T staging esophageal tumors with x rays.

With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor T staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment.

Effectiveness of Computerized Cognitive Training on Working Memory in Pediatric Cancer Survivors: A Systematic Review and Meta-analysis.

BACKGROUND: Interactive features of computerized cognitive training (CCT) may enhance adherence to training, providing a relatively low-cost intervention. A robust systematic review on the effectiveness of CCT for improving working memory (WM) among pediatric survivors with cancer is lacking. OBJECTIVE: To summarize the available evidence and determine the effectiveness of CCT for WM among pediatric survivors with cancer. INTERVENTIONS/METHODS: Five databases were searched. The Effective Public Health Practice Project was used to assess the study quality. ReviewerManager was used. The primary outcome was WM performance. Secondary outcomes included processing speed, attention, intervention adherence, and number of adverse events. RESULTS: Six studies were included. Regarding overall quality, 1 study was weak, and 5 studies were moderate. Five studies reported a significant improvement of WM postintervention (P < .05). The meta-analysis of Cogmed interventions on symbolic WM revealed a significant difference between groups (vs placebo), with an overall pooled effect size of 0.71 (95% confidence interval, 0.02-1.41; P = .04). Two and 4 studies investigated the effects of CCT on processing speed and attention, respectively, with conflicting results. Four studies reported adherence of 80% or greater. Two studies reported no adverse events. CONCLUSIONS: Computerized cognitive training using Cogmed has a significant positive effect on WM. The effects of CCT on processing speed and attention remain inconclusive. IMPLICATIONS FOR PRACTICE: More rigorous trials should be conducted to elucidate the cognitive effects of CCT, particularly processing speed and attention, in the pediatric population with cancer. Further studies should consider combining CCT with other existing interventions to strengthen their effectiveness.

Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5-a]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease.

Dry eye disease (DED) is one of the most prevalent ocular diseases but has limited treatment options. Cystic fibrosis transmembrane conductance regulator (CFTR), a major chloride channel that stimulates fluid secretion in the ocular surface, may pave the way for new therapeutic strategies for DED. Herein, we report the optimization of Cact-3, a potent CFTR activator with poor solubility, to 16d, a potent CFTR activator with suitable solubility for eye drop formulation. Notably, 16d was well distributed in target tissues including cornea and conjunctiva with minimal systemic exposure in rabbit. Topical ocular instillation of 16d significantly enhanced tear secretion and improved corneal erosion in a mouse model of DED. In addition, 16d significantly reduced mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-17, and TNF-α and MMP2 in cornea and conjunctiva of DED mice.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

Novel CFTR Activator Cact-3 Ameliorates Ocular Surface Dysfunctions in Scopolamine-Induced Dry Eye Mice.

Cystic fibrosis transmembrane conductance regulator (CFTR) is highly expressed on the ocular epithelium and plays a pivotal role in the fluid secretion driven by chloride transport. Dry eye disease is one of the most common diseases with limited therapeutic options. In this study, a high-throughput screening was performed to identify novel CFTR activators capable of inducing chloride secretion on the ocular surface. The screening of 50,000 small molecules revealed three novel CFTR activators. Among them, the most potent CFTR activator, Cact-3 (7-(3,4-dimethoxyphenyl)-N-(4-ethoxyphenyl)pyrazolo [1,5-α]pyrimidine-2-carboxamide), produced large and sustained Cl- currents in WT-CFTR-expressing FRT cells with no alterations of ANO1 and hERG channel activity. The application of Cact-3 strongly activated CFTR in the ocular epithelia of mice and it also significantly increased CFTR-mediated Cl- transport in a primary cultured human conjunctival epithelium. Cact-3 strongly stimulated tear secretion in normal mice. In addition, Cact-3 significantly reduced ocular surface damage and the expression of proinflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in an experimental mouse model of dry eye disease. These results suggest that Cact-3, a novel CFTR activator, may be a potential development candidate for the treatment of dry eye disease.

Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of ß-catenin.

Vestibular schwannoma (VS), one of characteristic tumors of neurofibromatosis type 2 (NF2), is an intracranial tumor that arises from Schwann cells of the vestibular nerve. VS results in hearing loss, tinnitus, dizziness, and even death, but there are currently no FDA-approved drugs for treatment. In this study, we established a high-throughput screening to discover effective compounds that could inhibit the viability of VS cells. Among 1019 natural products from the Korea Chemical Bank screened, we found that celastrol, a pentacyclic triterpene derived from a Tripterygium Wilfordi plant, exerted potent inhibitory effect on the viability of VS cells with an IC50 value of 0.5 µM. Celastrol (0.5, 1 µM) dose-dependently inhibited the proliferation of primary VS cells derived from VS patients. Celastrol also inhibited the growth, and induced apoptosis of two other VS cell lines (HEI-193 and SC4). Aberrant activation of Wnt/ß-catenin signaling has been found in VS isolated from clinically defined NF2 patients. In HEI-193 and SC4 cells, we demonstrated that celastrol (0.1, 0.5 µM) dose-dependently inhibited TOPFlash reporter activity and protein expression of ß-catenin, but not mRNA level of ß-catenin. Furthermore, celastrol accelerated the degradation of ß-catenin by promoting the formation of the ß-catenin destruction complex. In nude mice bearing VS cell line SC4 allografts, administration of celastrol (1.25 mg · kg-1 · d-1, i.p. once every 3 days for 2 weeks) significantly suppressed the tumor growth without showing toxicity. Collectively, this study demonstrates that celastrol can inhibit Wnt/ß-catenin signaling by promoting the degradation of ß-catenin, consequently inhibiting the growth of VS.

Utilization of the Youth Quitline as an opportunity for an undergraduate nursing students to deliver smoking cessation counseling as their clinical placement: An implementation of a service-learning model.

BACKGROUND: Smoking is an important modifiable risk factor of morbidities and mortality. Although healthcare professionals play an important role in smoking cessation, their adoption of such practices is relatively low because of inadequate training. To address this issue, we incorporated a service-learning model to operate the Youth Quitline. Undergraduate nursing students were trained and received supervision while delivering smoking cessation counseling through the Youth Quitline as their clinical placement. OBJECTIVES: We evaluated the effectiveness of the placement by assessing students' knowledge, attitudes and practices regarding smoking cessation and tobacco control. DESIGN: One-group pretest-posttest design. SETTING: Youth Quitline. PARTICIPANTS: A total of 61 third-year students in a mental health nursing program. METHODS: Students were required to complete 80 h at the Youth Quitline. The 80 h were divided into 20 sessions; students used four sessions to approach and recruit youth smokers in the community, then provided them with telephone counseling for the rest of the time. Prior to the placement, students attended a 2-day workshop. The outcomes were changes in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control 3 months after the placement compared with baseline. RESULTS: From January-June 2021, students conducted 105 outreach activities to identify 3142 smokers in the community, and provided telephone counseling for 336 smokers via Youth Quitline. Compared with baseline, significant improvements were observed in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control at 3-month follow-up. CONCLUSIONS: The clinical placement improved students' knowledge, attitudes and practices regarding smoking cessation and tobacco control, enhancing their competency in providing support to assist smokers to quit in their future practice. Incorporating the service-learning model in existing community-based services can provide additional venues for nursing students to practice. This is particularly important because many venues have restricted access during the COVID-19 pandemic.

Sleep disruption and its contributing factors in Chinese survivors of childhood cancer: A cross-sectional study.

OBJECTIVES: This study provided information about sleep disruption, particularly its prevalence and severity among Hong Kong Chinese childhood cancer survivors. Additionally, we identified the factors influencing sleep disruption and explored how fatigue, depressive symptoms and physical activity (PA) affect sleep disruption. METHODS: Four hundred two survivors 6-18 years old and 50 age- and gender-matched healthy counterparts were assessed for depressive symptoms, fatigue, PA and subjective sleep quality. Demographic and clinical information were collected. Multiple logistic regression analyses were conducted to identify any factors contributing to poor sleep. RESULTS: Mean scores of depressive symptoms, fatigue for children and that for adolescents, and PA in survivors were 16.1 (SD = 11.1), 24.6 (SD = 10.3), 27.7 (SD = 7.8), and 3.08 (SD = 2.9), respectively. 44.8% of the survivors were poor sleepers, which was more that in healthy counterparts. The three most common sleep problem were prolonged sleep latency (31.9%), daytime dysfunction (23.4%), and sleep disturbance (22.9%). The time since last treatment (children: AOR = 0.54, 95% CI = 0.30-0.96, p = 0.04; adolescents: AOR = 0.80, 95% CI = 0.70-0.92, p < 0.01) and PA levels (children: AOR = 0.46, 95% CI = 0.260-0.82, p = 0.01; adolescents: AOR = 0.70, 95% CI = 0.49-0.98, p = 0.04) were negatively associated with sleep disruption, while depressive symptoms (children: AOR = 1.31, 95% CI = 1.04-1.64, p = 0.02; adolescents: AOR = 1.07, 95% CI = 1.01-1.13, p = 0.03), fatigue (children: AOR = 1.15, 95% CI = 1.00-1.31, p = 0.04; adolescents: AOR = 1.08, 95% CI = 1.02-1.15, p = 0.01), number of treatment received (children: AOR = 16.56, 95% CI = 1.27-216.82, p = 0.03; adolescents: AOR = 7.30, 95% CI = 2.36-22.56, p < 0.01), and co-sleeping (children: AOR = 29.19, 95% CI = 1.65-511.57, p = 0.02; adolescents: AOR = 4.63, 95% CI = 1.22-17.61, p = 0.02) were positively associated with sleep disruption. CONCLUSION: Physical activity made the largest contribution to reduce sleep disruption. It is crucial to advocate for the adoption and maintenance of PA in survivorship.

PATHOLOGIC FINDINGS IN GENDER-AFFIRMING MASTECTOMY: A SYSTEMATIC REVIEW.

Following increased cultural awareness, expanded access to care, and decreased stigmatization, the number of transgender individuals seeking gender affirmation surgery such as gender-affirmation mastectomy (GAM) continues to rise. While post-mastectomy breast tissue is often sent for pathologic evaluation, few studies address the utility and standardization of this practice. This literature review evaluates the pathology findings in GAM specimens reported in the medical literature. A systematic review following PRISMA guidelines was performed to evaluate all medical publications related to pathology reports following GAM. The overall type and incidence of benign and malignant breast lesions were analyzed to elucidate which patient characteristics significantly affect the pathology findings. Overall, eight of 488 identified studies met inclusion criteria (1278 patients). The incidence of pre-malignant lesions was 2.42%, including flat epithelial atypia (0.08%), atypical hyperplasia (0.23%), atypical ductal hyperplasia (1.33%), atypical lobular hyperplasia (0.39%), and lobular carcinoma in situ (0.39%).Patient age, hormonal therapy, and family / patient history of breast cancer were inconsistently reported among included studies. Lack of standardized pathologic classification did not permit further statistical analysis. Although patients who undergo GAM are unlikely to have premalignant or malignant findings on breast pathology examination, pathologic evaluation of breast tissue remains common practice. Additional studies, which include a standardized method of pathologic evaluation, are necessary before practice guidelines can be recommended.

Psychometric properties of the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) among Hong Kong Chinese childhood cancer survivors.

BACKGROUND: Sleep disruption is a prevalent symptom reported by survivors of childhood cancer. However, there is no validated instrument for assessing this symptom in this population group. To bridge the literature gap, this study translated and adapted the Pittsburgh Sleep Quality Index (PSQI) for Hong Kong Chinese cancer survivors and examined its psychometric properties and factor structure. METHODS: A convenience sample of 402 Hong Kong Chinese childhood cancer survivors aged 6-18 years were asked to complete the Chinese version of the PSQI, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Fatigue Scale-Child (FS-C)/Fatigue Scale-Adolescent (FS-A), and Pediatric Quality of Life Inventory (PedsQL). To assess known-group validity, 50 pediatric cancer patients and 50 healthy counterparts were recruited. A sample of 40 children were invited to respond by phone to the PSQI 2 weeks later to assess test-retest reliability. A cutoff score for the translated PSQI used with the survivors was determined using receiver operating characteristic analysis. RESULTS: The Chinese version of the PSQI had a Cronbach alpha of 0.71, with an intraclass correlation coefficient of 0.90. Childhood cancer survivors showed significantly lower mean PSQI scores than children with cancer, and significantly higher mean scores than healthy counterparts. This reflected that childhood cancer survivors had a better sleep quality than children with cancer, but a poorer sleep quality than healthy counterparts. We observed positive correlations between PSQI and CES-DC scores and between PSQI and FS-A/FS-C scores, but a negative correlation between PSQI and PedsQL scores. The results supported that the Chinese version of the PSQI showed convergent validity. Confirmatory factor analysis showed that the translated PSQI data best fit a three-factor model. The best cutoff score to detect insomnia was 5, with a sensitivity of 0.81 and specificity of 0.70. CONCLUSION: The Chinese version of the PSQI is a reliable and valid instrument to assess subjective sleep quality among Hong Kong Chinese childhood cancer survivors. The validated PSQI could be used in clinical settings to provide early assessments for sleep disruption. Appropriate interventions can therefore be provided to minimize its associated long-term healthcare cost. Trial registration This study was registered in ClinicalTrials.gov with the reference number NCT03858218.

Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice.

Dry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1ß, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.

Can we recommend surgical treatment to the octogenarian with periampullary cancer?: National database analysis in South Korea.

BACKGROUND: The incidence of periampullary cancer in the elderly is increasing. Safety and oncologic effectiveness of pancreaticoduodenectomy in elderly patients is still controversial. MATERIALS AND METHODS: From 2002 to 2016, patients with periampullary cancer were evaluated. Customised health information data provided by the National Health Insurance Corporation (NHIS-2018-1-157) were used for analysis. Chronological changes in the incidence of periampullary cancer and long-term survival outcomes were estimated according to patients' age. RESULT: A total of 148,080 patients were found to have periampullary cancer. Chronologically, the incidence of periampullary cancer increased, and the proportion of elderly patients with periampullary cancer prominently increased (about 2.1 times in patients in their 70s and about 4.7 times in those older than 80 years). The number of patients with pylorus-preserving pancreaticoduodenectomy in their 70s (about 5.6 times, p < 0.001) and over 80 years of age (about 8.9 times, p < 0.001) was much higher than the number of patients aged younger than 50 years (about 1.7 times) and in their 60s (about 2.5 times). Long-term survival was different as per diagnosis (p < 0.001). In addition, it was observed that age was a factor attenuating the survival of patients with resected periampullary cancers (p < 0.001). However, in case of patients older than 80 years, those who underwent surgical treatment showed a higher survival rate than those who did not undergo surgical treatment. CONCLUSION: We can recommend surgical treatment for elderly patients with resectable periampullary cancer. The survival data in this study can be useful references especially in making treatment plan for octogenarians diagnosed with periampullary cancer.

Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma.

The median survival time of patients with glioblastoma is 14-16 months with a 5-year overall survival rate of 9.8%. Standard of care treatment includes radiation with concomitant temozolomide followed by cyclic temozolomide. If the patient develops myelosuppression (thrombocytopenia, leukopenia or anemia), the dose of temozolomide is reduced or stopped to avoid bleeding or infections. Recent studies have demonstrated that mild leukopenia is associated with increased overall survival in patients with glioblastoma. To confirm prior results showing that leukopenia is associated with increased overall survival as a primary outcome in patients with glioblastoma, the present study retrospectively collected complete blood counts from 141 patients with glioblastoma treated at the Beth Israel Deaconess Medical Center (Boston, USA) between January 2012 and December 2017. According to Kaplan-Meier analysis with a log-rank test, the presence of leukopenia was associated with increased overall survival (P=0.008). Furthermore, patients with grade 2 leukopenia (Common Terminology Criteria for Adverse Events version 5.0) survived longer than those without myelosuppression (P=0.024). There was no difference in overall survival between patients with grade 1, 3 or 4 leukopenia and those without myelosuppression. Leukopenia was associated with longer survival independent of age or extent of surgery in Cox proportional hazards regression modeling (P=0.00205). A possible interpretation is that grade 2 leukopenia is a biomarker of adequate temozolomide dosing in a population with diverse DNA repair function, which may be the consequence of variable O6-methylguanine-DNA methyltransferase activity. A prospective dose escalation trial is necessary to determine if treatment-induced leukopenia is beneficial for all patients receiving temozolomide.

Promoting physical activity among children with cancer through an integrated experiential training programme with coaching: A qualitative study.

OBJECTIVE: The study aim was to investigate how the integrated experiential training programme with coaching could motivate children undergoing cancer treatment to adopt and maintain physical activity. METHODS: A descriptive phenomenological approach was used. A purposive sample of 23 children and their parents participated in one-to-one 25-30-minute semistructured interviews. Interviews were tape-recorded and transcribed. Colaizzi's method of descriptive phenomenological data analysis was used. RESULTS: The integrated programme motivated children with cancer by increasing children's and parents' knowledge of physical activity, enhancing confidence in physical activity and improving physical and psychological well-being. Moreover, the programme provided children with encouragement and psychological support through coach companionship. The programme also facilitated children's participation in physical activity and modified perceptions of physical activity. CONCLUSION: This study addressed a gap in the literature by exploring how an integrated programme promoted and maintained physical activity in childhood cancer patients. PRACTICE IMPLICATIONS: The integrated experiential training programme is feasible and can be easily sustained. Future studies could extend the programme beyond aspects of physical activity to help people change their health practices and maintain a healthy lifestyle.

Molecular profiling of primary central nervous system lymphomas - predictive and prognostic value?

PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive variant of non-Hodgkin lymphoma. The diagnostic gold standard remains the pathologic review of tumor tissue mainly collected though biopsies. The majority of PCNSL are diffuse large B cell lymphoma (DLBCL). Biopsies are invasive procedures, and there have been efforts to develop minimally invasive diagnostic testing using serum and cerebral spinal fluid. This article reviews multiple markers that could potentially serve as future diagnostic tools and predictors of treatment response. RECENT FINDINGS: Many studies have attempted to classify DLBCL into different subtypes for prognostic purposes using methods such as immunohistochemistry. PCNSL often falls under the activated B-cell-like subgroup, and further genomic sequencing has identified alterations in genes within the B-cell receptor signaling axis at increased frequencies. Two such genes, MYD88 and CD79B, implicate the involvement of the NF-kB (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, and targeted agents to this pathway are currently being used in the treatment of relapsed/refractory PCNSL. SUMMARY: Although recent genomic profiling of PCNSL has increased the understanding of drivers in this disease and has also led to the introduction of targeted inhibitors, these markers have not yet been used for diagnostic and/or prognostic purposes. Further studies will need to evaluate if they hold great diagnostic potential.

Intra-articular injection of magnesium chloride attenuates osteoarthritis progression in rats.

OBJECTIVE: To explore the effects of Mg2+ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg2+ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM). DESIGN: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl2 (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450-500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. RESULTS: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg2+in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg2+ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg2+ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg2+ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results. CONCLUSION: Intra-articular injections of Mg2+ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.