Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation.

OBJECTIVE: To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology. METHODS: Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem and Herbal Ingredients' Targets database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these co-targeted genes were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, and protein-protein interaction (PPI) networks were conducted via the search tool for the retrieval of interacting genes (STRING) database. Cell counting kit-8 (CCK-8) assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes (FLS), quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation. RESULTS: Twenty-six co-targeted genes were identified. GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm, and the biological processes mainly involved 'cellular response to hypoxia' 'lipopolysaccharide (LPS)-mediated signaling pathway' and 'positive regulation of gene expression'. KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with 'hypoxia-inducible factor-1 (HIF-1) signaling pathway' and 'tumor-necrosis factor (TNF) signaling pathway'. The PPI network showed that the top 3 hub genes were TP53, TNF, and CASP3. Molecular docking results showed that PF was well docking with TNF. CCK-8 showed no potential toxicity of 10, 20 and 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 ß, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS. CONCLUSION: PF exhibited potent anti-inflammatory effect in OA synovial inflammation.

Advances in Experimental and Clinical Research of the Gouty Arthritis Treatment with Traditional Chinese Medicine.

Gouty arthritis (GA) is a multifactorial disease whose pathogenesis is utterly complex, and the current clinical treatment methods cannot wholly prevent GA development. Western medicine is the primary treatment strategy for gouty arthritis, but it owns an unfavorable prognosis. Therefore, the prevention and treatment of GA are essential. In China, traditional Chinese medicine (TCM) has been adopted for GA prevention and treatment for thousands of years. Gout patients are usually treated with TCM according to their different conditions, and long-term results can be achieved by improving their physical condition. And TCM has been proved to be an effective method to treat gout in modern China. Nevertheless, the pharmacological mechanism of TCM for gout is still unclear, which limits its spread. The theory of prevention and treatment of gout with TCM is more well acknowledged in China than in abroad. In this article, Chinese herbs and ancient formula for gout were summarized first. A total of more than 570 studies published from 2004 to June 2021 in PubMed, Medline, CNKI, VIP, Web of Science databases and Chinese Pharmacopoeia and traditional Chinese books were searched; the current status of TCM in the treatment of GA was summarized from the following aspects: articular chondrocyte apoptosis inhibition, antioxidative stress response, inflammatory cytokine levels regulation, uric acid excretion promotion, immune function regulation, uric acid reduction, and intestinal flora improvement in subjects with gout. The literature review concluded that TCM has a specific curative effect on the prevention and treatment of GA, particularly when combined with modern medical approaches. However, lacking a uniform definition of GA syndrome differentiation and the support of evidence-based medicine in clinical practice have provoked considerable concern in previous studies, which needs to be addressed in future research.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine in Treating Gouty Arthritis: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Gouty arthritis is a common metabolic disease caused by long-term purine metabolism and elevated serum uric acid. In recent years, the incidence of gouty arthritis has been increasing year by year. As an effective method for treating gouty arthritis, acupuncture combined with herbal medicine has been widely used in clinical practice. However, the evidence for the treatment needs to be evaluated through systematic review and meta-analysis. Methods. The Cochrane Library, PubMed, Web of Science, EMBASE, China CBM database, Clinical Trials, CNKI, China Wanfang database, and VIP information database were searched from the establishment of each database to March 2021. Randomized controlled trials (RCTs) were included in the study, and the therapeutic effects of acupuncture combined with herbal medicine versus conventional therapy, or acupuncture combined with herbal medicine versus anti-inflammatory drugs, or acupuncture combined with herbal medicine versus acupuncture/herbal medicine alone were compared in the subjects with gouty arthritis. Two authors screened all references, assessed the risk of bias, and independently extracted the data. The binary outcome was summarized using 95% confidence intervals (CIs) and risk ratios (RRs). The overall quality of the evidence was assessed with hierarchy, and meta-analysis was performed with a random-effects model. RESULTS: A total of 14 randomized controlled trials (1,065 participants, 540 treatment groups, and 525 control groups) with treatment courses of 5 to 21 days were included. Acupuncture combined with herbal medicine and acupuncture was compared in three trials, acupuncture combined with herbal medicine and conventional therapy was compared in 14 of them, and acupuncture combined with herbal medicine and anti-inflammatory drugs was compared in 8 of them. The clinical efficacy (clinical symptoms, serological tests, and visual analogue scale (VAS) results) was significantly improved in the acupuncture combined with herbal medicine treatment group (P=0.0005, 95% CI 0.03 to 0.13; 687 participants; 8 trials), and the efficacy in reducing uric acid was also better (P < 0.00001; 95% CI -102.89, -68.37; 100 participants; 2 trials; evidence with moderate quality). The effect of acupuncture combined with herbal medicine was better than that of acupuncture alone (RR 1.22, 95%CI 1.06 to 1.41; 139 participants; 3 trials), the effect of acupuncture combined with herbal medicine was better than that of herbal medicine alone (RR 1.31 95%CI 1.08 to 1.57, 100 participants, 2 trials, evidence with moderate quality), and the effect of acupuncture combined with herbal medicine was better than that of colchicine (P = 0.02, RR 1.14 95%CI 1.02 to 1.27, 2 trials, evidence with moderate quality). The incidence of adverse events was considerably different between the two groups, and the acupuncture combined with herbal medicine group was significantly superior to the control group in terms of adverse events (P < 0.00001; 95% CI (0.08 to 0.32)). CONCLUSIONS: The efficacy of acupuncture combined with herbal medicine was better than conventional drug therapy in treating gouty arthritis. The study results must be interpreted with caution due to the high or unclear risk of bias of the trials included in the study. PROSPERO registration number: CRD42020202544. INPLASY registration number: 202090006.

Gua sha therapy for chronic low back pain: A protocol for systematic review.

BACKGROUND: Non-specific chronic low back pain (LBP) is a debilitating disease that profoundly impacts patients' daily physical function and quality of life. Gua sha therapy, as an easy-to-use and noninvasive complementary modality, has been widely used clinically in patients with non-specific chronic LBP. The aim of this study is to test the potential benefits and harms of gua sha therapy on patients with non-specific chronic LBP. METHODS: Ten English databases, 3 Korean databases, 6 Chinese databases, 1 Japanese database, and 2 Brazilian databases will be searched from their inception to September 2019. Randomized controlled trials will be included if gua sha therapy was used as the sole treatment or as a part of combination therapy with other treatments in patients with non-specific chronic LBP. Two reviewers will independently extract the data and assess the methodological quality using the Cochrane criteria for risk of bias. The meta-analysis will be performed using Review Manager 5.3 software. RESULTS: The findings of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will provide more evidence regarding the clinical usage of gua sha therapy for non-specific chronic LBP. TRIAL REGISTRATION NUMBER: CRD42019134567.

[Effect of Tongluo Zhitong (, TLZT) gel preparation on p53 /miR-502-5p /NF-κBp65 in synovial tissue of knee osteoarthritis].

OBJECTIVE: To observe effects of Tongluo Zhitong (, TLZT) gel preparation on p53, miR-502-5p, NF-κBp65 in synovial tissue of knee osteoarthritis (KOA), and to explore mechanism of TLZT gel preparation in treating KOA. METHODS: Thirthy-six Wistar rats aged 8 weeks and weighed 200 to 220 g (meaned 208 g) were randomly divided into normal group, model group and traditional Chinese medicine (TCM) group, 12 rats in each group. KOA model was established by modified Hulth method. After 4 weeks of modeling, TCM group treated with TLZT gel preparation for external use, 3 times daily for 2 weeks;normal group and model group were fed normally without intervention. After treatment, morphological changes of specimens in each group were observed, changes of miR-502-5p in synovial tissue were detected by qPCR, and contents of p53, NF-κBp65, IL-1ß, TNF-α, MMP-13 in synovial tissue were detected by qPCR and Western Blot respectively. RESULTS: (1)Morphological observation of specimens showed that the articular cartilage in model group was hyaline and uneven, the synovial membranes were hypertrophic and proliferative with a large number of inflammatory cells infiltrating, the joint fluid was thicker in texture;the articular cartilage in TCM group was more transparent and smooth, synovial hyperplasia was mild with a small amount of inflammatory cell infiltration, the texture of articular fluid was clear and sparse. (2) Compared with normal group, content of miR-502-5p of synovial tissue in model and TCM group were increased, mRNA and expression of p53 decreased, expression of NF-κBp65, IL-1ß, TNF-α, MMP-13 increased. (3)Compared with model group, content of miR-502-5p in synovial tissue of TCM group decreased (P<0.05), mRNA and protein expression of p53 increased (P<0.05), mRNA and protein expression of NF-κBp65, IL-1ß, TNF-α, MMP-13 decreased (P<0.05). CONCLUSION: Expression of p53, miR-502 -5p, NF -κBp65 in synovial tissue is closely related to synovial hyperplasia and inflammatory reaction, TLZT gel preparation may reduce proliferation and inflammatory reaction of KOA synovium by regulating the expression of p53, miR- 502-5p, NF-κBp65 in synovial tissues.

[Lapidus operation combined with bone setting manipulation in treatment of hallux valgus in elderly patients].

OBJECTIVE: To investigate the clinical effect of Lapidus operation combined with bone setting manipulation of traditional Chinese medicine in treating hallux valgus in elderly patients. METHODS: From March 2013 to October 2017, 53 elderly patients (87 feet) with hallux valgus were treated with Lapidus operation combined with bone-setting manipulation of traditional Chinese medicine, including 12 males (18 feet) and 41 females (69 feet), ranging in age from 65 to 92 years old, with an average of (76.3±4.8) years old. Visual analogue scale(VAS) was used to evaluate the degree of relief of foot pain before and 26 months after operation. American Orthopaedic Foot and Ankle Society(AOFAS) was used to evaluate the function of foot pain. The changes of hallux valgus angle(HVA angle), interphalangeal angle (IMA angle) and metatarsal wedge angle(MCA angle) were compared on X-ray films. RESULTS: All the patients were followed up, and the duration ranged from 12 to 42 months, with an average of(26.0±2.7) months. In all patients, the first metatarsal joint reached bone fusion within 6 to 8 months, with an average of 4.7 months. The preoperative VAS score was 8.06±1.44, which was significantly different from 2.14±1.98 at 26 months(P<0.05). The preoperative AOFAS score was 53.90±7.89, which was significantly different from 92.80±2.78 at 26 months(P<0.05). The HVA, IMA and MCA were significantly improved from preoperative(38.60±2.72)°, (21.90±1.91)° and(20.90±2.20)° to the latest follow-up(17.80±1.94)°, (9.70±2.56)° and(11.70±0.48)°(P<0.05). According AOFAS score, 74 feet got an excellent result, 11 good and 2 fair. CONCLUSIONS: Lapidus operation combined with bone-setting manipulation of traditional Chinese medicine on the treatment of hallux valgus foot in elderly patients has satisfactory clinical effects, shortens the time of osteotomy and fixation, protects the soft tissue around the osteotomy end and promotes the bone fusion on the most satisfactory position.