To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1β(IL-1β) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1β showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.
Rats ; Animals ; Chondrocytes ; Osteoarthritis, Knee/pathology* ; RNA, Circular/pharmacology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MicroRNAs/metabolism* ; Apoptosis ; Autophagy/genetics* ; Collagen/metabolism*

OBJECTIVE: To analyze the correlation between the expression of silencing information regulator 2 related enzyme 1 (SIRT1), tumor necrosis factor like weak inducer of apoptosis (TWEAK) and knee osteoarthritis. METHODS: Total of 103 patients with knee joint (knee osteoarthritis group) from February 2019 to August 2021 were selected including 40 males and 63 females with an average age of (62.02±6.09) years;according to the modified Mankin score, 103 patients were divided into mild group (Mankin score 1-4 points, 31 cases) and moderate group (Mankin score 5-8 points, 40 cases) and severe group (Mankin score ≥9, 32 cases). Another 105 physical examination volunteers were selected as the control group including 46 males and 59 females with an average age of (62.11±6.34) years old. The levels of SIRT1 and TWEAK in articular effusion and serum were detected in the knee osteoarthritis group, while serum SIRT1 and TWEAK were detected in the control group only. The relationship between SIRT1, TWEAK and the occurrence and disease of knee osteoarthritis were analyzed. RESULTS: Articular cavity fluid TWEAK, serum TWEAK, CRP, IL-6, IL-1β, white blood cell count and ESR were higher than those in the control group(P<0.05), articular cavity fluid SIRT1 and serum SIRT1 were lower than those in the control group(P<0.05). TWEAK level in the severe group was higher than that in the moderate and mild groups(P<0.05), SIRT1 was lower than that in the moderate and mild groups (P<0.05). The level of SIRT1 in articular cavity effusion was positively correlated with the serum level of SIRT1 (P<0.05), and negatively correlated with CRP, IL-6, IL-1β, white blood cell count, modified Mankin score and ESR (P<0.05). TWEAK level in articular cavity fluid was positively correlated with serum TWEAK level (P<0.05), C-reactive protein(CRP), interleukin(IL)-6, IL-1β, white blood cell count, modified Mankin score and erythrocyte sedimentation rate(ESR) (P<0.05). Body mass index, undertaking heavy physical work, and articular cavity fluid TWEAK were risk factors for the occurrence of knee osteoarthritis(P<0.05), and articular cavity fluid SIRT1 was a protective factor for the occurrence of knee arthritis (P<0.05). The area under curve(AUC) of SIRT1 and TWEAK for knee osteoarthritis was 0.641 and 0.653, and the AUC of SIRT1 and TWEAK for knee osteoarthritis was 0.879, which was higher than SIRT1 and TWEAK alone (z=6.105 and 6.225, P<0.05). CONCLUSION The level of SIRT1 in articular fluid in patients with knee arthritis is decreased and the level of TWEAK is increased. Low SIRT1 and high TWEAK are associated with the onset and exacerbation of knee osteoarthritis.
Aged ; Female ; Humans ; Male ; Middle Aged ; Apoptosis ; Interleukin-6 ; Osteoarthritis, Knee/pathology* ; Sirtuin 1/blood* ; Cytokine TWEAK/blood*

OBJECTIVE: To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis. METHODS: Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m^-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m^-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group. RESULTS: The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001). CONCLUSION Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.
Male ; Female ; Humans ; Osteoarthritis, Knee/diagnostic imaging* ; Bone Marrow/pathology* ; Case-Control Studies ; Bone Marrow Diseases/etiology* ; Osteoporosis/complications* ; Edema/etiology* ; Magnetic Resonance Imaging/methods*

OBJECTIVE: To investigate the relationship between bone marrow edema and pathological changes, symptoms and signs of severe knee osteoarthritis. METHODS: From January 2020 to March 2021, 160 patients with severe knee osteoarthritis who underwrent MRI of the knee at the Department of Bone and Joint, Wangjing Hospital, China Academy of Chinese Medical Sciences were included. Eighty patients with bone marrow edema were selected as the case group, including 12 males and 68 females, aged from 51 to 80 years old with an average of (66.58±8.10) years old, the duration of disease 5 to 40 months with an average of (15.61±9.25) months. Eighty patients without bone marrow edema were selected as the control group, including 15 males and 65 females, aged from 50 to 80 years old with an average of (67.82±8.05) years old, the duration of disease 6 to 37 months with an average of (15.75±8.18) months, BMI was (28.26±3.13) kg·m^-2 ranged from 21.39 to 34.46 kg·m^-2. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score (WORMS). The degree of knee osteoarthritis was evaluated by Kellgren- Lawrence(K-L) grade and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The degree of joint pain was evaluated by visual analogue scale(VAS) and WOMAC pain score, the joint signs were evaluated by tenderness, percussion pain, joint swelling and joint range of motion. To explore the relationship between bone marrow edema and knee osteoarthritis, the prevalence of bone marrow edema and K-L grade were compared between the two groups. Furthermore the WORMS score and WOMAC index, pain-related score, and sign-related score correlation coefficient were analyzed to further explore the relationship between bone marrow edema and knee osteoarthritis index, joint pain symptoms and signs. RESULTS: There was 68.75% (55/80) of the patients in the case group were in K-L grade Ⅳ, and 52.5% (42/80) in the control group, indicating a higher proportion of patients with grade Ⅳ in the case group than the control group (χ²=4.425, P<0.05). In the case group, there was a strong correlation between bone marrow edema WORMS score and knee osteoarthritis WOMAC index. (r=0.873>0.8, P<0.001), a moderate correlation between WORMS score and VAS score and WOMAC pain score(r=0.752, 0.650>0.5, P<0.001), a moderate correlation between WORMS score and percussion pain score (r=0.784>0.5, P<0.001), and a weak correlation between WORMS score and VAS and tenderness score, joint swelling score and joint range of motion score (r=0.194, 0.259, 0.296<0.3, P<0.001). CONCLUSION Our study suggests that severe knee osteoarthritis is associated with an increased risk of bone marrow edema. Bone marrow edema can also lead to knee osteoarthritis joint pain, with percussion pain being a positive sign, but tenderness, joint swelling and limitation of activity are not significantly related to bone marrow edema.
Male ; Female ; Humans ; Osteoarthritis, Knee/pathology* ; Bone Marrow/pathology* ; Knee Joint/diagnostic imaging* ; Bone Marrow Diseases/etiology* ; Pain/pathology* ; Arthralgia ; Edema/pathology*

BACKGROUND: The zone of calcified cartilage (ZCC) plays an important role in the pathogenesis of osteoarthritis (OA) but has never been imaged in vivo with magnetic resonance (MR) imaging techniques. We investigated the feasibility of direct imaging of the ZCC in both cadaveric whole knee specimens and in vivo healthy knees using a 3-dimensional ultrashort echo time cones (3D UTE-Cones) sequence on a clinical 3T scanner. METHODS: In all, 12 cadaveric knee joints and 10 in vivo healthy were collected. At a 3T MR scanner with an 8-channel knee coil, a fat-saturated 3D dual-echo UTE-Cones sequence was used to image the ZCC, following with a short rectangular pulse excitation and 3D spiral sampling with conical view ordering. The regions of interests (ROIs) were delineated by a blinded observer. Single-component T2* and T2 values were calculated from fat-saturated 3D dual-echo UTE-Cones and a Carr-Purcell-Meiboom-Gill (T2 CPMG) data using a semi-automated MATLAB code. RESULTS: The single-exponential fitting curve of ZCC was accurately obtained with R2 of 0.989. For keen joint samples, the ZCC has a short T2* ranging from 0.62 to 2.55 ms, with the mean ± standard deviation (SD) of 1.49 ± 0.66 ms, and with 95% confidence intervals (CI) of 1.20-1.78 ms. For volunteers, the short T2* ranges from 0.93 to 3.52 ms, with the mean ± SD of 2.09 ± 0.56 ms, and the 95% CI is 1.43 to 2.74 ms in ZCC. CONCLUSIONS The high-resolution 3D UTE-Cones sequence might be used to directly image ZCC in the human knee joint on a clinical 3T scanner with a scan time of more than 10 min. Using this non-invasive technique, the T2* relaxation time of the ZCC can be further detected.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Imaging, Three-Dimensional ; methods ; Knee Joint ; pathology ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Osteoarthritis ; diagnostic imaging

PURPOSE: The aim of this study was to analyze anatomical popliteal artery entrapment syndrome (PAES) and to individualize the treatment of this condition according to the anatomical status of the artery and the adjacent structure. METHODS: A total of 35 anatomical PAES legs in 23 consecutive patients treated within the Asan Medical Center, Seoul, Korea between 1995 and 2011 were analyzed retrospectively. Anatomical PAES was diagnosed by MRI and/or CT scans of the knee joint, and CT or conventional transfemoral arteriography of the lower extremities. RESULTS: We noted a type II gastrocnemius medial head (GNM) anomaly, a type III GNM anomaly, or an aberrant plantaris muscle in 51.4%, 20%, and 28.6% of PAES legs, respectively. In assessments of the arterial lesions, popliteal or tibial artery occlusion was noted in 19 of 26 symptomatic PAES legs. For cases without popliteal artery lesions, myotomy of the anatomically deranged muscle was performed in 5 of 7 symptomatic and 4 of 9 asymptomatic PAES legs. For occluded popliteal arteries, we performed ten direct repairs of the pathological popliteal artery and 4 femoro-below the knee popliteal bypass surgeries. As a result of the arterial Surgery, 9 direct procedures with myotomy yielded a patent artery, while 3 graft failures were noted in the bypass group. The median follow-up period was 84 months (range, 12–206 months). CONCLUSION: We recommend that treatment of PAES should be individualized based on pathology, symptoms, and various imaging studies.
Angiography ; Arteries ; Chungcheongnam-do ; Follow-Up Studies ; Head ; Humans ; Knee ; Knee Joint ; Korea ; Leg ; Lower Extremity ; Magnetic Resonance Imaging ; Muscle, Skeletal ; Pathology ; Popliteal Artery* ; Retrospective Studies ; Seoul ; Tibial Arteries ; Tomography, X-Ray Computed ; Transplants

Anterior Cruciate Ligament ; pathology ; Anterior Cruciate Ligament Injuries ; Biomechanical Phenomena ; Foreign Bodies ; Humans ; Knee Joint ; pathology ; Tibia

BACKGROUND: Persistent pain after total knee arthroplasty (TKA) is dissatisfying to the patient and frustrating to the surgeon. The purpose of this study is to evaluate the aseptic causes and clinical course of intractable pain following TKA. METHODS: Of the total 2,534 cases of primary TKA reviewed, 178 cases were classified as having aseptic persistent pain that was not resolved within 1 year after surgery. Except for the cases with periprosthetic fracture (56 knees), 122 cases of aseptic painful TKA were divided into two groups: intra-articular group (83 knees) and extra-articular group (39 knees). RESULTS: In the intra-articular group, the main reasons for pain were aseptic loosening (n = 40), polyethylene wear (n = 16), instability (n = 10), recurrent hemarthrosis (n = 5), patellar maltracking (n = 4), tendon ruptures (n = 4), and stiffness (n = 2). In the extraarticular group, 10 knees (25.6%) were found to have nerve entrapment in the spine, 6 knees (15.4%) were found to have hip osteoarthritis or femoral head avascular necrosis. The reasons for persistent knee pain in the remaining 23 knees (59.0%) still remain elusive. CONCLUSIONS: Persistent pain after TKA originated from pathology of extra-articular origin in a considerable number of cases in this study. Therefore, it is important to perform thorough preoperative evaluations to reduce pain resulting from extra-articular causes. Furthermore, meticulous surgical procedures and optimal alignment are required to reduce pain of intra-articular origin related to implant wear, instability, and patellar maltracking.
Arthroplasty, Replacement, Knee* ; Chronic Pain ; Head ; Hemarthrosis ; Humans ; Knee ; Necrosis ; Nerve Compression Syndromes ; Osteoarthritis, Hip ; Pain, Intractable ; Pathology ; Periprosthetic Fractures ; Polyethylene ; Rupture ; Spine ; Tendons

BACKGROUNDNumerous studies have investigated the influence of osseous factors on patellofemoral joint instability, but research on the influence of dynamic muscle factors in vivo is still in the exploratory stage. This study aimed to use magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to evaluate vastus medialis oblique (VMO) fiber bundles in patients with recurrent patellar dislocation to explore the changes in muscle morphology and function.

METHODSThis prospective study involved 30 patients (7 males and 23 females; average age, 21.4 ± 3.8 years) clinically diagnosed with recurrent patellar dislocation in Peking University Third Hospital and 30 healthy volunteers matched for age, sex, and body mass index in our medical school between January 2014 and October 2014. None of the patients had a recent history of traumatic patellar dislocation or transient patellar dislocation. All patients underwent conventional MRI and DTI of the knee. The cross-sectional area of the VMO on MRI and the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and primary (λ1), secondary (λ2), and three-level characteristic (λ3) values on DTI were measured. The independent-samples t-test was used to compare these parameters between the two groups.

RESULTSCompared with the control group, the patient group showed significantly higher FA values (0.39 ± 0.05 vs. 0.33 ± 0.03) and significantly lower ADC (1.51 ± 0.13 vs. 1.58 ± 0.07), λ2 (4.96 ± 0.13 vs. 5.04 ± 0.07), and λ3 values (4.44 ± 0.14 vs. 4.58 ± 0.07; t = 5.99, t = -2.58, t = -3.02, and t = -4.88, respectively; all P < 0.05). Cross-sectional VMO area and λ1 values did not differ between the two groups (t = -1.82 and t = 0.22, respectively; both P > 0.05).

CONCLUSIONSThe functional status of the VMO is closely associated with recurrent patellar dislocation. MRI, especially DTI (FA, ADC, λ2, and λ3), can detect early changes in VMO function and might facilitate the noninvasive monitoring of the functional status of the VMO in patients with recurrent patellar dislocation.

Adolescent ; Adult ; Child ; Diffusion Tensor Imaging ; methods ; Female ; Humans ; Knee Joint ; pathology ; Magnetic Resonance Imaging ; Male ; Patella ; pathology ; Patellar Dislocation ; diagnosis ; Prospective Studies ; Quadriceps Muscle ; pathology ; Sensitivity and Specificity ; Young Adult

An unusual grayish brown discoloration of the synovium was found during a knee arthroscopy of a 72-year-old man. He also had similar pigmentation affecting the skin on the legs, arms, hands, and face. It was found he had been taking 400 mg of amiodarone hydrochloride daily for last 7 years. Amiodarone is known to cause a slate grey pigmentation of skin and cornea, but we believe this is the first report of amiodarone-induced pigmentation of the synovium. The arthroscopist should be aware of the possibility of drug-related synovial pigmentation and include this in differential diagnosis.
Aged ; Amiodarone/*adverse effects/therapeutic use ; Anti-Arrhythmia Agents/*adverse effects/therapeutic use ; Arrhythmias, Cardiac/complications/drug therapy ; Arthroscopy ; Diagnosis, Differential ; Humans ; Knee Joint/surgery ; Male ; Pigmentation Disorders/*chemically induced/*diagnosis ; Skin/pathology ; Synovial Membrane/*pathology