Fu's subcutaneous needling promotes axonal regeneration and remyelination by inhibiting inflammation and endoplasmic reticulum stress.

Fu's subcutaneous needling (FSN) is a traditional Chinese acupuncture procedure used to treat pain-related neurological disorders. Moreover, the regulation of inflammatory cytokines may provide a favorable environment for peripheral nerve regeneration. In light of this, FSN may be an important novel therapeutic strategy to alleviate pain associated with peripheral neuropathy; however, the underlying molecular mechanisms remain unclear. This study revealed that patients who had osteoarthritis with peripheral neuropathic pain significantly recovered after 1 to 2 weeks of FSN treatment according to the visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne index, walking speed, and passive range of motion. Similarly, we demonstrated that FSN treatment in an animal model of chronic constriction injury (CCI) significantly improved sciatic nerve pain using paw withdrawal thresholds, sciatic functional index scores, and compound muscle action potential amplitude tests. In addition, transmission electron microscopy images of sciatic nerve tissue showed that FSN effectively reduced axonal swelling, abnormal myelin sheaths, and the number of organelle vacuoles in CCI-induced animals. Mechanistically, RNA sequencing and gene set enrichment analysis revealed significantly reduced inflammatory pathways, neurotransmitters, and endoplasmic reticulum stress pathways and increased nerve regeneration factors in the FSN+CCI group, compared with that in the CCI group. Finally, immunohistochemistry, immunoblotting and enzyme-linked immunosorbent assay showed similar results in the dorsal root ganglia and sciatic nerve. Our findings suggest that FSN can effectively ameliorate peripheral neuropathic pain by regulate inflammation and endoplasmic reticulum stress, thereby determine its beneficial application in patients with peripheral nerve injuries.

Identification of cuproptosis-related gene clusters and immune cell infiltration in major burns based on machine learning models and experimental validation.

Introduction: Burns are a global public health problem. Major burns can stimulate the body to enter a stress state, thereby increasing the risk of infection and adversely affecting the patient's prognosis. Recently, it has been discovered that cuproptosis, a form of cell death, is associated with various diseases. Our research aims to explore the molecular clusters associated with cuproptosis in major burns and construct predictive models. Methods: We analyzed the expression and immune infiltration characteristics of cuproptosis-related factors in major burn based on the GSE37069 dataset. Using 553 samples from major burn patients, we explored the molecular clusters based on cuproptosis-related genes and their associated immune cell infiltrates. The WGCNA was utilized to identify cluster-specific genes. Subsequently, the performance of different machine learning models was compared to select the optimal model. The effectiveness of the predictive model was validated using Nomogram, calibration curves, decision curves, and an external dataset. Finally, five core genes related to cuproptosis and major burn have been was validated using RT-qPCR. Results: In both major burn and normal samples, we determined the cuproptosis-related genes associated with major burns through WGCNA analysis. Through immune infiltrate profiling analysis, we found significant immune differences between different clusters. When K=2, the clustering number is the most stable. GSVA analysis shows that specific genes in cluster 2 are closely associated with various functions. After identifying the cross-core genes, machine learning models indicate that generalized linear models have better accuracy. Ultimately, a generalized linear model for five highly correlated genes was constructed, and validation with an external dataset showed an AUC of 0.982. The accuracy of the model was further verified through calibration curves, decision curves, and modal graphs. Further analysis of clinical relevance revealed that these correlated genes were closely related to time of injury. Conclusion: This study has revealed the intricate relationship between cuproptosis and major burns. Research has identified 15 cuproptosis-related genes that are associated with major burn. Through a machine learning model, five core genes related to cuproptosis and major burn have been selected and validated.

Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis.

BACKGROUND: The prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs. METHODS: Diabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson's trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells. RESULTS: The lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR­126­3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect. CONCLUSION: Decreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.

Mobile Health System for Meeting Health Information Needs in Patients With Head and Neck Cancer Undergoing Radiotherapy: Development and Feasibility Study.

Patients with head and neck cancer undergoing radiotherapy encounter physical and psychosocial challenges, indicating unmet needs. Mobile health technology can potentially support patients. This single-armed feasibility study included 30 patients with head and neck cancer undergoing radiotherapy. Patients were asked to use the Health Enjoy System, a mobile health support system that provides a disease-related resource for 1 week. We assessed the usability of the system and its limited efficacy in meeting patients' health information needs. The result showed that the system was well received by patients and effectively met their health information needs. They also reported free comments on the system's content, backend maintenance, and user engagement. This study supplies a foundation for further research to explore the potential benefits of the Health Enjoy System in supporting patients with head and neck cancer.

Real-world safety of icosapent ethyl: analysis based on spontaneous reports in FAERS database.

BACKGROUND: The triglyceride-lowering drug, icosapent ethyl (IPE), was granted a new indication for the reduction of atherosclerotic cardiovascular disease risk in 2019. This study aimed to investigate the safety profile of IPE by mining the FDA Adverse Event Reporting System (FAERS) database. METHODS: The reporting odds ratio was used to analyze IPE's adverse events (AEs) based on the FAERS data from July 2012 to December 2022. We described the characteristics of AE reports and evaluated the clinical prioritization of AEs. Then we defined and analyzed nine interested adverse drug reactions (ADRs) in both overall and subgroups, and investigated the times to onset. RESULTS: The findings of our study strengthen the evidence for an increased risk of atrial fibrillation using IPE. IPE alone may not increase the risk of bleeding unless combined with antithrombotic drugs. Similar to statins, IPE alone can increase the risk of musculoskeletal pain, drug-related hepatic disorders, and hyperglycemia, but the risk could not double when IPE was combined with statins. Most ADRs occur in the early stage of treatment. CONCLUSIONS: This study provides a comprehensive real-world safety profile of IPE, which indicates that IPE is well-tolerated.

Ten-year phantom limb pain with only four sessions of Fu's subcutaneous needling: A case report and systematic review.

Phantom limb pain (PLP) is a distressing consequence commonly encountered by individuals who have undergone amputations. The efficacy of treatment options for PLP is limited. In this study, we present a case of a 64-year-old male who suffered from PLP for a duration of 10 years following an above-the-knee amputation. Despite unsuccessful attempts with painkillers and neurotrophic drugs over the course of a decade, the patient sought relief through Fu's Subcutaneous Needling (FSN), an innovative acupuncture therapy that specifically targets the subcutaneous tissue for pain management. Remarkably, the patient experienced a significant reduction in PLP and subsequently decreased his reliance on medication, as well as experiencing improved sleep after undergoing one session of FSN per day for four consecutive days. A follow-up conducted three years later demonstrated positive treatment outcomes. FSN demonstrated a significant influence on PLP, resulting in reduced analgesic requirements and enhanced quality of life. Therefore, FSN may be recommended as an additional treatment option for PLP. In order to gain a comprehensive understanding of the effects of acupuncture on PLP, a systematic review of relevant literature was conducted in PubMed, Embase, Cochrane Library and Web of Science in recent 20 years (from January 1, 2003 to October 16, 2023), using different combinations of the following terms: (phantom acrodynia), (residual limb pain), (phantom limb pain), (acupuncture), (electroacupuncture), (auriculoacupuncture), and (needling). 9 articles with 18 cases including one randomized controlled trial (n = 8) were obtained. This review provided additional evidence supporting the efficacy and safety of needling therapies for PLP. This systematic review offers additional evidence supporting the effectiveness and safety of needling therapies for PLP. However, there were no precedent reports using FSN treatment for PLP. Hence, this case may provide some implications for clinicians in practice.

Fu's subcutaneous needling as an adjunctive therapy for diaphragmatic dysfunction in a critically ill patient with severe neurologic disability: A case report.

RATIONALE: Diaphragmatic dysfunction is prevalent among intensive care unit patients. The use of Fu's subcutaneous needling (FSN) for respiratory problems is a new issue and few study has been conducted so far. PATIENT CONCERNS: Despite conventional treatments, the patient continued using noninvasive ventilation after discharge from the intensive care unit due to diaphragmatic dysfunction. DIAGNOSIS: Diaphragmatic dysfunction. INTERVENTIONS: After the myofascial trigger points were confirmed in the neck, chest, and abdomen area, FSN therapy was performed using disposable FSN needles. FSN needles were penetrated into the subcutaneous layer. OUTCOMES: The patient dyspnea and tachypnea improved, and noninvasive ventilation time dropped significantly. The patient was successfully weaned from the ventilator after 3 sessions of FSN therapy, and there was an increase in diaphragmatic excursion and tidal fraction of the diaphragm via the ultrasound imaging. We found no evidence of relapse 12 months after treatment. LESSONS: FSN therapy has potential as an alternative strategy for patients with diaphragmatic dysfunction and severe neurologic disabilities who do not respond well to conventional therapies, but further research is still required to establish the effects of FSN on diaphragmatic function.

Bisphosphonates-related tendinopathies and ligament disorders: Cases analysis from the U.S. Food and Drug Administration adverse event reporting system.

Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such adverse reactions result from the use of bisphosphonates (BPs). In this study, we assessed the correlation between TPLDs and the use of BPs via U.S. FDA Adverse Event Reporting System (FAERS) database. Bayesian and nonproportional analyses were applied to data retrieved from the FAERS database from the first quarter of 2004 to the third quarter of 2022. A total of 3202 reported cases of TPLDs were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, zoledronate), with statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC). Alendronate showed the highest association with tendinopathies and ligament disorders (ROR = 16.30, PRR = 15.47, IC = 3.88), while zoledronate had the lowest association (ROR = 2.13, PRR = 2.12, IC = 1.08), which was consistent with the results of top 10 preferred terms (PTs) under the narrow standardized MedDRA queries (SMQs) sorted by frequency of reports. Excluding zoledronate, over half of patients who reported BP-related TPLDs were hospitalized, either briefly or extendedly. This was especially true for alendronate, which showed the highest rate of hospitalization (83.25 %), however, the mortality rate reported by those taking alendronate were significantly lower than those of zoledronate and pamidronate. In addition, the clinical characteristics of BP-related TPLDs was analyzed. It is more common to reported in middle-aged and elderly females, the highest proportion was in 50-69 years old. Except for osteoporosis, osteopenia, and osteoporosis prophylaxis, cancer bone metastasis was also the indication of some BPs. The most often reported concomitant/prior medicines were calcium supplements, another BPs, antitumor agents, and nonsteroidal anti-inflammatory drugs. In conclusion, we provide a comprehensive overview of the correlation and clinical characteristics, and prognosis of BP-related TPLDs deserving continued surveillance and appropriate management.

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

Fu'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's body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat'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.

Upregulation of circ_0080968 in diabetic foot ulcer inhibits wound healing via repressing the migration and promoting proliferation of keratinocytes.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus whose pathogenesis remains unclear. Circular RNA (circRNA) refers to a group of covalently closed non-coding RNAs that are reported to be dysregulated in patients with DFU. However, the mechanism whereby dysregulation in circRNAs contributes to DFU remains unclear. In this study, we investigated the role of dysregulated circRNAs in DFU. MATERIALS AND METHODS: A gene expression dataset was downloaded from the Gene Expression Omnibus portal and analyzed by the limma package of R. The levels of 24 upregulated circRNAs were detected in two independent cohorts by RT-qPCR. Interactions between miRNAs and circRNAs were predicted through bioinformatics and confirmed using a dual luciferase assay. The circularity and subcellular localization of circRNA-080968 was examined by northern blotting after digestion with RNase-R and in situ hybridization. Cell migration and proliferation were examined using Transwell and MTT assays. The apoptotic cells were detected by flow cytometry. RESULTS: The level of circRNA-080968 was upregulated in DFU tissues compared to that of non-DFU samples and normal human wounds. CircRNA-080968 was mainly localized in the cytoplasm and its overexpression inhibited the migration and promoted the proliferation of keratinocytes. MiR-326 and miR-766-3p were identified to interact with and be negatively correlated with circRNA-080968 levels. Increased glucose upregulated circRNA-080968, and its overexpression accelerated the degradation of both miR-326 and miR-766-3p. Reduced levels of miR-326 and miR-766-3p upregulated the expression of several genes controlling cell adhesion and proliferation which are related to the pathogenesis of DFU. CONCLUSIONS: The upregulation of circRNA-080968 in DFU induced the degradation of miR-326 and miR-766-3p, which further repressed the migration and increased the proliferation of keratinocytes.

Treatment of postsurgical gastroparesis syndrome with Fu's subcutaneous needling: A case report.

Postsurgical gastroparesis syndrome is a syndrome of significantly delayed gastric emptying in the absence of mechanical obstruction after surgery. We presented a case of 69-year-old male patient who suffered from progressive nausea, vomiting and stomach fullness, with a bloating abdomen ten days after laparoscopic radical gastrectomy for gastric cancer. Conventional treatments such as gastrointestinal decompression, gastric acid suppression therapy and intravenous nutritional support were administrated, but there were no obvious improvements in nausea, vomiting, abdominal distension of this patient. Fu's subcutaneous needling was performed once a day for three days, for a total of three treatments. After three days of Fu's subcutaneous needling intervention, he was free of symptoms of nausea, vomiting and stomach fullness. His gastric drainage volume reduced from 1000 ml per day to 10 ml per day. Upper gastrointestinal angiography showed normal peristalsis of remnant stomach. In this case report, Fu's subcutaneous needling showed a potential role of gastrointestinal motility enhancement and gastric drainage volume decrement, which provided a safe and convenient method in palliative care of postsurgical gastroparesis syndrome.

Fu's Subcutaneous Needling for Knee Osteoarthritis Pain.

Fu's subcutaneous needling (FSN) is a new acupuncture and dry needling technique based on traditional Chinese medicine. It rapidly produces long-lasting effects in soft tissue injuries, particularly in painful musculoskeletal conditions, by providing stimulation primarily in the subcutaneous area. Osteoarthritis (OA) is the most common joint disease in adults worldwide and is often accompanied by a painful syndrome of structural changes in the peripheral joints of the knee. However, the etiology of OA pain is not fully understood, though myofascial trigger points (MTrPs) are commonly found in the lower limb muscles (so-called "tightened muscles") of patients with knee OA. FSN has been used in many fields for the treatment of acute pain problems and can relieve muscle contraction from MTrPs, thereby improving the local circulation. This study recruited patients with pain from knee OA into an FSN group or a transcutaneous electrical nerve stimulation (TENS) group with three treatment sessions and a follow-up over the course of 2 weeks. The results showed that FSN was effective in treating soft tissue pain around the knee with OA. This study aimed to establish and visualize three key technical indicators during FSN therapy, including the FSN needle insertion point and layer; the frequency and duration of the swaying movement; and the manipulation of the reperfusion approach. These findings have great potential for future applications in myofascial pain treatment, especially for pain management. Following this protocol could enhance FSN skills.

Treatment of postsurgical trigeminal neuralgia with Fu's subcutaneous needling therapy resulted in prompt complete relief: Two case reports.

RATIONALE: Trigeminal neuralgia is a recurrent unilateral transient electroshock-like pain. Fu's subcutaneous needling (FSN), used to treat the musculoskeletal problems, has not been reported in this field. PATIENT CONCERNS: The pain extent of case 1 had no reduction after the previous microvascular decompression, the pain of case 2 relapsed 4 years after the microvascular decompression. DIAGNOSES: Postsurgical trigeminal neuralgia. INTERVENTIONS: FSN therapy was applied on the muscles around the neck and face area, which the myofascial trigger points were palpated in these muscles. The FSN needle was inserted into the subcutaneous layer and the needle tip was pointed toward the myofascial trigger point. OUTCOMES: The following outcome measurements were observed before and after treatment, including numerical rating scale, Barrow Neurology Institute Pain Scale scores, Constant Face Pain Questionnaire scores, Brief Pain Inventory-Facial scores, Patient Global Impression of Change scores, and medication dosage. The follow-up surveys were made after 2 and 4 months respectively. The pain of Case 1 was significantly reduced after 7 times FSN treatments and the pain of Case 2 was even disappeared after 6 times FSN treatments. LESSONS: This case report suggested that FSN can relieve postsurgical trigeminal neuralgia safely and effectively. Clinical randomized controlled studies are needed to be further conducted.

Subcutaneous stretching enlarges adjacent vertebral artery instantly in patients with cervicogenic dizziness: Two case reports.

RATIONALE: Fu's subcutaneous needling (FSN) is effective for cervicogenic dizziness (CGD), which is often a result of vascular problems. Here, we attribute the positive treatment effect of FSN for CGD to improvements in vascular problems. PATIENT CONCERN: Two patients were experiencing low quality of life due to reproducible dizziness. DIAGNOSIS: Two patients with cervical spine disorder, presented with neck pain and reproducible dizziness. Other causes of dizziness were excluded. INTERVENTIONS: Case 1 received 1 session of FSN treatment, while case 2 received 3 sessions of FSN treatment in a month. OUTCOMES: The dizziness and neck pain experienced by both patients instantly improved significantly after FSN treatment, and the luminal diameter of the vertebral artery (VA) measured by carotid and VA ultrasound enlarged simultaneously up to 1.29-fold and 1.09-fold for both cases. According to the Hagen-Poiseuille equation, the blood flow volume increased 2.77-fold and 1.43-fold, respectively. Case 2 recovered from CGD with 1.19-fold VA luminal diameter increment and about 2.01-fold increase of blood flow volume in a month. LESSONS: Subcutaneous stretching provides a safe, convenient and immediate solution to CGD, and supports the diagnosis and treatment of CGD under carotid and VA ultrasound. This study suggests that stretching subcutaneously can influence adjacent VA, which may also help improve some cerebrovascular diseases.

Gene detection in a family with monilethrix and treatment with 5% topical minoxidil.

OBJECTIVE: To determine the causative gene mutation in a family with monilethrix and observe the therapeutic effect of 5% topical minoxidil. METHOD: Clinical data from a family with monilethrix were collected. Peripheral blood samples were taken from the proband, the parents, and 100 unrelated healthy controls. Genomic DNA was extracted. The genetic variation sites were screened with exome sequencing and verified by Sanger sequencing. The proband was treated with 5% topical minoxidil (1 mL twice daily). Hair quality was examined by dermoscopy before and after treatment. RESULTS: The proband and her father have the heterozygous missense variant c.1204G > A (p.E402K) in exon 7 of the KRT86 gene. However, the mutation was not found in the mother and healthy controls. The proband was treated with 5% topical minoxidil. Hair density and hair shaft quality improved significantly after 6 months of treatment. No adverse events occurred during treatment. CONCLUSION: This study shows that p.E402K is a mutation "hot spot" in patients with autosomal dominant monilethrix in China. Treatment with 5% topical minoxidil, is safe and effective.

Efficacy of Fu's Subcutaneous Needling in Treating Soft Tissue Pain of Knee Osteoarthritis: A Randomized Clinical Trial.

Purpose: Fu's subcutaneous needling (FSN) is a new acupuncture technique that produces a long-lasting effect in soft-tissue injuries. In patients with degenerative knee osteoarthritis (OA), myofascial trigger points (MTrPs) are common in the lower-limb muscles. In this randomized clinical trial, we evaluated the immediate, 1-week and 2-week effectiveness of FSN therapy in the treatment of degenerative knee OA. Patients and methods: We randomly divided 32 patients with knee OA into the FSN group (mean age: 65.73 ± 6.79 years) or the transcutaneous electrical nerve stimulation (TENS) group (mean age: 62.81 ± 5.72 years). The pressure pain threshold (PPT) and tissue hardness (TH) of the muscle and tendon attachment sites, knee range of motion, and physical ability (average walking speed) were measured. The subjective pain intensity index, Western Ontario and McMaster Universities OA Index (WOMAC), and Lequesne index were used to determine the efficacy of FSN on MTrP-induced soft-tissue pain compared with that of TENS. Results: A significantly greater improvement in pain qualities in the VAS (p < 0.05) was found in the FSN group. Moreover, in muscle and tendon qualities (including PPT and TH), a significant difference in the PPT of the quadriceps muscle (p < 0.05) was also observed among the immediate treatments in the FSN group. As for the functional index questionnaire assessment, the FSN group exhibited significant improvements among the immediate, 1-week and 2-week efficacies in terms of WOMAC (p < 0.05) and Lequesne index scores (p < 0.05). Conclusion: FSN was effective in treating soft-tissue pain in degenerative knee OA in terms of alleviating pain, strengthening walking ability, and improving overall functional performance. Pain relief was the primary benefit of FSN and a significant correlation between pain relief and knee joint mobility improvement was found. Trial registration: ClinicalTrials.gov Protocol Registration and Results System (registration number: NCT04356651).

Adjacent Fu's subcutaneous needling as an adjunctive healing strategy for diabetic foot ulcers: Two case reports.

RATIONALE: Diabetic foot ulcers (DFUs) present with different grades of ischemia and infection and are associated with high mortality and disability rates with little effective treatment. We used Fu Subcutaneous Needling (FSN) to treat 2 cases with DFUs and achieved satisfactory results. PATIENT CONCERNS: Two cases of DFUs showed poor recovery after conventional wound care treatment, and case 2 was confronted with the risk of amputation. DIAGNOSIS: Two patients with history of diabetes were diagnosed with DFUs, presenting with lower leg and foot ulcers. INTERVENTIONS: Case 1 received 6 sessions of FSN treatment in 8 days, and case 2 received 10 sessions of FSN treatment in 14 days. OUTCOMES: Case 1 completely healed from a 1 × 0.5-cm blister and a 0.5 × 0.5-cm ulcer of the right lower leg 14 days after the first FSN treatment. The ulcer area of the left foot in case 2 decreased from 6 × 7 cm to 4 × 3.5 × 0.2 cm. Three months of follow-up revealed full wound closure. LESSONS: FSN is effective for healing with DFUs, and it may be used as an adjunctive healing strategy for DFUs patients when conventional treatments such as infection, glycemic control, and local ulcer care are not available.

Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages.

Metformin, a biguanide, exerts different functions through various signaling pathways. In order to investigate the function and mechanism of metformin in burn wounds, we established burn rat models, subcutaneously injected metformin to treat the wounds, and observed the morphologies and the expression of collagen I, collagen III, fibronectin, and pro-inflammatory markers. In vitro experiments were performed to investigate the effects of metformin on the proliferation, migration, and collagen I synthesis of the mouse embryonic fibroblast (NIH 3T3) cell line and on the proliferation, apoptosis, and immune response of the mouse mononuclear macrophage (RAW 264.7) cell line. Finally, we studied the regulatory effects of metformin on a co-culture of RAW 264.7/NIH 3T3 cells. We found that 100 mM of metformin reduced dermal thickness, collagen I deposition, and mRNA expression of IL1ß and CCL2 in rat burn wounds. In vitro experiments revealed that metformin inhibited the proliferation of NIH 3T3 and RAW 264.7 cells. Metformin attenuated NIH 3T3 cell migration via the AMPK/mTOR pathway and attenuated collagen I synthesis through the TGFß1/Smad3 pathway. Metformin inhibited the apoptosis of RAW 264.7 cells induced by 10 µg/mL LPS. Metformin downregulated the mRNA expression of IL1ß and CCL2 in RAW 264.7 cells under 1 µg/mL LPS induction by inhibiting NF-κB p65 phosphorylation. In a RAW 264.7/NIH 3T3 co-culture, metformin attenuated collagen I synthesis in NIH 3T3 cells by inhibiting RAW 264.7 paracrine secretion of TGF-ß1. This provides new evidence related to the development of metformin for potentially improving burn wound healing.

Rapid Improvement in Neck Disability, Mobility, and Sleep Quality with Chronic Neck Pain Treated by Fu's Subcutaneous Needling: A Randomized Control Study.

Background: Chronic neck pain is a common musculoskeletal disorder caused by overuse of neck and upper back muscles or poor posture, and it is commonly combined with a limited range of motion in the neck and shoulders. Most cases will recover within a few days; however, the symptoms often recur easily. Fu's subcutaneous needling (FSN) is a new therapeutic approach used to treat patients with chronic neck pain. However, there is no solid evidence to support the effectiveness of FSN on chronic neck pain and disability. Methods: Participants (n = 60) with chronic neck pain for more than 2 months with pain intensity scored by visual analog scale (VAS) more than five were enrolled in this trial. Participants were equally randomized into the FSN or transcutaneous electrical nerve stimulation (TENS) group who received interventions once a day on day 1, day 2, and day 4. They were assessed by outcome measurements during pre- and post-treatment and followed up for 15 days. Results: The VAS was immediately reduced in the FSN and TENS groups and sustained for 15 days of follow-up (all P < 0.001). The immediate effects were also observed as the pressure pain threshold increased in the FSN group on day 2 (P=0.006) and day 4 (P=0.023) after treatment, and tissue hardness decreased by FSN on day 1 and day 2 after treatment (both P < 0.001). FSN and TENS treatment improved neck disability and mobility; moreover, FSN promoted participants to receive better sleep quality, as determined by PSQI assessment (P=0.030). TENS had no benefit on sleep quality. Conclusion: FSN was able to relieve pain and relax muscle tightness. Notably, FSN significantly improved neck disability and mobility and enhanced sleep quality. These findings demonstrated that FSN could be an effective alternative treatment option for patients with chronic neck pain. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT03605576, registered on July 30, 2018.

Efficacy of Fu's Subcutaneous Needling on Myofascial Trigger Points for Lateral Epicondylalgia: A Randomized Control Trial.

Lateral epicondylalgia (LE), a common overuse syndrome of the extensor muscle and tendons on the lateral epicondyle, causes persistent severe musculoskeletal pain on the outer part of the elbow. Fu's subcutaneous needling (FSN), a newly invented subtype of acupuncture and dry needling, is a new trend and potential treatment of LE by targeting the myofascial trigger points (MTrPs). However, no scientific evidence is available to support this method. This study aims to evaluate the distal FSN treatment on the LE by measuring pain-related scales, such as visual analog scale (VAS), pressure pain threshold (PPT), muscle tissue hardness (TH), pain-free grip (PFG), and the functional outcome by a patient-rated tennis elbow evaluation (PRTEE) questionnaire study. A total of 60 LE patients were randomly divided into FSN (n = 30) and transcutaneous electrical nerve stimulation (TENS, n = 30) as the control group. Every subject was treated with three regimens and followed up for 15 days. Results showed that FSN has an immediate effect on VAS, PPT, TH, and PFG. Moreover, sustained effects on pain relief were followed up to 15 days. Pain remission was consistent with long-term PRTEE results. Overall, FSN is a safe and efficient therapy option for LE, significantly improving pain relief and activity difficulty with immediate, short-term, and long-term effectiveness. This trial is registered with ClinicalTrials.gov NCT03605563.