An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/ß-Catenin and Erk1/2-MAPK Pathways.

BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. METHODS: MSCs were treated with a gradient concentration of Osthole (6.25 µM, 12.5 µM, and 25 µM). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/ß-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. RESULTS: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/ß-catenin and Erk1/2-MAPK signaling. CONCLUSIONS: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/ß-catenin and Erk1/2-MAPK signaling pathways.

Osthole Inhibits Proliferation and Induces Catabolism in Rat Chondrocytes and Cartilage Tissue.

BACKGROUND/AIMS: Cartilage destruction is thought to be the major mediator of osteoarthritis. Recent studies suggest that inhibition of subchrondral bone loss by anti-osteoporosis (OP) drug can protect cartilige erosion. Osthole, as a promising agent for treating osteoporosis, may show potential in treating osteoarthritis. The purpose of this study was to investigate whether Osthole affects the proliferation and catabolism of rat chondrocytes, and the degeneration of cartilage explants. METHODS: Rat chondrocytes were treated with Osthole (0 µM, 6.25 µM, 12.5 µM, and 25 µM) with or without IL1-ß (10ng/ml) for 24 hours. The expression levels of type II collagen and MMP13 were detected by western Blot. Marker genes for chondrocytes (A-can and Sox9), matrix metalloproteinases (MMPs), aggrecanases (ADAMTS5) and genes implicated in extracellular matrix catabolism were evaluated by qPCR. Cell proliferation was assessed by measuring proliferating cell nuclear antigen (PCNA) expression and fluorescence activated cell sorter. Wnt7b/ß-catenin signaling was also investigated. Cartilage explants from two-week old SD rats were cultured with IL-1ß, Osthole and Osthole plus IL-1ß for four days and glycosaminoglycan (GAG) synthesis was assessed with toluidine blue staining and Safranine O/Fast Green FCF staining, collagen type II expression was detected by immunofuorescence. RESULTS: Osthole reduced expression of chondrocyte markers and increased expression of MMP13, ADAMTS5 and MMP9 in a dose-dependent manner. Catabolic gene expression levels were further improved by Osthole plus IL-1ß. Osthole inhibited chondrocyte proliferation. GAG synthesis and type II collagen were decreased in both the IL-1ß groups and the Osthole groups, and significantly reduced by Osthole plus IL-1ß. CONCLUSIONS: Our data suggested that Osthole increases the catabolism of rat chondrocytes and cartilage explants, this effect might be mediated through inhibiting Wnt7b/ß-catenin pathway.

Molecular mechanisms of the Guizhi decoction on osteoarthritis based on an integrated network pharmacology and RNA sequencing approach with experimental validation.

Background: Our aim was to determine the potential pharmacological mechanisms of the Guizhi decoction (GZD) in the treatment of osteoarthritis (OA) through an integrated approach of network pharmacological analyses, RNA sequencing (RNA-seq), and experimental validation. Methods: The quality control and identification of bioactive compounds of the GZD were carried out by using ultra-performance liquid chromatography (UPLC), and their OA-related genes were identified through overlapping traditional Chinese medicine systems pharmacology database (TCMSP), DrugBank and SEA Search Server databases, and GeneCards. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were implemented after constructing the component-target network. RNA-seq was used to screen differentially expressed genes (DEGs) under intervention conditions with and without the GZD in vitro. The crossover signaling pathways between RNA-seq and network pharmacology were then analyzed. Accordingly, protein-protein interaction (PPI) networks, GO, and KEGG analysis were performed using the Cytoscape, STRING, or DAVID database. The OA rat model was established to further verify the pharmacological effects in vivo. Hematoxylin-eosin (H&E) and safranin O/fast green (S-O) staining were used to grade the histopathological features of the cartilage. We verified the mRNA and protein expressions of the key targets related to the TNF signaling pathways in vivo and in vitro by qPCR, Western blotting (WB), and immunofluorescence assay. In addition, we also detected inflammatory cytokines in the rat serum by Luminex liquid suspension chip, which included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß). Results: Eighteen compounds and 373 targets of the GZD were identified. A total of 2,356 OA-related genes were obtained from the GeneCards database. A total of three hub active ingredients of quercetin, kaempferol, and beta-sitosterol were determined, while 166 target genes associated with OA were finally overlapped. The RNA-seq analysis revealed 1,426 DEGs. In the KEGG intersection between network pharmacology and RNA-seq analysis, the closest screening relevant to GZD treatment was the TNF signaling pathway, of which TNF, IL-6, and IL-1ß were classified as hub genes. In consistent, H&E and S-O staining of the rat model showed that GZD could attenuate cartilage degradation. When compared with the OA group in vivo and in vitro, the mRNA levels of TNF-α, IL-1ß, IL-6, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) were all downregulated in the GZD group (all p < 0.05). The expression levels of anabolic proteins (Col2α1 and SOX9) were all higher in the GZD group than in the OA group (p < 0.05), while the expression levels of the catabolic proteins (MMP9 and COX-2) and TNF-α in the GZD group were significantly lower than those in the OA group (p < 0.05). In addition, the expression levels of TNF, IL-6, and IL-1ß were upregulated in the OA group, while the GZD group prevented such aberrations (p < 0.01). Conclusion: The present study reveals that the mechanism of the GZD against OA may be related to the regulation of the TNF signaling pathway and inhibition of inflammatory response.

[Influence of wind, cold and dampness on clinical manifestation of knee osteoarthritis patients based on the stratifications of traditional Chinese medicine constitution].

OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m-2 with an average of (23.80±2.86) kg·m-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m-2 with an average of(23.42±2.97) kg·m-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m-2 with an average of (24.15±2.33) kg·m-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m-2 with an average of (23.79±2.49) kg·m-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION: The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.

Traditional chinese herbal patch for short-term management of knee osteoarthritis: a randomized, double-blind, placebo-controlled trial.

Objective. To assess the short-term efficacy and safety of two kinds of Traditional Chinese herbal patches, Fufang Nanxing Zhitong Gao (FNZG) and Shangshi Jietong Gao (SJG), for painful knee osteoarthritis (OA). Methods. Patients were randomly enrolled in a double-blind, placebo-controlled study to receive FNZG (n = 60), SJG (n = 60), or placebo patch (n = 30) for 7 days. Outcome measures included visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Questionnaire (TCMSQ) subscale. Results. Although there was no significant difference among, three groups in short-term pain management, patients receiving FNZG got significant improvement in symptom of fear of coldness as compared with placebo patch (P = 0.029). The most common local adverse events of rash, itching, erythema, and slightly damaged skin were observed in 7% of participants. Conclusions. FNZG may be a useful treatment for symptom of knee OA and merits long-term study in broader populations.

Identification of thrombin as a key regulator of chondrocyte catabolic activity through RNA-Seq and experimental verification.

The present study was designed to explore the relationship between thrombin and catabolic activity in chondrocytes. Primary rat chondrocytes were cultured for 24 h with rat serum (RS), rat plasma (RP), or rat plasma supplemented with thrombin (RPT). RNA-sequencing was then performed. Cell proliferation was analyzed by EdU uptake, CCK-8 assays and protein-protein interaction (PPI) network of proliferation-related genes. Heatmaps were used to visualize differences in gene expression. Gene Ontology (GO) enrichment analyses of up- and down-regulated differentially expressed genes were conducted. Molecular probes were used to label the endoplasmic reticulum in chondrocytes from three treatment groups. Immunofluorescence and Safranin O staining were used to assess type II collagen (Col2a1) expression and proteoglycan synthesis, whereas Lox expression was assessed by immunocytochemistry. The expression of enzymes involved in the synthesis and maturation of extracellular matrix (ECM) components and chemokines were measured by qPCR while matrix metalloproteinases (MMPs) levels were evaluated by Western blotting. Relevant nodules were selected through further PPI network analyses. A total of 727 and 1162 genes were up- and down-regulated based on the Venn diagrams comparison among groups. Thrombin was thus able to promote chondrocyte proliferation and a shift towards fibrotic morphology, while upregulating MMPs and chemokines linked to ECM degradation. In addition, thrombin decreased the enzyme expression involved in the synthesis and maturation of ECM.

Self-Reported Weather Sensitivity is Associated with Clinical Symptoms and Structural Abnormalities in Patients with Knee Osteoarthritis: A Cross-Sectional Study.

INTRODUCTION: Patients with knee osteoarthritis (KOA) often complain about clinical symptoms affected by weather-related factors. The purpose of the present study was to use cross-sectional analysis to determine whether weather sensitivity was associated with clinical symptoms, as well as structure abnormalities, in KOA patients. METHODS: Data from 80 participants were obtained from the Feng Hans Shi Effects on OA (FHS) study, an OA cohort study initiated in China in 2015. The weather sensitivity of each participant was determined by a self-reported questionnaire. The following measurements were used to assess clinical outcomes: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for symptoms, and semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS) for cartilage defects and marrow abnormalities of magnetic resonance imaging (MRI). Chi-square with Cochran-Armitage test for trend and regression analysis were used to evaluate the associations between weather sensitivity and WOMAC and WORMS of KOA patients. RESULTS: Most of the KOA participants (57.5%) perceived the weather as affecting their knee-joint clinical symptoms. After adjusting for age, gender, and body mass index (BMI), weather sensitivity was not only associated with knee pain [OR = 3.3 (95% CI 1.1, 9.9), P = 0.032], dysfunction [OR = 5.5 (95% CI 1.8, 16.8), P = 0.003], and overall clinical symptoms [OR = 3.3 (95% CI 1.1, 10.2), P = 0.034], but also associated with cartilage defect [OR = 3.1 (95% CI 1.1, 8.5), P = 0.027] and marrow abnormality [OR = 3.0 (95% CI 1.1, 8.1), P = 0.029]. CONCLUSIONS: In KOA patients, weather sensitivity was associated with clinical symptoms and structural abnormalities. Future longitudinal study is warranted for the causal relationship. INFOGRAPHIC.

Efficacy and safety of external application of Traditional Chinese Medicine for the treatment of acute gouty arthritis: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA). METHODS: Six electronic data bases were retrieved from their inception to march 2017. 15 randomized controlled clinical trials (RCTs) were included. The quality of the literatures was assessed according to Cochrane review criteria by using RevMan5.3 software; and related data was counted using Stata14.0 software. RESULTS: There was no significant difference in C-reactiveprotein (CRP) between experimental intervention group and control group [(WMD = 1.093, 95% CI (－2.514, 4.701); P = 0.553)]. In terms of overall efficacy, the EATCM's treatment group was significantly superior to control group [(OR = 3.692; 95% CI (2.408, 5.661); P < 0.001)]. The EATCM was better than western medicine treatments or other interventions in reducing the adverse reactions [(OR = 0.135; 95% CI (0.067, 0.274); P < 0.001)]. All these funnel plots showed unlikelihood of publishing bias. But due to excessive heterogeneity, the statistical results of serum uric acid and visual analogue scale and CRP between the two groups became uncertain. CONCLUSION: The results indicate that EATCM may have greater overall efficacy with fewer adverse drug reactions, although the evidence is weak owing to the low methodological quality and the small number of the included trials.

[Role of TLR4/NF-κB pathway for early change of synovial membrane in knee osteoarthritis rats].

OBJECTIVE: To study role of TLR4/NF-κB pathway for early change of synovial membrane in knee osteoarthritis rats. METHODS: Eighteen male SD rats weighted (200±20) g were randomly divided into 2 groups, namely control and model group, and 9 in each group. Knee OA model group was established by using modified Hulth method in model group. Control group was not treated. Synovial tissue and serum was extracted at 4 and 21 d after operation. Expression of CD14, TLR4, IL-1ß, TNF-α, ADAMTS-4, MMP-13 were detected by real-time PCR respectively. NF-κB p65 protein was detected by Western-blot; serum concentrations of haluronic acid (HA), N-propeptide of type III procollagen(PIIINP) was detected by Elisa. RESULTS: Expression of CD14, ADAMTS-4, and NF-κB p65 in model group were higher than that of control group at 4 and 21 days after operation, while expression of TLR4, IL-1ß, TNF-α and MMP-13 were higher than that of control group at 21 days after operation(P<0.01). Concentration of PIIINP and HA in model group were higher than that of control group at 4 days after operation, while there was no significant difference at 21 days after operation. CONCLUSIONS: NF-κB pathway could mediate occurrence of KOA by early activating and triggeringg synovial increasingly secreting inflammatory secretion CD14, TLR4, IL-1ß, TNF-α, ADAMTS-4, MMP-13, PIIINP and HA.

Acupotomy for knee osteoarthritis: A systematic review protocol.

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Acupotomy has been widely used to treat KOA. But its efficiency has not been scientifically and methodically evaluated. The aim of this study is to evaluate the efficacy and safety of acupotomy for the treatment of patients with KOA. METHODS: Relevant studies will be searched from the databases of PubMed, EMBASE, Cochrane Library, China Knowledge Resource Integrated Database, Weipu Database for Chinese Technical Periodicals, SinoMed, and Wanfang Database from their inception to June 10, 2019. Two researchers will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. RESULTS: The systematic review will provide high-quality evidence to assess the efficacy and safety of acupotomy for KOA by pain, stiffness, and dysfunction of knee joint, and quality of life, as well as adverse events. CONCLUSION: The systematic review will provide evidence to assess the effectiveness and safety of acupotomy therapy for KOA patients. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019132082.

Bushen Yijing Fang Reduces Fall Risk in Late Postmenopausal Women with Osteopenia: A Randomized Double-blind and Placebo-controlled Trial.

Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, -2.5~-2 SD) were recruited and randomized to orally receive calcium carbonate 300 mg daily with either BSYJF or placebo for 36 months. The effect was further investigated for another 10-year follow-up. During the 36-month administration, there were 12 falls in BSYJF group and 28 falls in placebo group, respectively, indicating 64% lower risk of falls (RR 0.36 [95% CI, 0.18 to 0.71]; P = 0.004) in BSYJF group. During the 10-year follow-up, 36% lower fall risk (RR 0.64 [95% CI, 0.46 to 0.89]; P = 0.009) was observed in BSYJF group. No significant difference was found in safety profile between two groups. Thirty-six-month administration of BSYJF reduced fall risk with an increase in bone mass, and its latent effect on fall risk was continually observed in the 10-year follow-up in late postmenopausal women with osteopenia. This clinical trial was registered at Chinese clinical trial registry (ChiCTR-IOR-16008942).

The MEK-ERK1/2 signaling pathway regulates hyaline cartilage formation and the redifferentiation of dedifferentiated chondrocytes in vitro.

The aim of this study was to investigate the role of the mitogen-activated protein kinase kinase-extracellular signal-regulated kinases 1/2 (MEK-ERK1/2) signaling pathway in chondrocyte differentiation and cartilage tissue construction in vitro. Chondrocytes were stimulated with rat serum (RS) and fetal bovine serum (FBS), and chondrocyte phenotypes were investigated microscopically. Chondrocyte proliferation was analyzed using fluorescence activated cell sorting (FACS) and the CCK8 method. Protein and mRNA expressions were assessed by western blot and RT-qPCR. Constructed cartilage tissues were examined by Safranin O-Fast Green FCF staining and immunofluorescence. In contrast to FBS, RS induced rapid dedifferentiation of chondrocytes and decreased type II collagen expression and proteoglycan synthesis. ERK1/2 and type I collagen expression increased during dedifferentiation and decreased during redifferentiation. Increased MEK-ERK1/2 pathway activity resulted in chondrocyte dedifferentiation, and inhibition of ERK1/2 by the inhibitor PD0325901 reversed dedifferentiation and led to redifferentiation. These data suggest strongly that inhibition of MEK-ERK1/2 activation prevents chondrocyte dedifferentiation and fibrocartilage formation.

The Effectiveness of Manual Therapy for Relieving Pain, Stiffness, and Dysfunction in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Manual therapy is one widely used physical treatment for KOA. OBJECTIVE: To evaluate the effectiveness and adverse events (AEs) of manual therapy compared to other treatments for relieving pain, stiffness, and physical dysfunction in patients with KOA. STUDY DESIGN: A systematic review and meta-analysis of manual therapy for KOA. METHODS: We searched PubMed, EMBASE, the Cochrane Library, and Chinese databases for relevant randomized controlled trials (RCTs) of manual therapy for patients with KOA from the inception to October 2015 without language restrictions. RCTs compared manual therapy to the placebo or other interventional control with an appropriate description of randomization. Two reviewers independently conducted the search results identification, data extraction, and methodological quality assessment. The methodological quality was assessed by PEDro scale. Pooled data was expressed as standard mean difference (SMD), with 95% confident intervals (CIs) in a random effects model. The meta-analysis of manual therapy for KOA on pain, stiffness, and physical function were conducted. RESULTS: Fourteen studies involving 841 KOA participants compared to other treatments were included. The methodological quality of most included RCTs was poor. The mean PEDro scale score was 6.6. The meta-analyses results showed that manual therapy had statistically significant effects on relieving pain (standardized mean difference, SMD = -0.61, 95% CI -0.95 to -0.28, P = 76%), stiffness (SMD = -0.58, 95% CI -0.95 to -0.21, P = 81%), improving physical function (SMD = -0.49, 95% CI -0.76 to -0.22, P = 65%), and total score (SMD = -0.56, 95% CI -0.78 to -0.35, P = 50%). But in the subgroups, manual therapy did not show significant improvements on stiffness and physical function when treatment duration was less than 4 weeks. And the long-term information for manual therapy was insufficient. LIMITATIONS: The limitations of this systematic review include the paucity of literature and inevitable heterogeneity between included studies. CONCLUSION: The preliminary evidence from our study suggests that manual therapy might be effective and safe for improving pain, stiffness, and physical function in KOA patients and could be treated as complementary and alternative options. However, the evidence may be limited by potential bias and poor methodological quality of included studies. High-quality RCTs with long-term follow-up are warranted to confirm our findings.Key words: Knee osteoarthritis, manual therapy, systematic review.

Influence of pain severity on health-related quality of life in Chinese knee osteoarthritis patients.

OBJECTIVE: The aim of this cross-sectional study was to examine the relationship among pain and other symptoms intensity, and health-related quality of life (HRQoL) in Chinese patients with knee osteoarthritis (OA). METHODS: The study was cross-sectional, descriptive, and correlational. A convenience sample of 466 patients with knee OA was recruited in the study. Age, gender, body mass index (BMI), duration of disease, and Kellgren- Lawrence (KL) scores were recorded. HRQoL and symptoms were assessed using the 36-item Short Form Health Survey (SF-36) and the Western Ontario and McMaster (WOMAC) index in participants. RESULTS: The sample was predominantly female (82%) with mean age 56.56 years and mean BMI 24.53 kg/m(2). We found that WOMAC subscale scores significantly negative correlated with the majority of SF-36 subscale scores in knee OA patients (P < 0.05). There were no correlations between BMI, duration of disease, KL score and the vast majority of SF-36 subscale scores in patients (P > 0.05). In addition, there was a significant correlation between age and PCS, gender and MCS in patients (P < 0.05). Regression analysis showed, WOMAC subscale scores significantly negative correlated with the vast majority of SF-36 subscale scores. WOMAC-pain score had the strongest relationship with SF-36 PCS and MCS scores. CONCLUSIONS: In summary, pain severity has a greater impact on HRQoL than patient characteristics, other joint symptoms and radiographic severity in Chinese knee OA patients. Relieving of knee symptoms may help to improve patients' HRQOL. The study provided the evidence that relieving pain should be the first choice of therapy for knee osteoarthritis.

[Case-control study on close reduction combined with minimally invasive percutaneous plate osteosynthesis for the treatment of distal fracture of tibial shaft].

OBJECTIVE: To compare the effects of close reduction combined with minimally invasive percutaneous plate osteosynthesis for distal fracture of tibial shaft. METHODS: From March 2009 to May 2013, there were 124 patients (89 males and 35 females, 30 of them were injured in a traffic accident and 94 were falling down in daily life, the ages ranging from 21 to 81 years old) who suffered from distal fracture of tibial shaft. Sixty-six patients (48 males and 18 females, 45 cases of type A, 12 cases of type B and 9 cases of type C) were treated with close manipulative reduction combined with minimally invasive percutaneous plate fixation. After close reduction, a minimal incision was made and a anatomic plate was inserted just along the medial tibia periostea, and then the fracture was fixed without fracture exposure. The other 58 patients (41 males and 17 females, 41 cases of type A, 10 cases of type B and 7 cases of type C) were treated with conventional open reduction and internal fixation. Length of the incision, operating time, early postoperative pain (recorded using the Visual Analog Scale score) and the outcome results (recorded using the evaluation standard of Johner-Wruhs) were compared. RESULTS: The length of incision was meanly (7.34 ± 1.42) cm in MIPPO group and (21.82 ± 2.35) cm in ORIF group; operation time was (44.48 ± 10.00) min in MIPPO group and (59.42 ± 11.84) min in ORIF group. The postoperative radiographs verified good position of all screws and satisfactory bone fracture reduction in both groups. All the patients were followed up, and the duration ranged from 10 to 24 months (mean 15.2 months) in both groups. In MIPPO group,only one patient had delayed union and got union after Chinese herb therapy. The other 65 patients got bony union during 15 to 20 weeks. While in ORIF group, 3 patients suffered from nonunion and received reoperation with bone grafting, and 4 patients got bone infection. CONCLUSION: Treatment of distal fracture of tibial shaft, combined with close reduction and MIPPO technique, has the advantages such as less invasion, less damage of blood supply, simplified procedure of operation and higher union rate, which is an ideal methods and is accordant to the biological demand.

Effectiveness, medication patterns, and adverse events of traditional chinese herbal patches for osteoarthritis: a systematic review.

Objective. The aim of this study is to systematically evaluate the evidence whether traditional Chinese herbal patches (TCHPs) for osteoarthritis (OA) are effective and safe and analyze their medication patterns. Methods. A systematic literature search was performed using all the possible Medical Subject Headings (MeSH) and keywords from January 1979 to July 2013. Both randomized controlled trials (RCTs) and observational studies were included. Estimated effects were analyzed using mean difference (MD) or relative risk (RR) with 95% confidence intervals (CI) and meta-analysis. Results. 86 kinds of TCHPs were identified. RCTs and controlled clinical trials (CCTs) which were mostly of low quality favored TCHPs for local pain and dysfunction relief. TCHPs, compared with diclofenac ointment, had significant effects on global effectiveness rate (RR = 0.50; 95% CI (0.29, 0.87)). Components of formulae were mainly based on the compounds "Xiao Huo Luo Dan" (Minor collateral-freeing pill) and "Du Huo Ji Sheng Tang" (Angelicae Pubescentis and Loranthi decoction). Ten kinds of adverse events (AEs), mainly consisting of itching and/or local skin rashes, were identified after 3-4 weeks of follow-up. Conclusions. TCHPs have certain evidence in improving global effectiveness rate for OA; however, more rigorous studies are warranted to support their use.

[Regulating effect of anodonta glucan HBP-A on chondrocytes through Wnt pathway].

OBJECTIVE: To investigate regulation function of anodonta glucan HBP-A on chondrocytes through Wnt pathway in vitro. METHODS: Rat chondrocytes were cultured and differentiated induced with IL-1beta (10 ng/ml) in vitro. Chondrocytes were divided into five groups:IL-13 group,IL-1beta + IWP-2 (5 microM,Wnt pathway inhibitor) group, IL-1beta + HBP-A (0.3 mg/ml) group and IL-1beta + IWP-2 + HBP-A group. Wnt-3a, beta-catenin (24 h,48 h,72 h) and MMP-13(72 h) genes expression were detected by Rt-PCR, while beta-catenin, MMP-13, Sox-9 and coll-II (48 h) protein expression were measured by Western-blot. RESULTS: After induction of IL-1beta, gene expression of Wnt-3a, beta-catenin and MMP-13 were increased,so were the protein expression of beta-catenin and MMP-13. In contrast,protein expression of Sox-9 and Coll-II were declined. Following addition of HBP-A, Wnt-3a, beta-catenin and MMP-13 were shown as induction of IL-1beta, but protein expression of Sox-9 and Coll-II were upgraded. Combining HBP-A with IWP-2 led to the lowest level in Wnt-3a, beta-catenin gene and beta-catenin protein expression and highest expression of Sox-9 protein. CONCLUSION: HBP-A could not only delay the differentiation of chondrocytes through downgrading the signal expression of Wnt/beta-catenin,but also adjust the expression of Wnt-3a, beta-catenin and Sox-9 when combinated with the Wnt inhibitor.

[Application of biomarker CTX- II in osteoarthritis].

Effective biomarkers for clinical usage of osteoarthritis are still limited. It was confirmed that C-terminal crosslinking telopeptide of type I collagen (CTX- II) was a specific marker reflecting degradation of articular cartilage. Detection of CTX- II could promptly reflect level of cartilage injury and degradation ,diagnose OA,predict its progress,monitor effects of drug treatment, thus, reflect the condition of osteoarthritis patient indirectly. Application of CTX- II focused mainly on in the early stage of OA and need together to detect with other biomarkers,in order to more accurately reflection of the pathological changes of OA,but the specific clinical significance of CTX- II results still need to improve further.

[Study on the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis].

OBJECTIVE: To explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA). METHODS: From November 2009 to January 2011,70 patients with KOA combined with knee effusion among outpatient and inpatient were analyzed retrospectively. Among the patients, 12 patients were male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were measured respectively by ELISA. The correlation analyses and multiple linear regression analysis were studied to determine associations among biomarkers, clinical variables and radiographic findings of knee joints. RESULTS: The average scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45) respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml respectively. Grouped by less than the lowest quartile and more than the highest quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01; respectively); WOMAC was also positively correlated with K-L score (r=0.692, P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01; r=0.917, P<0.01). It was determined by stepwise regression that the KOA was mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as independent variables (F=20.327, P<0.01). CONCLUSION: WORMS has a better reference value for diagnosis of KOA. The expression of COMP is high in the synovial fluid when WORMS at the high point. The clinical symptoms of knee osteoarthritis are mainly affected by WORMS and K-L score.