OBJECTIVE: To observe the effect of meridian sinew releasing technique on moxibustion sensation of heat-sensitive moxibustion in patients with knee osteoarthritis (KOA). METHODS: A total of 60 patients with KOA were randomly divided into an observation group and a control group, 30 cases each group. In the observation group, on the basis of the meridian sinew releasing technique, moxibustion sensation exploration method was applied at Dubi (ST 35) area on the affected side. In the control group, moxibustion sensation exploration method was applied at Dubi (ST 35) area on the affected side. The meridian sinew releasing technique was performed for 20 min each time, the moxibustion sensation exploration method was performed for 60 min each time, once a day for 3 days. The excitation rate, latency, duration time and intensity value of moxibustion sensation of heat-sensitive moxibustion were recorded on the 1st, 2nd and 3rd days of exploration in the two groups. RESULTS: The excitation rate on the 3rd day of exploration and total excitation rate in the observation group were higher than the control group (P<0.05). On the 1st, 2nd and 3rd days of exploration, the latency of moxibustion sensation of heat-sensitive moxibustion in the observation group was shorter than the control group (P<0.05), the duration time was longer than the control group (P<0.05), and the intensity value was higher than the control group (P<0.05). CONCLUSION Meridian sinew releasing technique could improve the excitation rate of moxibustion sensation of heat-sensitive moxibustion in patients with KOA, shorten the latency, prolong the duration time, and improve the intensity value.
Humans ; Osteoarthritis, Knee/therapy* ; Hot Temperature ; Meridians ; Moxibustion ; Sensation

OBJECTIVE: To investigate the clinical effect of aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty and the influence on hypercoagulation. METHODS: Seventy-three patients of knee osteoarthritis with lower extremity venous thrombosis after total knee arthroplasty (KOA) were randomly divided into an observation group (37 cases, 2 cases dropped off) and a control group (36 cases, 1 case dropped off). The patients in the control group took orally rivaroxaban tablets, 10 mg a time, once a day. On the basis of the treatment as the control group, the aconite-isolated moxibustion was applied to Yongquan (KI 1) for the patients of the observation group, once daily and 3 moxa cones were used in each treatment. The duration of treatment was 14 days in both groups. Before treatment and 14 days into treatment, the ultrasonic B test was adopted to determine the conditions of lower extremity venous thrombosis in the two groups. Before treatment, 7 and 14 days into treatment, the coagulation indexes (platelet [PLT], prothrombin time [PT], activated partial prothrombin time [APTT], fibrinogen [Fib] and D-dimer[D-D]), the blood flow velocity of the deep femoral vein and the circumference of the affected side were compared between the two groups separately, and the clinical effect was evaluated. RESULTS: Fourteen days into treatment, the venous thrombosis of the lower extremity was relieved in both groups (P<0.05), and that of the observation group was better than the control group (P<0.05). Seven days into treatment, the blood flow velocity of the deep femoral vein was increased compared with that before treatment in the observation group (P<0.05), and the blood flow rate in the observation group was higher than that in the control group (P<0.05). Fourteen days into treatment, PT, APTT and the blood flow velocity of the deep femoral vein were increased in the two groups compared with those before treatment (P<0.05); and PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all reduced in the two groups (P<0.05). Compared with the control group 14 days into treatment, the blood flow velocity of the deep femoral vein was higher (P<0.05), PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all lower in the observation group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 85.7% (30/35) in the control group (P<0.05). CONCLUSION Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban can effectively treat lower extremity venous thrombosis after total knee arthroplasty, relieve hypercoagulation, accelerate the blood flow velocity and alleviate swelling of the lower extremity in the patients with knee osteoarthritis.
Humans ; Rivaroxaban ; Arthroplasty, Replacement, Knee ; Moxibustion ; Aconitum ; Osteoarthritis, Knee/therapy* ; Venous Thrombosis/surgery* ; Lower Extremity

The treatment ideas with acupuncture for knee osteoarthritis (KOA) are explored on the base of Dongyuan needling technology. Regarding the rules of acupoint selection, Zusanli (ST 36) is predominant, the back-shu points are used for the disorders related to the invasion of exogenous factors, and the front-mu points are for the cases caused by internal injury. Besides, the xing-spring points and shu-stream points are preferred. In treatment of KOA, besides the local points, the front-mu points, i.e. Zhongwan (CV 12), Tianshu (ST 25) and Guanyuan (CV 4), are selected specially to tonifying the spleen and stomach. The earth points and acupoints on the earth meridians (i.e. Yinlingquan [SP 9], Xuehai [SP 10], Liangqiu [ST 34], Dubi [ST 35], Zusanli [ST 36] and Yanglingquan [GB 34]) are optional to coordinate yin and yang, essence and qi , and regulate the qi movement of spleen and stomach. The shu-stream points of liver, spleen and kidney meridians (Taichong [LR 3], Taibai [SP 3] and Taixi [KI 3]) are chosen to promote meridian circulation and regulate zangfu functions.
Humans ; Osteoarthritis, Knee ; Acupuncture Therapy ; Meridians ; Acupuncture Points ; Spleen

This paper summarizes professor GUAN Ling's clinical experience in the treatment of knee osteoarthritis (KOA) with structure-based medical acupuncture (SMA). Based on anatomy and biomechanics and through accurate physical examination, SMA adjusts the mechanical imbalance of muscles to relieve KOA dysfunction, and releases nerve compression to attenuate pain symptoms of KOA. In reference to traditional acupoint selection, and in association with painful areas and mechanical deduction, ashi points located at the rectus femoris, vastus intermedius, vastus medialis and vastus lateralis muscles, etc. are specially stimulated with acupuncture; and the rehabilitation training and health education are the adjuvant treatment for the patients.
Humans ; Osteoarthritis, Knee ; Acupuncture Therapy ; Acupuncture Points ; Adjuvants, Immunologic ; Pain ; Quadriceps Muscle

OBJECTIVE: To observe the effect of acupuncture exercise therapy synchronizing isokinetic muscle strength training on the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy. METHODS: A total of 70 patients after meniscectomy under arthroscopy were randomized into an observation group (35 cases, 2 cases were eliminated， 2 cases dropped off) and a control group (35 cases, 2 cases were eliminated, 1 case dropped off). Acupuncture was applied at Chize (LU 5), Neixiyan (EX-LE 4), Dubi (ST 35),Yanglingquan (GB 34), etc. on the affective side in the two groups. After 30 min, the needles of the knee joint area were withdrew, while the needle at elbow was continuously retained, the observation group was given acupuncture exercise therapy synchronizing isokinetic muscle strength training, and the control group was given conventional acupuncture exercise therapy. The treatment was given once a day, 7-day treatment was taken as one course, and totally 4 courses were required in the two groups. Before and after treatment, the knee joint Lysholm score, the knee joint isokinetic muscle strength flexion/extension ratio (H/Q), joint position sense measurement (JPS) and Hamilton anxiety scale (HAMA) score were compared in the two groups. RESULTS: After treatment, the knee joint Lysholm scores and H/Q were increased compared with those before treatment in the two groups (P<0.001), and the knee joint Lysholm score and H/Q in the observation group were higher than those in the control group (P<0.001); the JPS and HAMA scores were decreased compared with those before treatment in the two groups (P<0.001), the JPS and HAMA score in the observation group were lower than those in the control group (P<0.05). CONCLUSION Acupuncture exercise therapy synchronizing isokinetic muscle strength training can effectively improve the motor function, stability and proprioception of knee joint, as well as the anxiety emotion in patients after meniscectomy under arthroscopy.
Humans ; Arthroscopy ; Meniscectomy ; Resistance Training ; Treatment Outcome ; Osteoarthritis, Knee/therapy* ; Acupuncture Therapy ; Exercise Therapy ; Muscles ; Muscle Strength ; Acupuncture Points

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method

Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regeneration＆Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade Ⅲ to grade Ⅱ, one case improved from grade Ⅱ to grade Ⅰ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade Ⅰ,Ⅱ,and Ⅲ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade Ⅰ, 2.66 ms in grade Ⅱ, and 3.72 ms in grade Ⅲ).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.
Humans ; Female ; Male ; Osteoarthritis, Knee/therapy* ; Retrospective Studies ; Orthopedic Procedures ; Platelet-Rich Plasma ; Magnetic Resonance Imaging

OBJECTIVE: To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and in vitro and in vivo biological properties. METHODS: Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the "click chemistry" method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The in vitro degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination. RESULTS: The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (P<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (P<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (P<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (P<0.05). In vivo experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (P<0.05). CONCLUSION HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
Animals ; Rats ; Matrix Metalloproteinase 13 ; Microspheres ; Hydrogels ; Collagen Type II ; Diclofenac ; Inflammation ; Osteoarthritis, Knee/drug therapy* ; Hyaluronic Acid ; Aggrecans

Metabolomics based on ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) was employed to analyze the effect of Cyathulae Radix on serum and urine in rats with knee osteoarthritis, and to decipher the mechanism of Cyathulae Radix in the treatment of knee osteoarthritis. SD rats were randomized into a normal group, a model group, a positive drug group, and a Cyathulae Radix group. The knee osteoarthritis model was established by injecting 2% pa-pain and 0.03 mol·L~(-1) cysteine, and the serum levels of tumor necrosis factor-α(TNF-α) and matrix metalloproteinase-3(MMP-3) in the model group was measured to preliminarily evaluate the therapeutic effect of Cyathulae Radix on knee osteoarthritis. UHPLC-Q-TOF-MS was employed to establish the metabolic profile of endogenous small molecule metabolites in the four groups. Potential biomarkers were screened out by multivariate analysis methods such as partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) in combination with t-test, variable importance for projection(VIP), and fold-change. The related metabolic pathways were enriched with the help of MetaboAnalyst 5.0. The results showed that Cyathulae Radix alleviated the general signs of rats with knee osteoarthritis, and reduced the levels of TNF-α and MMP-3 in the rat serum. Twenty-eight differential metabolites that might be associated with the therapeutic effect of Cyathulae Radix were screened out from serum and urine. They were mainly involved in arginine biosynthesis, nicotinate and nicotinamide metabolism, tricarboxylic acid cycle, alanine, aspartate and glutamate metabolism, riboflavin metabolism, glyoxylate and dicarboxylate metabolism, and pyrimidine metabolism. Through metabonomics analysis, this study predicted the possible mechanism of Cyathulae Radix in the treatment of knee osteoarthritis, which laid a foundation for further research.
Rats ; Animals ; Matrix Metalloproteinase 3 ; Osteoarthritis, Knee/drug therapy* ; Tumor Necrosis Factor-alpha ; Rats, Sprague-Dawley ; Metabolomics/methods* ; Chromatography, High Pressure Liquid/methods* ; Biomarkers

This study aims to assess the efficacy and safety of Hulisan Capsules in the treatment of knee osteoarthritis, which is expected to serve as a reference for clinical practice. To be specific, randomized controlled trial(RCT) on the treatment of knee osteoarthritis with Hulisan Capsules was retrieved from EMbase, PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, SinoMed, and VIP(from inception to November 15, 2021). Two researchers independently screened the articles, extracted the data, and evaluated the risk of bias with ROB. RevMan 5.4 was used for Meta-analysis. Finally, 12 RCTs were screened out, involving 1 703 cases(1 075 in the experimental group and 628 in the control group). Meta-analysis showed that conventional treatment + Hulisan Capsules was superior to conventional treatment alone in terms of symptom relief rate(RR=1.19, 95%CI[1.09, 1.30], P<0.000 1), Lysholm score(MD=11.17, 95%CI[7.35, 15.00], P<0.000 01), visual analogue scale(VAS) score(MD=-0.99, 95%CI[-1.30,-0.68], P<0.000 01), and knee function score(RR=8.94, 95%CI[6.51, 11.37], P<0.000 01). Hulisan Capsules alone was superior to the conventional treatment alone in terms of the symptom relief rate(RR=1.38, 95%CI[1.13, 1.69], P=0.002) and knee function score(MD=2.88, 95%CI[0.81, 4.94], P=0.006), but VAS score was insignificantly different between the patients treated with Hulisan Capsules alone and those with conventional treatment alone(MD=-0.57, 95%CI[-1.42, 0.29], P=0.19). Hulisan Capsules + conventional treatment showed insignificant difference in symptom relief rate from the Zhuifeng Tougu Capsules + conventional treatment(RR=1.07, 95%CI[0.91, 1.25], P=0.44). The Lequesne score was insignificantly different between Hulisan Capsules + conventional treatment and conventional treatment/Zhuifeng Tougu Capsules + conventional treatment(MD=-2.17, 95%CI[-6.29, 1.96], P=0.30). The incidence of adverse reactions in the experimental group was significantly lower than control group(RR=0.57, 95%CI[0.34, 0.96], P=0.03). According to the available data and methods, Hulisan Capsules/Hulisan Capsules + conventional treatment could improve the symptom relief rate, Lysholm score, knee function score, and VAS score of patients with knee osteoarthritis, and alleviate the symptoms of pain, stiffness, and swelling of them. No serious adverse reactions were found yet. In the future, more large-sample and standard clinical trials are needed to verify the effect and safety of Hulisan Capsules in the treatment of knee osteoarthritis.
Humans ; Osteoarthritis, Knee/drug therapy* ; Capsules ; Pain