[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.

Associations between weather conditions and osteoarthritis pain: a systematic review and meta-analysis.

BACKGROUND: Although there is an assertion that weather conditions affect osteoarthritis (OA) pain, the results from clinical studies remain inconsistent. This meta-analysis was performed to evaluate the association between weather conditions and OA pain. METHODS: Cochrane Library, Embase, PubMed, and Web of Science were searched from inception to September 30, 2022. Observational studies that explored all weather conditions associated with pain intensity were included. In the systematic review, the methodological quality of the selected studies was assessed and a best-evidence synthesis was used to make qualitative conclusions. Based on homogeneous results, Fisher's Z scores derived from the effect size of temperature (T), barometric pressure (BP) or relative humidity (RH) related to OA pain were synthesized and further transformed to the correlation coefficients (summary r) in meta-analysis. RESULTS: A total of 14 studies were included in the best-evidence synthesis of a qualitative systematic review. There was strong evidence with 13 of 14 studies reporting consistent findings that weather factors in general, including any kind of meteorological condition, were associated with OA pain. Subsequently, 3 studies regarding BP or T, and 5 studies regarding RH with the pain of OA were included in quantitative meta-analyses. Both BP (pooled Fisher's Z = 0.37, 95% CI 0.15 to 0.59; summary r = 0.35, 95% CI 0.15 to 0.53) and RH (pooled Fisher's Z = 0.10, 95% CI 0.01 to 0.18; summary r = 0.086, 95% CI -0.05 to 0.22) were positively related to OA pain, while T was negatively related to OA pain (pooled Fisher's Z = -0.38, 95% CI -0.60 to -0.16; summary r = -0.36, 95% CI -0.54 to -0.16). CONCLUSIONS: In this study, weather factors in general were significantly associated with OA pain. It may provide useful references for the daily health management of OA. More studies designed with the consistent meteorological condition are warranted to validate the findings.KEY MESSAGEMany people with osteoarthritis think their joint pain is affected by the weather, while the association between OA pain and weather conditions is still unclear.This is a systematic review and meta-analysis of 14 observational studies for the association between weather conditions and OA pain.Weather conditions appear to be associated with OA pain. Barometric pressure and relative humidity were positively correlated to OA pain intensity, while temperature was negatively correlated to OA pain.

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.

The Effect of Manipulation Under Anesthesia for Secondary Frozen Shoulder: A Randomized Controlled Trial.

INTRODUCTION: Manipulation under anesthesia (MUA) is often used for frozen shoulder treatment, but controversy still exists regarding MUA compared with conservative treatment. This research was conducted to compare the outcome between MUA and celecoxib (CLX) in secondary frozen shoulder. METHODS: Patients with secondary frozen shoulder were randomized into two groups, an MUA plus exercise (EX) group and a CLX plus EX group. Clinical outcomes were documented at baseline and at 1 day, 2, 4, and 12 weeks after intervention, including Constant-Murley Score (CMS) for function, Pain Rating Index (PRI) and Present Pain Intensity (PPI) for pain, passive range of motion (ROM) measurements including external rotation, internal rotation, forward flexion, and abduction. Primary outcome was CMS. Secondary outcomes were PRI, PPI, and passive ROM. RESULTS: Sixty-seven patients out of 68 in the MUA group and 66 out of 68 in the CLX group finished the entire study period. There were no significant differences in basic properties of the two groups before intervention. As the primary outcome, CMS changes in the MUA group improved faster than the CLX group. Secondary outcomes, passive ROM, and pain PPI were faster and significant in the MUA group from 1 day after intervention compared with CLX (P < 0.05). At 12 weeks, a statistically significant difference was not observed in the PPI (P > 0.05). A statistically significant difference was not observed in the PRI between groups in 1 day (P > 0.05). For the primary outcome, from 0 to 12 weeks the mean changes in CMS were 44.00 for MUA plus EX (95% CI 43.07-44.93, P < 0.001) and 27.09 for CLX plus EX (26.20-27.98, P < 0.001). The significant difference in improvement appeared from 2 weeks. CONCLUSION: To treat secondary frozen shoulder with MUA, this treatment could achieve better therapeutic effects on improvement of function, pain, and passive ROM than CLX did. CLINICAL TRIAL REGISTRATION: The trial was registered at www.chictr.org.cn , identifier ChiCTR2200060269.

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.

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.

[Effect of acupuncture therapy on patients with low back pain: a Meta-analysis].

OBJECTIVE: To systematically review the clinical efficacy of acupuncture on the patients with low back pain (LBP). METHODS: Randomized controlled trials (RCTs) about pure acupuncture therapy versus other treatments in treating LBP were electronically searched in PubMed, CBM, EMbase, The Cochrane Library, CNKI, VIP and Wanfang Data from January 2004 to May 2014. The observed index on the results were the changed scores of VAS, ODI, JOA and RMDQ. Two reviewers independently screened the literatures according to the inclusion and exclusion criteria, as well as the extracted data, and assessed the methodological quality. The results of Meta-analysis was conducted by RevMan 5.2 software. RESULTS: Ten RCTs involved 751 patients were finally included. The results of Meta-analysis indicated that the role of pure acupuncture group in improving the VAS score was better than that of the control group, and the combined effect size was RR = -.32, 95% CI (-1.41, -1.22); Z=27.28, P<0.00001; the role of pure acupuncture group in improving the ODI score was better than that of the control group, and the combined effect size was RR = -5.07, 95% CI (-7.50, -2.65); Z=4.10, P<0.0001; the role of pure acupuncture group on improved JOA score was better than that of the control group and the combined effect size was RR=2.83, 95% CI (2.02, 3.63), Z=6.90, P<0.00001. The role of pure acupuncture group in improving the RMDQ score was better than that of the control group, and the combined effect size was RR = -2.80, 95% CI (-3.49, -2.11), Z=7.95, P<0.00001. CONCLUSION: The result of meta-analysis demonstrates that pure acupuncture may have a favorable effect on self-reported pain and functional limitations in LBP patients.

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.

[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.