Effect of l-Carnitine Supplementation on Osteoarthritis: A Systematic Review.

SCOPE: Comprehensive assessment of l-carnitine's safety and effectiveness in reducing inflammatory markers in osteoarthritis (OA) patients. METHODS AND RESULTS: Journal articles on l-carnitine for OA are gathered using computer searches of PubMed, Embase, the Cochrane Library, and Web of Science. The kind of literature that is found is restricted to clinical randomized controlled trials (RCTs). The Cochrane Handbook risk of bias assessment tool RevMan 5.4 software is used to conduct a meta-analysis. The systematic assessment comprises eight trials totaling 619 patients; the included studies' quality is mediocre. The study's findings demonstrate that OA patients' Western Ontario and McMaster University (WOMAC) function improves and that treatment efficacy outperforms that of the control group (mean difference [MD] = -7.75, 95% CI [-14.63, -0.86]; Z = 2.21; p = 0.03), WOMAC total (MD = -10.24, 95% CI [-18.97, -1.51]; Z = 2.30; p = 0.02), and visual analogue scale (VAS) pain (MD = -14.01, 95% CI [-16.16, -11.85]; Z = 12.74; p < 0.00001). The studies that are methodically reviewed also discover heterogeneity, which may have resulted from the created pooled data and requires more analysis. CONCLUSION: In patients with OA, l-carnitine effectively decreases clinical signs and symptoms, inflammatory markers, pain, and stiffness indicators, and significantly improves WOMAC and VAS scores.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. MATERIALS AND METHODS: In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. CONCLUSION: The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. TRIAL REGISTRATION: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

Biomechanical effects of typical lower limb movements of Chen-style Tai Chi on knee joint.

The load and stress distribution on cartilage and meniscus of the knee joint in typical lower limb movements of Chen-style Tai Chi (TC) and deep squat (DS) were analyzed using finite element (FE) analysis. The loadings for this analysis consisted of muscle forces and ground reaction force (GRF), which were calculated through the inverse dynamic approach based on kinematics and force plate measurements obtained from motion capture experiments. Thirteen experienced practitioners performed four typical TC movements, namely, single whip (SW), brush knee and twist step (BKTS), stretch down (SD), and part the wild horse's mane (PWHM), which exhibit lower posture and greater lower limb force compared to other TC styles. The results indicated that TC required greater lower limb muscle strength than DS, resulting in greater knee joint forces. The stress on the medial cartilage in SW and BKTS fell within a range conductive to maintaining the balance between anabolism and catabolism of cartilage matrix. This was due to the fact that SW and BKTS reduce the medial to total tibiofemoral contact force ratios through knee abduction, which may effectively alleviate mild medial knee osteoarthritis (KOA). However, the greater medial contact force ratios observed in SD and PWHM resulted in great contact stresses that may aggravate the pain of patients with KOA. To mitigate these effects, practitioners should consider elevating their postures appropriately to reduce knee flexion angles, especially during the single-leg support phase. This adjustment can decrease the required muscle strength, load and stress on the knee joint.

Current Non-surgical Management of Knee Osteoarthritis.

Osteoarthritis (OA) is a common chronic degenerative disease. The prevalence tends to increase with age and is influenced by underlying risk factors such as gender, obesity, joint injuries (work/sports activities), and geographic region. OA has a distinctive picture, namely, damage to the joint cartilage and the formation of new bone at the edges of the bones, also called osteophytes, due to biochemical, metabolic, physiological, and pathological changes in the joint cartilage and subchondral bone. Symptoms that can be caused include joint pain, inhibition of joint movement, crepitus, deformity, asymmetrical swelling of the joints, signs of inflammation, and changes in gait. Currently, there are various methods of managing OA in terms of reducing pain, including regeneration and non-regeneration therapy. Non-regeneration treatments include physiotherapy (exercise, biomechanical intervention, electrotherapy, diathermy), pharmacology, intra-articular injections (corticosteroids, hyaluronic acid, geniculate nerve blocks), extra-articular injections, and radiofrequency. In comparison, regeneration management includes laser and intra-articular injection (prolotherapy and PRP).

L-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway.

BACKGROUND: Knee osteoarthritis (KOA) is a disability-associated condition that is rapidly growing with the increase in obesity rates worldwide. There is a pressing need for precise management and timely intervention in the development of KOA. L-carnitine has been frequently recommended as a supplement to increase physical activity in obese individuals due to its role in fatty acid metabolism, immune disorders, and in maintaining the mitochondrial acetyl-CoA/CoA ratio. In this study, we aimed to investigate the anti-inflammatory effects of L-carnitine on KOA and delineate a potential molecular mechanism. METHODS: Lipopolysaccharide-stimulated primary rat fibroblast-like synoviocytes (FLS) were treated with an AMP-activated protein kinase (AMPK) inhibitor or siRNA and carnitine palmitoyltransferase 1 (CPT1) siRNA to examine the synovial protective effects of L-carnitine. An anterior cruciate ligament transection model of rats was treated with an AMPK agonist (metformin) and CPT1 inhibitor (etomoxir) to define the therapeutic effects of L-carnitine. RESULTS: L-carnitine displayed a protective effect against synovitis of KOA in vitro and in vivo experiments. Specifically, L-carnitine treatment can reduce synovitis by inhibiting AMPK-ACC-CPT1 pathway activation and showed an increase in fatty acid ß-oxidation, a lower lipid accumulation, and a noticeable improvement in mitochondrial function. CONCLUSIONS: Our data suggested that L-carnitine can mitigate synovitis in FLS and synovial tissue, and the underlying mechanism may be related to improving mitochondrial function and reducing lipid accumulation via the AMPK-ACC-CPT1 signaling pathway. Therefore, L-carnitine may be a potential treatment strategy for KOA.

[Effect of needle-knife on chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis based on CircSERPINE2-miR-1271-5P-ERG axis].

OBJECTIVE: To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA. METHODS: Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group. RESULTS: After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01). CONCLUSION: Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.

Combined Administration of Curcumin and Chondroitin Sulfate Alleviates Cartilage Injury and Inflammation via NF-κB Pathway in Knee Osteoarthritis Rats.

Objective: Osteoarthritis (OA) is a degenerative chronic disease that most often occurs in the knee joint. Studies have shown that some food supplements, such as curcumin and chondroitin sulfate, are effective in treating knee osteoarthritis (KOA) by exhibiting different protective effects. In this study, we further investigated the combined therapeutic effects of curcumin and chondroitin sulfate on cartilage injury in rats with arthritis. Methods: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. All rats were randomly divided into five groups: Ctrl (control), model (saline), Cur (20 mg/kg curcumin in saline), CS (100 mg/kg chondroitin sulfate in saline), and CA (20 mg/kg curcumin and 100 mg/kg chondroitin sulfate in saline); drugs were given 2 weeks after MIA injection. The histomorphological changes of cartilage were observed by safranin fast green staining, H&E staining, and micro-CT scanning. Also, the levels of PGE2, TNF-α and IL-1ß in the arthral fluid and serum were determined by the ELISA kits. The activities of SOD, CAT, COMP, MMP-3, and type II collagen were detected by biochemical kits. The expressions of TLR4, p-NF-κB, NF-κB, and COX-2 in cartilage were detected by Western blot. Results: Data show that serum levels of IL-1ß (p < 0.05), SOD (p < 0.0001), and MMP-3 (p < 0.001) were downregulated significantly in the CA group when compared to those in the model group. Meanwhile, obvious repair of cartilage with higher contains collagen II (p < 0.0001) could be observed in the CA group than the ones in Cur or CS group. In addition, significant downregulation of the expression of p-p65/p65 (p < 0.05) was found in the CA group. Conclusion: Our findings showed that combined administration of curcumin and chondroitin sulfate could exert better repair for KOA in rat models. This may hold great promise for discovering potential drugs to treat KOA and may improve treatment options for it.

Spinal 5-HT2A receptor is involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord. 5-HT2A is a G protein-coupled receptor and it is involved in 5-HT descending pain modulation system. We found that EA treatment at frequency of 2 Hz +1 mA significantly increased the expression of 5-HT2A receptor in the dorsal spinal cord and intrathecal injection of 5-HT2A receptor antagonist or agonist reversed or mimicked the analgesic effect of EA in each case respectively. Intrathecal injection of a selective GABAA receptor antagonist Bicuculline also reversed the EA effect on pain hypersensitivity. Additionally, EA treatment reversed the reduced expression of GABAA receptor and KCC2 in the dorsal spinal cord of KOA mice. Furthermore, we demonstrated that intrathecal 5-HT2A receptor antagonist/agonist reversed or mimicked the effect of EA up-regulate of KCC2 expression, respectively. Similarly, intrathecal injection of PLC and PKC inhibitors prevented both anti-allodynic effect and up-regulation of KCC2 expression by EA treatment. Our data suggest that EA treatment up-regulated KCC2 expression through activating 5-HT2A-Gq-PLC-PKC pathway and enhanced the inhibitory function of GABAA receptor, thereby inhibiting chronic pain in a mouse model of KOA.

Inhibiting the Musculoskeletal Pathological Processes in Post-knee Replacement Surgery With Osteopathic Manipulative Treatment: A Systematic Review.

Total knee arthroplasty (TKA) is a very common surgical treatment approach for severe osteoarthritis. Complications of TKA include loss of range of motion and prolonged analgesic requirement for pain control. Osteopathic manipulative techniques (OMT) have been utilized to address localized muscular stiffness to improve range of motion; however, limited studies directly correlate OMT and TKA recovery. This review highlights the therapeutic benefits OMT can have in the postoperative management of arthroplasty with respect to range of motion, edema, pain perception, and ability to perform activities of daily living. This review revealed the use of OMT would positively influence range of motion by manipulation of localized musculature and can result in decreased demand for analgesics. This can, in turn, shorten hospital stay and return the ability of patients to perform activities of daily living earlier than without OMT. Increased research is needed to strengthen these findings on the benefits of OMT in the postoperative management of arthroplasty.

Cangxitongbi capsules protect the articular cartilage in the rat knee through the long non-coding RNA HOTAIR/p38MAPK pathway.

BACKGROUND: Knee osteoarthritis (KOA) is a leading cause of chronic pain and disability, and as such, it poses a significant economic burden. Traditional Chinese medicine (TCM), as well as complementary and alternative medicine, can offer safe and effective treatments for KOA. Cangxitongbi (CXTB) capsule is a Chinese patented medicine for KOA treatment and has a remarkable curative effect. This article evaluated the effects and mechanisms of CXTB in protecting joint cartilage in vivo. METHODS: The KOA model was constructed in rats using the modified Hulth method. CXTB (35 mg/kg) was administered intragastrically for 4 weeks. Hematoxylin and eosin (HE) staining of the knee articular were performed to evaluate the efficiency of CXTB. Western blot analysis, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA) were used to investigate the protective mechanisms of CXTB in joint cartilage. RESULTS: CXTB effectively improved the morphological structure of the cartilage and bone in the knee joint by enhancing autophagy and regulating the expression of related protease and inflammatory factors. Furthermore, CXTB downregulated the expression of the long non-coding RNA (lncRNA) Hox transcript antisense intergenic RNA (HOTAIR) and inhibited the activation of the p38MAPK pathway. Conversely, overexpression of lncRNA HOTAIR suppressed the protective effects of CXTB on the knee joint. CONCLUSIONS: CXTB capsules can protect the knee articular cartilage in rats through the lncRNA HOTAIR/p38MAPK pathway.

A systematic review and meta-analysis of the comparative curative effects of warm acupuncture and other traditional Chinese medicines in the treatment of knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is more common in middle-aged and elderly people, and seriously affects the quality of life of those affected. Traditional Chinese medicine (TCM) treatment of KOA has been widely recognized. In recent years, warm needling acupuncture (WNA) has been used to treat KOA and has achieved good results. However, there is a lack of comparison of the efficacy of WNA and other TCM treatments for KOA. METHODS: We conducted a search for reports of WNA and/or TCM treatment of KOA in English- and Chinese-language databases. The data was retrieved from inception of the database until October 2021. The Cochrane risk of bias tool was used to evaluate the quality of the included studies, and the network meta-analysis was performed using the software RevMan 5.20. RESULTS: A total of 8 articles met the inclusion criteria, including 399 patients treated with WNA (WNA group), and 396 patients treated with other TCM (TCM group). The results of meta-analysis showed that compared with patients in the TCM group, the effective rate [relative risk (RR)] was 1.18, 95% confidence interval (CI): 1.06 to 1.33, the last follow-up osteoarthritis index [mean difference (MD)] was -6.93, 95% CI: -12.14 to -1.72, and the last follow-up knee pain visual analogue scale (VAS) MD was -1.06, 95% CI: -1.61 to -0.51, which were all statistically significant. However, the difference in daily activities (MD: -4.31, 95% CI: -10.90 to 2.28) was not statistically significant. DISCUSSION: Compared with other TCM treatments for KOA, WNA has better overall patient efficacy. However, further randomized controlled studies are needed to compare WNA and other TCM treatments individually to confirm the efficacy of WNA.

The comparison of curcuminoid formulations or its combination with conventional therapies versus conventional therapies alone for knee osteoarthritis.

BACKGROUND: Presently, curcuminoid formulations or its combination with conventional therapies has been used for the treatment of knee osteoarthritis (KOA). Nevertheless, evidence is limited due to small-sized clinical trials. This study aims to evaluate the efficacy of curcuminoid formulations or its combination with conventional therapies for KOA. METHODS: Randomized controlled trials comparing curcuminoid formulations or its combination with conventional therapies versus conventional therapies, such as non-steroidal antiinflammatory drugs (NSAIDs) and chondroitin sulfate/glucosamine, were searched from databases. RESULTS: In total, 14 studies involving 1533 patients were included. Curcuminoid formulations were comparative to NSAIDs in reducing Visual Analogue Scale (VAS), total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and WOMAC score for pain/stiffness/physical function. No significant difference was seen between the two groups in terms of patients' satisfaction index, patients' global assessment, reduction of several inflammatory factor, rate of drug compliance, and rescue medication. Notably, curcuminoid formulations combined with NSAIDs significantly reduced VAS and WOMAC/Knee injury and OA Outcome Score (KOOS) pain score more than NSAIDs did. In addition, the curcuminoid formulations were superior to chondroitin sulfate/glucosamine in reducing VAS, total WOMAC score, and WOMAC score for stiffness/difficulty in physical function, while no significant difference was seen in reducing WOMAC pain score and Karnofsky Performance Scale score. CONCLUSIONS: Curcuminoid formulations may be considered a promising alternative for treating KOA. Key points • Curcuminoid formulations are comparative to NSAIDs for KOA. • Curcuminoid formulations are superior to chondroitin sulfate/glucosamine for KOA. • Curcuminoid formulations could provide additional benefits in alleviating pain and some adverse events caused by NSAIDs.

Self-administered acupressure and exercise for patients with osteoarthritis: A randomized controlled trial.

OBJECTIVE: Knee osteoarthritis is a prevalent degenerative joint disease and seriously affects the athletic abilities of middle-aged and elderly patients. Acupressure is a traditional non-pharmacological intervention that promotes blood circulation and muscle activity. Self-administrated acupressure and exercise can be potential management for knee osteoarthritis. DESIGN: It is a randomized and controlled trial for knee osteoarthritis self-treatment. SETTINGS: Cangzhou Hospital. INTERVENTIONS: 221 patients with knee osteoarthritis were recruited and randomly divided into 4 groups: control group (n = 55), exercise group (n = 56), acupressure group (n = 55) and exercise & acupressure group (n = 55). In the first eight weeks, corresponding training courses were provided to different groups of patients. The patients were asked to carry out their own corresponding interventions for 16 weeks. The patient's condition was evaluated in the sixteenth week. MAIN MEASURES: The Western Ontario and McMaster Universities global scores of knee osteoarthritis patients were assessed at the 8th and 16th week of our trial. RESULTS: Self-administered acupressure and exercise significantly decreased visual analogue scale (3.75 ± 1.89 versus 2.93 ± 1.73, p < 0.05), pain (7.6 ± 2.8 versus 4.8 ± 2.7, p < 0.05), stiffness (3.75 ± 1.89 versus 2.93 ± 1.73, p < 0.05) at the 16th week (p < 0.05) in patients with knee osteoarthritis compared to other intervention. The combination of acupressure and exercise also improved the range of motion (114.4 ± 11.5 versus 120.4 ± 11.9, p < 0.05) and walk speed (1.48 ± 0.48 versus 1.76 ± 0.50, p < 0.05) of osteoarthritis patients (p < 0.05). CONCLUSION: Self-administrated exercise and acupressure alleviate the arthritic symptoms (swelling, pain, joint dysfunction and joint deformities) and improve the joint functions, supporting its potential use in the clinical management for osteoarthritis.

Functional outcomes of Tai Chi exercise prescription in women with knee osteoarthritis.

Knee Osteoarthritis (KOA) is the most common type of knee joint injury and also a risk factor for multiple health consequences and is prevalent among older women. The updated clinical guidelines for KOA treatment by the American Rheumatism Association recommend Tai Chi exercise. However, a literature review outlined limitations in Tai Chi intervention implementations. This study aimed to address some of the gaps. This study selected thirty female patients to participate in Tai Chi exercises and undergo relevant tests. The subjects were randomly assigned to Tai Chi or education groups. Independent sample t-tests were conducted to compare the difference in health indicators between the two groups after the intervention. The difference-in-differences (DID) regression was performed to assess the difference in the health outcomes between the two groups at baseline and follow-up and the difference in the differences. After the completion of the intervention, the Tai Chi group reported significantly improved KOA symptoms, physical fitness, and health status indicators than the control group. Specifically, the group differences were significantly larger at the baseline than at the follow-up. Our findings provide compelling evidence of the effects of the innovative Tai Chi exercise prescription specifically designed for KOA patients. The empirical evidence on its effectiveness in alleviating KOA symptoms and improving the overall health of middle-aged and elderly women with KOA suggested that Tai Chi intervention exercise has huge prospects for integration in KOA rehabilitation therapy.

Treatment of knee osteoarthritis with acupuncture combined with Chinese herbal medicine: a systematic review and meta-analysis.

BACKGROUND: Many studies have demonstrated that acupuncture combined with Chinese herbal medicine (CHM) effectively treats knee osteoarthritis (KOA), with few side effects. However, few systematic reviews have offered evidence-based support. Here we conducted a meta-analysis on the combination of acupuncture with CHM in treating KOA. METHODS: Databases including CNKI, Wanfang, VIP, PubMed, EMBASE, and Cochrane library were systematically searched for articles on the treatment of KOA by acupuncture combined with CHM from the establishment of the database to May 2021. Three researchers independently searched, screened, extracted, and included articles that met the inclusion standards. The primary outcome measure was overall response rate (ORR), and the secondary outcome measures included Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Lysholm score. ORR was a binary variable, while other indicators were continuous variables. The quality of literature was assessed with a modified Jadad scale. The RevMan 5.3 software provided by the Cochrane Collaboration was used for statistical analysis. RESULTS: Thirty-three randomized controlled trials involving 3,954 patients were included. Meta-analysis showed that ORR [odds ratio (OR) =5.41; 95% confidence interval (CI): (4.38, 6.68); P<0.00001], VAS score [mean difference (MD) =-1.86; 95% CI: (-2.44, -1.29); P<0.00001], WOMAC score [MD =-13.05; 95% CI: (-21.70, -4.41); P=0.003], and Lysholm score [MD =10.47; 95% CI: (5.21, 15.72); P<0.0001] in the combination group were significantly superior to those in the control group. DISCUSSION: Compared with acupuncture alone or CHM/Western drug alone, acupuncture combined with CHM can effectively alleviate knee pain, improve knee function, and increase the quality of life. Thus, this combination can be used as a conservative treatment for KOA. However, due to the small number of high-quality articles and possible biases in our analysis, our conclusions need to be further verified in more and higher-quality studies.

[Heat-sensitive moxibustion of different suspension moxibustion methods and imitation moxibustion apparatus on moxibustion sensation and clinical efficacy in knee osteoarthritis].

OBJECTIVE: To observe the moxibustion sensation and the clinical therapeutic effect of heat-sensitive moxibustion of two different suspension moxibustion methods and imitation moxibustion apparatus on mild to moderate knee osteoarthritis (KOA), and compare the therapeutic effect of different moxibustion methods. METHODS: A total of 90 patients with mild to moderate KOA were randomized into a hand-held group (30 cases, 1 case dropped off), an imitation moxibustion apparatus group (30 cases) and a moxibustion shelf group (30 cases, 1 case dropped off). Ashi point, Dubi (ST 35), Neixiyan (EX-LE 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Liangqiu (ST 34) and Xuehai (SP 10) were selected as the frequent acupoint areas to explore and determine the heat-sensitive acupoints, after that, hand-held suspension moxibustion, suspension moxibustion with imitation moxibustion apparatus and suspension moxibustion with moxibustion shelf were adopted in the 3 groups respectively. The treatment was given once every 2 days, and totally 10-time treatment was required in the 3 groups. The moxibustion sensation (composition of moxibustion sensation, number of moxibustion sensation types in individuals and moxibustion sensation intensity) after each treatment, the visual analogue scale (VAS) score, the Lysholms knee function score and the depth of effusion and thickness of synovial hyperplasia of affected knee joint before and after treatment were observed, and the clinical therapeutic efficacy was compared in the 3 groups. RESULTS: The compositions of moxibustion sensation and numbers of moxibustion sensation types in individuals in the hand-held group and the moxibustion shelf group were richer, the moxibustion sensation intensity was higher than that in the imitation moxibustion apparatus group (P<0.01, P<0.05). After treatment, the VAS scores were decreased, the Lysholms knee function scores were increased compared before treatment in the 3 groups (P<0.01); the VAS score in the hand-held group was lower than the imitation moxibustion apparatus group (P<0.05), the Lysholms knee function scores in the hand-held group and the moxibustion shelf group were higher than the imitation moxibustion apparatus group (P<0.05). After treatment, the depth of effusion and thickness of synovial hyperplasia of affected knee joint were decreased compared before treatment in the 3 groups (P<0.01), and those in the hand-held group and the moxibustion shelf group were lower than the imitation moxibustion apparatus group (P<0.05). The cured and markedly effective rate in the hand-held group was 79.3% (23/29), which was better than 36.7% (11/30) in the imitation moxibuation apparatus group and 58.6% (17/29) in the moxibustion shelf group (P<0.01, P<0.05). CONCLUSION: Heat-sensitive moxibustion can effectively treat knee osteoarthritis, while the different suspension moxibustion methods have an influence on clinical therapeutic effect, hand-held suspension moxibustion has the best efficacy.

5-HT7 Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord.

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in EA analgesia. The 5-HT7 receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs-cAMP-PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.

Interventional Efects of the Topical of "Sanse Powder" Essential Oils Nanoemulsion on Knee Osteoarthritis in Rats by Targeting the ERS/TXNIP/NLRP3 Signaling Axis.

Purpose: Our recent research is dedicated to finding effective drugs for the treatment of knee osteoarthritis (KOA) from traditional Chinese medicine and trying to make full use of modern science and technology to uncover the mechanisms and targets behind them. Synovial inflammation is one of the key pathological features of KOA, and a growing number of researchers realize that early intervention of synovial inflammation may be able to reverse disease progression. The close association of traditional natural products with modern nanotechnology may be important for improving the anti-synovitis efficacy. The purpose of our research was to explore the anti-synovitis mechanism of NEs-SP-EO that might be associated with the ERS/TXNIP/NLRP3 signalling axis. Methods: Chemical composition of "Sanse Powder" essential oil (SP-EO) and NEs-SP-EO were analyzed by GC-MS. NEs-SP-EO were prepared and characterized by nanoparticle tracking analysis, polydispersity index (PDI), zeta potential (ZP), ultraviolet-visible spectroscopy, and transmission electronic microscopy. The CCK8 assay for cell viability of NEs-SP-EO was performed on fibroblast-like synovial cells (FLSs) and the inflammatory environment was stimulated by LPS to explore the therapeutic mechanisms in vitro. Experiments of NEs-SP-EO in vivo were performed in male SD rats. Results: The GC-MS results showed that 30 compounds were present in SP-EO and 11 components of NEs-SP-EO were identified. The results also showed that the formulation of NEs-SP-EO exhibited suitable particle size, negative charge, and stable system. In vitro and vivo testing, NEs-SP-EO produced anti-synovitis efficacy by reduced the induction of the ERS/TXNIP/NLRP3 signaling axis as well as regulating the overproduction of IL-1ß, IL-18. Conclusion: We have developed a new type of essential oil nanoemulsion from "Sanse Powder" and demonstrated that it can managing synovitis of KOA. Besides, we have initially explored the anti-inflammatory mechanism that may be related to the ERS/TXNIP/NLRP3 signaling axis.

[Ultrasound anatomy and needle-knife insertion approach of common tendon lesions in knee osteoarthritis based on meridian sinew theory].

OBJECTIVE: To explore the ultrasonic anatomical characteristics and needle-knife insertion approach of common tendon lesions in knee osteoarthritis (KOA), so as to provide the references for accurate release of KOA by needle- knife along tendon lesions based on meridian sinew theory. METHODS: Sixty patients with one-knee KOA were selected. High-frequency musculoskeletal ultrasound was used to collect sonograms at the anatomical positions of "Hedingci" "Binwaixia" "Binneixia" and "Yinlingshang". The anatomic levels were marked on the sonograms. The anatomic levels and sonographic features of lesions were compared and analyzed, and the relevant data of needle-knife simulation approach was measured. RESULTS: The "Hedingci" lesions were mainly located at the attachment of quadriceps tendon to patella and suprapatellar bursa. The "Binwaixia" and "Binneixia" lesions were mainly located at the attachment of retinaculum patellae laterale and retinaculum patellae mediale to patella and infrapatellar fat pad. The "Yinlingshang" lesions were mainly located at the attachment of goose foot tendon to medial tibial condyle and bursa of goose foot. With "Hedingci" as an example, when the needle-knife entry point was 1 cm above the patella, the attachment of quadriceps tendon to patella was released, and the average depth of needle-knife was (3.60±0.10) cm, and the needle body was perpendicular to the skin. The average depth of needle-knife for releasing suprapatellar bursa was (2.35±0.17) cm, and the needle body was 45° towards head. CONCLUSION: The musculoskeletal ultrasound could clearly show the local detailed anatomical level, ultrasonic characteristics and anatomical level of common tendon lesions of KOA, and could improve the accuracy of needle-knife along tendon lesions with non-direct vision, which has important reference value for needle-knife medical standardization and standardized operation.

Efficacy and safety of traditional Chinese medicine rehabilitation program in the treatment of knee osteoarthritis: a randomized controlled trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a common joint disease worldwide, and the main cause of pain and disability in the elderly. Due to increased aging and rates of obesity of the global population, the number of patients with KOA is expected to increase. To reduce the burden of KOA, effective and safe interventions should be developed to reduce pain and improve range of motion, functionality, and quality of life. The aim of the proposed randomized controlled study was to evaluate the efficacy and safety of a traditional Chinese medicine (TCM) rehabilitation therapy in the treatment of KOA. METHODS: This multicenter, randomized, double-blind, parallel group, placebo-controlled trial will include a total of 200 patients with KOA. The enrolled patients will be randomly divided into the experimental group (n=100) and control group (n=100). The experimental group will receive basic treatment plus TCM rehabilitation therapy, while the control group will receive basic treatment plus physiotherapy regimen. Primary endpoints will include clinical efficacy outcomes, visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index score, and Knee Outcome Survey Activities of Daily Living Scale score. The data will help determine whether TCM rehabilitation therapy is beneficial for the treatment of KOA. DISCUSSION: The results will provide high-quality guidance for the current clinical treatment of KOA, and provide patients with more options for symptom relief. The findings from this study may provide updated evidence concerning the efficacy and safety of TCM for patients with KOA.