulder function, reduced the CHL thickness, and improved the quality of life and, therefore, had significant therapeutic efficacy in stage I-II frozen shoulder patients.

In the control group, 1 patient received other treatment (intra-articular steroid injection) due to aggravation of pain, so the trial was terminated, and the remaining 37 patients in the control group were included in the final statistical analysis. For 2 patients in the treatment group CHL could not be detected under ultrasound, so the test was eliminated, and the remaining 36 patients in the treatment group entered the final statistical analysis.
Baseline characteristics<br ...

Watch this Scientific Journal Video about Treating Frozen Shoulder with Small Needle Knife Therapy at JoVE.com

Author Spotlight: Treating Frozen Shoulder with Small Needle Knife Therapy 

The protocol presented here describes the detailed operation method and proves the effectiveness of a small needle knife in the treatment of frozen shoulders.

Clinical Efficacy of Small Needle Knife Therapy on Stage I-II Frozen Shoulder

Frozen shoulder is a kind of aseptic inflammatory disease of the shoulder caused by strain, trauma, and other reasons, resulting in shoulder joint pain ...

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1.2K Views.  Shanghai University of Traditional Chinese Medicine. The protocol presented here describes the detailed operation method and proves the effectiveness of a small needle knife in the treatment of frozen shoulders.

Video: Author Spotlight: Treating Frozen Shoulder with Small Needle Knife Therapy 

Reverse Total Shoulder Arthroplasty

Reverse total shoulder arthroplasty was initially approved for use in rotator cuff arthropathy and well as chronic pseudoparalysis without arthritis in patients who were not appropriate for tendon transfer reconstructions. Traditional surgical options for these patients were limited and functional results were sub-optimal and at times catastrophic. The use of reverse shoulder arthroplasty has been found to effectively restore these patients function and relieve symptoms associated with their disease. The procedure can be done through two approaches, the deltopectoral or the superolateral. Complication rates associated with the use of the prosthesis have ranged from 8-60% with more recent reports trending lower as experienced is gained. Salvage options for a failed reverse shoulder prosthesis are limited and often have significant associated disability. Indications for the use of this prosthesis continue to be evaluated including its use for revision arthroplasty, proximal humeral fracture and tumor. Careful patient selection is essential because of the significant risks associated with the procedure.

Reverse total shoulder arthroplasty is indicated for the treatment of conditions that cannot be treated with conventional arthroplasty or other procedures. These primarily include degenerative and incapacitating conditions with irreparable rotator cuff and loss of the normal biomechanical coupling of the shoulder.

Reverse total shoulder arthroplasty was initially approved for use in rotator cuff arthropathy and well as chronic pseudoparalysis without arthritis in ...

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

In recent years, there has been the difficulty in finding more effective therapies against cancer with less systemic side effects. Therefore Photodynamic Therapy is a novel approach for a more tumor selective treatment.
Photodynamic Therapy (PDT) that makes use of a nontoxic photosensitizer (PS), which, upon activation with light of a specific wavelength in the presence of oxygen, generates oxygen radicals that elicit a cytotoxic response1. Despite its approval almost twenty years ago by the FDA, PDT is nowadays only used to treat a limited number of cancer types (skin, bladder) and nononcological diseases (psoriasis, actinic keratosis)2.
The major advantage of the use of PDT is the ability to perform a local treatment, which prevents systemic side effects. Moreover, it allows the treatment of tumors at delicate sites (e.g. around nerves or blood vessels). Here, an intraoperative application of PDT is considered in osteosarcoma (OS), a tumor of the bone, to target primary tumor satellites left behind in tumor surrounding tissue after surgical tumor resection. The treatment aims at decreasing the number of recurrences and at reducing the risk for (postoperative) metastasis.
In the present study, we present in vitro PDT procedures to establish the optimal PDT settings for effective treatment of widely used OS cell lines that are used to reproduce the human disease in well established intratibial OS mouse models. The uptake of the PS mTHPC was examined with a spectrophotometer and phototoxicity was provoked with laser light excitation of mTHPC at 652 nm to induce cell death assessed with a WST-1 assay and by the counting of surviving cells. The established techniques enable us to define the optimal PDT settings for future studies in animal models. They are an easy and quick tool for the evaluation of the efficacy of PDT in vitro before an application in vivo.

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

The protocol reported here allows the evaluation of the efficacy of photodynamic therapy (PDT) in cell lines and the optimization of the PDT settings before applying the therapy in animal models.

In recent years, there has been the difficulty in finding more effective therapies against cancer with less systemic side effects. Therefore Photodynamic ...

Preparation and Respirometric Assessment of Mitochondria Isolated from Skeletal Muscle Tissue Obtained by Percutaneous Needle Biopsy

Respirometric profiling of isolated mitochondria is commonly used to investigate electron transport chain function. We describe a method for obtaining samples of human Vastus lateralis, isolating mitochondria from minimal amounts of skeletal muscle tissue, and plate based respirometric profiling using an extracellular flux (XF) analyzer. Comparison of respirometric profiles obtained using 1.0, 2.5 and 5.0 &#956;g of mitochondria indicate that 1.0 &#956;g is sufficient to measure respiration and that 5.0 &#956;g provides most consistent results based on comparison of standard errors. Western blot analysis of isolated mitochondria for mitochondrial marker COX IV and non-mitochondrial tissue marker GAPDH indicate that there is limited non-mitochondrial contamination using this protocol. The ability to study mitochondrial respirometry in as little as 20 mg of muscle tissue allows users to utilize individual biopsies for multiple study endpoints in clinical research projects.

Methods for biopsy of Vastus lateralis, preparation of purified mitochondria, and respirometric profiling are described. The use of small muscle volume makes this technique suitable for clinical research applications.

Respirometric profiling of isolated mitochondria is commonly used to investigate electron transport chain function. We describe a method for obtaining ...

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

Limited evidence exists to precisely estimate efficacy and safety differences between parenteral nutrition (PN) prepared using olive-oil-based three-chamber bags (3CBs) and soybean-oil-based compounded bags (CoBs) in hospitalized adult patients. We designed a multicenter, randomized, prospective, open-label, noninferiority protocol to compare the efficacy, safety, and distribution of olive-oil-based 3CBs and soybean-oil-based CoB formulations in adult Chinese patients requiring PN during surgical intervention. Subjects were randomized to receive either one of the study treatments using an interactive voice or web-based recognition system in accordance with the randomization code. Randomization was further stratified based on the study site and surgical category. Both treatment groups received similar amounts of calories and protein. In addition, the two study treatments contained a similar composition of the amino-acid component. The only difference between the two PN formulations was the lipid constitution. The duration of administration of study treatments was a minimum of 5 days up to a maximum of 14 days after the surgical procedure. The primary efficacy endpoint was serum prealbumin levels on day 5 of the study. Noninferiority was proved if the anti-log of the lower bound of the 95% confidence interval (CI) of the treatment difference was at least 0.80. Other efficacy measures included treatment preparation time; duration to achieve tolerability of oral nutrition; associated infectious complications; length of hospitalization; and laboratory assessment of markers of nutrition, inflammation, metabolism, and oxidative stress. A total of 458 patients were enrolled in the study. The results showed that olive-oil-based 3CBs were non-inferior to soybean-based CoBs, besides being well tolerated. The infection rate was found to be significantly lower in the olive-oil-based 3CB group. Thus, this study may be used as a reference for future research on lipid emulsion and 3CBs.

Here, we present a protocol for a study comparing the efficacy, safety, and delivery of olive-oil-based 3CB and soybean-oil-based CoB formulations in adults requiring parenteral nutrition. The results revealed that olive-oil-based 3CBs is non-inferior and well tolerated compared to soybean formulations.

Limited evidence exists to precisely estimate efficacy and safety differences between parenteral nutrition (PN) prepared using olive-oil-based ...

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

The fundamentals of radiation planning and delivery for proton therapy using prostate cancer as a model are presented. The application of these principles to other selected disease sites highlights how proton radiotherapy may enhance clinical outcomes for cancer patients.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of ...

A Pre-clinical Rat Model for the Study of Ischemia-reperfusion Injury in Reconstructive Microsurgery

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many areas of biomedical research due to its cost-effectiveness and its translation to humans. This protocol describes a method to create a preclinical free skin flap model in rats with ischemia-reperfusion injury. The described 3 cm x 6 cm rat free skin flap model is easily obtained after the placement of several vascular ligatures and the section of the vascular pedicle. Then, 8 h after the ischemic insult and completion of the microsurgical anastomosis, the free skin flap develops the tissue damage. These ischemia-reperfusion injury-related damages can be studied in this model, making it a suitable model for evaluating therapeutic agents to address this pathophysiological process. Furthermore, two main monitoring techniques are described in the protocol for the assessment of this animal model: transit-time ultrasound technology and laser speckle contrast analysis.

Here, we describe a pre-clinical animal model for studying the pathophysiology of ischemia-reperfusion injury in reconstructive microsurgery. This free skin flap model based on the superficial caudal epigastric vessels in the rat may also allow for the evaluation of different therapies and compounds to counteract ischemia-reperfusion injury-related damage.

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many ...

Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart

Coronary artery disease is one of the significant causes of mortality and morbidity worldwide. Despite the progression of current therapeutics, a considerable proportion of coronary artery disease patients remain symptomatic. Gene therapy-mediated therapeutic angiogenesis offers a novel therapeutic method for improving myocardial perfusion and relieving symptoms. Gene therapy with different angiogenic factors has been studied in few clinical trials. Due to the novelty of the method, the progress of myocardial gene therapy is a continuous path from bench to bedside. Therefore, large animal models are needed for evaluating the safety and efficacy. The more the large animal model identifies the original disease and the endpoints used in clinics, the more predictable outcomes are from clinical trials. Here, we introduce a large animal model for evaluating the efficacy of the gene therapy in the ischemic porcine heart. We use clinically relevant imaging methods such as ultrasound imaging and 15H2O-PET. For targeting the gene transfers into the desired area, electroanatomical mapping is used. The aim of this method is: (1) to mimic chronic coronary artery disease, (2) to induce therapeutic angiogenesis at hypoxic areas of the heart, and (3) to evaluate the safety and efficacy of the gene therapy by using relevant endpoints.

Myocardial gene therapy for ischemic heart disease holds great promise for future therapeutics. Here, we introduce a large animal model for evaluating the efficacy of gene therapy in the ischemic heart.

Coronary artery disease is one of the significant causes of mortality and morbidity worldwide. Despite the progression of current therapeutics, a ...

Subconjunctival Administration of Adeno-associated Virus Vectors in Small Animal Models

Ocular diseases include a wide range of inherited genetic and acquired disorders that are appealing targets for local drug delivery due to their relative ease of accessibility via multiple administration routes. Subconjunctival (SCJ) injections offer advantages over other intraocular administration routes as they are simple, safe, and usually performed in an outpatient setting. SCJ injections in small animals usually require the assistance of an operating microscope due to the size of the eye. Previous work has demonstrated that SCJ injection of specific adeno-associated virus (AAV) serotypes is a valid gene delivery strategy for targeted transduction of the ocular surface, eye muscle, cornea, and optic nerve, providing a potential approach for the treatment of many ocular diseases.
Herein, a detailed protocol is presented for SCJ injections in a mouse model using an injection system consisting of a programmable infusion/withdrawal syringe pump (which allows for consistent and precise injection speed and pressure) and a gastight removable syringe coupled with microinjection needles. The injection system is also adaptable for other intraocular administration routes such as intrastromal, intracameral, intravitreal, and subretinal injections in small animals. Although the delivery of adeno-associated viral vectors for ocular gene therapy studies is described, the protocol herein can also be adapted for a variety of ophthalmic solutions in small animal models. The key practical steps in the administration route, setup for the injection platform, preparation of the injection, and tips from direct experience will be discussed in detail. In addition, common validation techniques for AAV delivery confirmation to the desired tissues will also be briefly discussed.

In this manuscript, subconjunctival injection is demonstrated as a valid vector delivery method for ocular tissues in mice using an injection system consisting of an infusion/withdrawal syringe pump and a gastight removable syringe coupled with microinjection needles. This injection system is also adaptable for other intraocular administration routes.

Ocular diseases include a wide range of inherited genetic and acquired disorders that are appealing targets for local drug delivery due to their relative ...

Clinical Application of 24 G Cannula Needle and 3-0 Polypropylene Suture in Vas Deferens Exploration

The goal of this article is to present the application of a 24 G cannula and 3-0 polypropylene suture as a simple method for the exploration of the vas deferens. During the exploration of the vas deferens, a 24 G cannula needle was used to puncture it. The fluid in the smear confirmed the presence of sperm, to determine whether or not there was concomitant obstruction at the junction of the epididymis and the vas deferens. Then, a 3-0 polypropylene suture (this suture specification has the advantages of a smooth surface, robust quality, and can be passed through a 24 G cannula needle) was passed through the cannula needle to probe the location of the obstructed site. With this technique, exploration of the vas deferens could be more targeted and accurate.

This protocol presents the clinical application of a 24 G cannula and 3-0 polypropylene suture as a simple and effective method for the exploration of the vas deferens.

The goal of this article is to present the application of a 24 G cannula and 3-0 polypropylene suture as a simple method for the exploration of the vas ...

Improving FSN Therapy in the Rat Model&#58; Minimizing Discomfort and Maximizing Efficiency

Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the mechanisms of action are still not fully understood. During FSN treatment, the FSN needle is inserted and retained in the subcutaneous tissues for a long duration with a swaying movement. However, challenges arise from maintaining a posture while manipulating FSN in animal models (e.g., rats) for researchers. Uncomfortable treatment can lead to fear and resistance to FSN needles, increasing the risk of injury and may even affect research data. Anesthesia may also affect the study results too. Hence, there is a need for strategies in FSN therapy on animals that minimize injury during the intervention. This study employs a chronic constriction injury model in Sprague-Dawley rats to induce neuropathic pain. This model replicates the pain induced by nerve injury observed in humans through surgical constriction of a peripheral nerve, mimicking the compression or entrapment seen in conditions such as nerve compression syndromes and peripheral neuropathies. We introduce an appropriate manipulation for easily inserting an FSN needle into the subcutaneous layer of the animal&#39;s body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat&#39;s discomfort prevents the rat from being tense, which causes the muscle to contract and hinder the entry of the needle and improves the study efficiency.

Author Spotlight: Unveiling the Therapeutic Effects of FSN Treatment &#8211; Bridging Research and Clinical Applications in Neuropathic Pain

We present a protocol for using Fu's subcutaneous needling in a chronic constriction injury model to induce sciatic nerve pain in rats.

Fu&#39;s subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the ...