1.Assessment of depression among elderly patients with knee and hip osteoarthritis in a tertiary hospital in the Philippines: A cross-sectional study
The Filipino Family Physician 2025;63(1):2-7
BACKGROUND
Osteoarthritis (OA) is a leading cause of pain and disability among older adults, often accompanied by mental health issues like depression. Understanding the impact of clinico-sociodemographic factors on OA and depression is essential for improving patient outcomes.
OBJECTIVEThis study aimed to examine the association between osteoarthritis, clinico-sociodemographic factors and depression among elderly patients in a tertiary hospital setting.
METHODSA cross-sectional study was conducted on elderly patients with osteoarthritis to explore the correlation between clinico-sociodemographic factors and the severity of depression. Data were collected and analyzed using Microsoft Excel 2018, with descriptive and inferential statistics, including Chi-square tests and correlation analyses (Spearman’s Rank for WOMAC scores and Geriatric Depression Scale, Pearson’s for socio-demographic factors and comorbidities).
RESULTSDespite most participants (48.15%) having normal depression scores, a significant number (37.04%) had mild depression and 14.81% had moderate depression. Knee pain was the most common affected area (56.79%), and 62.96% had one comorbidity. Albeit having no statistically significant correlations, positive weak relationships were identified between socio-demographic factors, clinical status and depression.
CONCLUSIONThis study identified weak associations between osteoarthritis-related pain and depression, especially among individuals with comorbidities and higher pain levels. While socio-demographic factors may influence the severity of both osteoarthritis and depression, further research is necessary to explore these relationships more thoroughly and to consider additional contributing factors. These findings underscore the importance of integrated care approaches that address both the physical and mental health needs of elderly patients with osteoarthritis.
Human ; Osteoarthritis ; Depression
2.Internal heat acupuncture therapy for 44 cases knee osteoarthritis of early to middle stages.
Jiawei LIAN ; Zheying LAI ; Jianfeng XU ; Ruizhu LIN
Chinese Acupuncture & Moxibustion 2025;45(1):27-30
OBJECTIVE:
To observe the clinical effect of internal heat acupuncture therapy for knee osteoarthritis of early to middle stages, and explore its influence on cartilage thickness.
METHODS:
A total of 44 patients with knee osteoarthritis of early to middle stages were treated with internal heat acupuncture therapy at ashi points (most of them are located at the subpatellar fat pad, both sides of the patellar ligament, the tendon of the quadriceps and the attachment of the medial and lateral collateral ligaments), once a week, a total of 4 weeks of treatment. Before and after treatment, after 3 months of treatment completion (in the follow-up), the visual analogue scale (VAS) score, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, frequency of 30-second chair stand test (30sCST), cartilage thickness of femoral intercondylar and knee joint ultrasound score were compared, and the clinical effect was evaluated.
RESULTS:
After treatment, the VAS、WOMAC and knee joint ultrasound scores were reduced (P<0.05), frequency of 30sCST was increased (P<0.05) compared with those before treatment; in the follow-up, the VAS、WOMAC scores were reduced (P<0.05), frequency of 30sCST and cartilage thickness of femoral intercondylar were increased (P<0.05) compared with those before treatment. After treatment, the total effective rate was 93.2% (41/44), in the follow-up, the total effective rate was 95.5% (42/44).
CONCLUSION
Internal heat acupuncture therapy is effective in the treatment of knee osteoarthritis of early to middle stages, could relieve the pain, improve the joint function, and delay cartilage degeneration and disease progression.
Humans
;
Osteoarthritis, Knee/physiopathology*
;
Male
;
Female
;
Middle Aged
;
Acupuncture Therapy
;
Aged
;
Treatment Outcome
;
Adult
;
Acupuncture Points
3.Research progress of effect mechanism of acupotomy for knee osteoarthritis.
Wenying YU ; Jing LIU ; Hong LIU ; Liangzhi ZHANG ; Zehao LIN ; Zhongbiao XIU
Chinese Acupuncture & Moxibustion 2025;45(6):867-874
Acupotomy therapy demonstrates the definite clinical efficacy on knee osteoarthritis (KOA). After reviewing systematically the mechanism studies on acupotomy for KOA over the past 5 years, It is revealed that acupotomy synergistically intervenes in the pathological progression of KOA through multi-target approaches, such as regulating cartilage homeostasis, restoring skeletal muscle function, alleviating synovial inflammatory responses, remodeling subchondral bone, and neuromodulation. But the current research still limits to single-tissue phenotypic observation, and is insufficiency in the in-depth exploration of multi-tissue synergistic interactions and molecular upstream-downstream regulatory mechanisms. Future studies should focus on the inheritance and innovation of acupotomy theory, and integrating multi-omics analytical technologies, artificial intelligence, and novel biochemical detection methods. The mechanism research targets on the interaction mechanisms among tissues, direct effects of acupotomy, immune-inflammatory regulatory mechanisms, and analgesic mechanisms, so as to comprehensively elucidate the therapeutic mechanism of acupotomy for KOA.
Humans
;
Acupuncture Therapy
;
Osteoarthritis, Knee/genetics*
;
Animals
4.Effect of acupuncture on chondrocyte autophagy in rats of knee osteoarthritis based on PI3K/Akt/mTOR signaling pathway.
Dekun LI ; Changfeng YAO ; Ziliang SHAN ; Zheng ZHOU ; Xianji ZHANG ; Kewen WANG ; Shaolin DU
Chinese Acupuncture & Moxibustion 2025;45(10):1459-1467
OBJECTIVE:
To observe the effect of acupuncture on chondrocyte autophagy in rats of knee osteoarthritis (KOA) and explore its underlying mechanisms.
METHODS:
Forty male SPF-grade SD rats were randomized into a blank group, a model group, a suspension group, an acupuncture group, and a combined therapy group, 8 rats in each one. Except the blank group, KOA model was prepared by the injection with papain. The suspension exercise therapy (10 min each time, three times daily), acupuncture (at "Yanglingquan" [GB34], "Zusanli" [ST36], and "Dubi" [ST35] on the right side, 30 min each intervention, once daily) and the combined therapy (the suspension exercise therapy combined with acupuncture) were delivered in the suspension group, the acupuncture group and the combined therapy group, respectively. The intervention of each group was performed continuously for 6 days, and 4 consecutive weeks, at the interval of 1 day. Before and after intervention, Lequesne MG score was assessed in the rats. After intervention, HE staining was adopted to observe the cartilaginous tissue morphology of the right knee joints, and Mankin score was evaluated; the serum levels of interleukin (IL)-1β, IL-6, and tumor neurosis factor-α (TNF-α) were measured using ELISA; the real-time PCR was provided to determine the mRNA expression of collagen protein type Ⅱ(COL2), collagen protein type Ⅹ (COL10), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), and autophagy-regulated protein (Beclin-1) in the cartilaginous tissue of the right knee joint; Western blot was employed to detect the protein expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR) and Beclin-1 in the cartilaginous tissue of the right knee joint.
RESULTS:
Compared with the blank group, the rats in the model group showed the higher Lequesne MG score (P<0.01), thinner cartilage of the right knee, reduced chondrocytes and disordered arrangement, and higher Mankin score (P<0.01). Besides, in the model group, the serum levels of IL-1β, IL-6 and TNF-α were elevated (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 decreased (P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR increased (P<0.01) in the cartilaginous tissue of the right knee joint. Compared with the model group, in the suspension group, the acupuncture group and the combined therapy group, the Lequesne MG scores were reduced (P<0.01), the cartilage of the right knee was thickened, the arrangement of chondrocytes was improved, and the Mankin scores were lower (P<0.01). Besides, in these intervention groups, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.01), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05, P<0.01), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint. When compared with the suspension group and the acupuncture group, in the combined therapy group, the Lequesne MG score was reduced (P<0.01), and the Mankin score was reduced (P<0.05, P<0.01). Besides, the serum levels of IL-1β, IL-6 and TNF-α were reduced (P<0.05), the mRNA expression of COL2 and Beclin-1 and the protein expression of Beclin-1 increased (P<0.05), the mRNA expression of COL10, PI3K, Akt and mTOR, and the protein expression of p-PI3K, p-Akt and p-mTOR decreased (P<0.05, P<0.01) in the cartilaginous tissue of the right knee joint.
CONCLUSION
Acupuncture can promote cartilage regeneration of knee joint and autophagy in KOA rats, alleviate inflammation, so as to retard cartilage degeneration, which may be possibly associated with the PI3K/Akt/mTOR signaling pathway.
Animals
;
Male
;
Acupuncture Therapy
;
Proto-Oncogene Proteins c-akt/genetics*
;
TOR Serine-Threonine Kinases/genetics*
;
Osteoarthritis, Knee/physiopathology*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Rats
;
Signal Transduction
;
Rats, Sprague-Dawley
;
Chondrocytes/metabolism*
;
Humans
;
Autophagy
;
Acupuncture Points
5.Acupuncture combined with blade needle therapy for knee osteoarthritis:a randomized controlled trial.
Xiao LI ; Yujie CUI ; Wenjin YANG ; Yuanyuan LI ; Xiao GUO ; Di LIU ; Mengyun YU ; Hui HU ; Hua LI
Chinese Acupuncture & Moxibustion 2025;45(11):1571-1576
OBJECTIVE:
To observe the clinical efficacy and safety of acupuncture combined with blade needle therapy for 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. The control group received acupuncture at Neixiyan (EX-LE4),Dubi (ST35), Yinlingquan (SP9), Liangqiu (ST34), Xuehai (SP10), Yanglingquan (GB34) and Zusanli (ST36) on the affected side, once every other day, 3 times a week. The observation group received blade needle therapy on the basis of the treatment in the control group, once every 3 days, 2 times a week. Both groups were treated for 4 weeks. Before treatment, after 2, 4 weeks of treatment, and after 1 month of treatment completion (in follow-up), the scores of pain visual analogue scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and Lequesne index were observed in the two groups, and the clinical efficacy and safety were evaluated.
RESULTS:
After 2, 4 weeks of treatment and in follow-up, the pain VAS scores, Lequesne index scores, and pain, stiffness, function scores of WOMAC in both groups were decreased compared with those before treatment (P<0.05), and the VAS scores, Lequesne index scores and pain, function scores of WOMAC in the observation group were lower than those in the control group (P<0.05). The effective response rate in the observation group was 76.7% (23/30), while that in the control group was 70.0% (21/30), there was no statistically significant difference in the effective response rates between the two groups (P>0.05). No adverse reactions were observed in either group.
CONCLUSION
Acupuncture combined with blade needle therapy could alleviate pain and promote functional recovery in KOA patients, and achieve long-lasting improvements.
Humans
;
Osteoarthritis, Knee/physiopathology*
;
Acupuncture Therapy/instrumentation*
;
Male
;
Female
;
Middle Aged
;
Aged
;
Acupuncture Points
;
Treatment Outcome
;
Adult
;
Needles
;
Combined Modality Therapy
6.Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.
Kuanyu XIA ; Lang MIN ; Wenqing XIE ; Guang YANG ; Dong Keon YON ; Seung Won LEE ; Ai KOYANAGI ; Louis JACOB ; Lee SMITH ; Jae Il SHIN ; Masoud RAHMATI ; Wenfeng XIAO ; Yusheng LI
Chinese Medical Journal 2025;138(13):1568-1577
BACKGROUND:
The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.
METHODS:
PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.
RESULTS:
Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.
CONCLUSIONS
In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans
;
Arthroplasty, Replacement, Knee/methods*
;
Osteoarthritis, Knee/surgery*
;
Randomized Controlled Trials as Topic
;
Treatment Outcome
7.Key roles of the superficial zone in articular cartilage physiology, pathology, and regeneration.
Li GUO ; Pengcui LI ; Xueqin RONG ; Xiaochun WEI
Chinese Medical Journal 2025;138(12):1399-1410
The superficial zone (SFZ) of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli. The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis (OA) cartilage degeneration and a major site of cartilage progenitor cells, suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA. However, to date, SFZ research has not received sufficient attention, accounting for only about 0.58% of cartilage tissue research. The structure, biological composition, function, and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear. This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA, aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage, hoping that scholars will give more attention to the SFZ of articular cartilage in the future.
Cartilage, Articular/pathology*
;
Humans
;
Regeneration/physiology*
;
Animals
;
Osteoarthritis/physiopathology*
8.Correlation between severity of knee joint osteoarthritis and alignment of patellofemoral and patellar height on radiographs.
Zhenlei YANG ; Mingjie SHEN ; Deshun XIE ; Junzhe ZHANG ; Qingjun WEI
Chinese Medical Journal 2025;138(8):947-952
BACKGROUND:
The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs.
METHODS:
This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants' demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables.
RESULTS:
The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity ( r = 0.516, P <0.01), whereas LPTA showed a strong negative correlation ( r = -0.662, P <0.01). Additionally, SA ( r = 0.616, P <0.05), and TT-TG showed a strong positive correlation ( r = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = -2.946, P <0.001) and side (β = -0.839, P = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = -0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = -0.326, P = 0.041), body mass index (β = -0.061, P = 0.017) and age (β = -0.025, P <0.001) was associated with TT-TG.
CONCLUSION
Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.
Humans
;
Female
;
Male
;
Osteoarthritis, Knee/pathology*
;
Middle Aged
;
Retrospective Studies
;
Aged
;
Patellofemoral Joint/pathology*
;
Magnetic Resonance Imaging
;
Adult
;
Patella/pathology*
;
Radiography
9.EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis.
Yang CHEN ; Shanshan DONG ; Xin ZENG ; Qing XU ; Mingwei LIANG ; Guangneng LIAO ; Lan LI ; Bin SHEN ; Yanrong LU ; Haibo SI
Chinese Medical Journal 2025;138(1):79-92
BACKGROUND:
Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported.
METHODS:
The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats.
RESULTS:
Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis.
CONCLUSIONS
A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics*
;
Osteoarthritis, Knee/pathology*
;
Chondrocytes/metabolism*
;
Pyroptosis/physiology*
;
HMGB1 Protein/genetics*
;
MicroRNAs/metabolism*
;
Endoplasmic Reticulum Stress/genetics*
;
Humans
;
Animals
;
Rats
;
Male
;
Rats, Sprague-Dawley
;
Middle Aged
10.Kaempferide inhibited progression of osteoarthritis by targeting the HIF-1 signaling pathway.
Xianjie WEI ; Hesuyuan HUANG ; Ping YUAN ; Peisen XIE ; Keshi ZHANG ; Zhenpeng GUAN
Chinese Medical Journal 2025;138(21):2813-2823
BACKGROUND:
Osteoarthritis (OA) is a prevalent joint disorder that significantly impairs quality of life among elderly individuals because of chronic pain and physical disability. As the global burden of OA continues to rise, novel therapeutic strategies are urgently needed. Kaempferide (KA), a flavonoid derived from traditional Chinese herbal medicine, is known for its anti-inflammatory properties. However, the effect of KA on the progression of OA has not been well investigated. This study aimed to explore the therapeutic potential of KA in an OA model and investigate the underlying mechanisms via transcriptomic sequencing.
METHODS:
An in vitro OA model was established using SW1353 cells treated with interleukin-1 beta (IL-1β) and different concentrations of KA (30, 60, or 90 μmol/L) for 24 h. The anti-inflammatory effects of KA were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting. In vivo , a papain-induced OA rat model was used to evaluate the therapeutic effects of KA through histological and behavioral analyses. Transcriptomic sequencing was performed to explore the differentially expressed genes (DEGs) and related signaling pathways. Statistical analysis was conducted using one-way analysis of variance.
RESULTS:
KA significantly increased cell viability in the OA chondrocyte model and downregulated the expression of inflammatory cytokines and cartilage degradation markers, with the greatest reduction observed at 90 μmol/L. In vivo , KA treatment mitigated cartilage degradation and improved gait behavior in OA rats. Transcriptomic analysis revealed substantial modulation of DEGs, implicating the hypoxia-inducible factor-1 (HIF-1) signaling pathway as a key mechanism. Further blocking and rescue experiments revealed that KA regulated key molecules within the HIF-1 pathway, specifically interferon-gamma (IFN-γ) and hypoxia-inducible factor 1-alpha (HIF-1α), confirming their critical roles in mediating the therapeutic effects of KA.
CONCLUSION
KA inhibited the progression of OA by targeting the HIF-1 signaling pathway, reducing inflammation, and cartilage degradation.
Animals
;
Osteoarthritis/metabolism*
;
Signal Transduction/drug effects*
;
Rats
;
Rats, Sprague-Dawley
;
Humans
;
Male
;
Hypoxia-Inducible Factor 1/metabolism*
;
Interleukin-1beta


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