Electroacupuncture Delays Cartilage Degeneration by Modulating Nuclear Factor-κB Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA).@*METHODS@#Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis.@*RESULTS@#EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01).@*CONCLUSION@#EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.

Tackling Osteoarthritic Knee Pain with Electroacupuncture / 中国结合医学杂志

Electroacupuncture (EA) has been widely used in pain relief. Clinical evidence has revealed its unique advantages and effectiveness in alleviating pain. Studies on EA and pain relief have revealed that EA displays greater analgesic effects for different types of pain in comparison to manual acupuncture. Here, we reviewed the clinical application and mechanism of EA in treating osteoarthritic knee pain and its influence factors in curative effect.

Perspective on the Development of Integrative Medicine Based on the Paradigm Theory: On the Connotation and Extension of Integrative Medicine / 中国中西医结合杂志

Integrative medicine (IM) has made great progress after more than half a century practice. However, many issues are yet to be in-depth explored. How to define clinical connotation and extension of IM, how to define feasible methods and means for diagnosis and treatment of IM, how to train more skilled talents of IM, how to elevate clinical efficacy of IM, these are all topics in need of further study. In this paper authors explored the clinical development mode of IM, extracted connotation and extension of IM clinics, hoping to promote the development of IM clinics.

Diagnosis and management of knee osteoarthritis: Chinese medicine expert consensus (2015) / 中国结合医学杂志

Literature review shows that Chinese medicine and other related treatment are still the main stream treatment of knee osteoarthritis. Currently, there is short of handbook guiding Chinese medicine from evidence-based medical evidence, so it is a top priority to develop a clinical guideline from the expert consensus. After several rounds of discussion during the conference and examination by letter, which has collected opinions from nearly one hundred experts, consensus was reached. Nonpharmacologic interventions include health education, medical exercise, acupuncture, massage, acupotomology, and physiotherapy. Pharmacological interventions are as follows. Topical application includes fumigation, application, hot compressed, ironing and iontophoresis with Chinese herbs, etc. Chinese patent medicine for external use includes plaster, ointment, etc. Western medicine for external use mainly includes emulsion, ointment, plaster and embrocation containing nonsteroidal anti-inflammatory drugs (NSAIDs). Intraarticular injection mainly includes sodium hyaluronic acid, chitosan (for injection) with prudent use of glucocorticoid. Chinese herbal medicine and Chinese patent medicine can be taken referring to syndrome differentiation which mainly includes syndromes of qi stagnation and blood stasis, cold dampness, deficiency of Gan (Liver) and Shen (Kidney), deficiency of qi and blood. Western medicine mainly includes analgesic, NSAIDs, diseases modifying drugs. Surgery procedures mainly include joint irrigation, arthroscopic surgery, osteotomy, arthroplasty, etc.

Comparative research on computer simulation of two different therapeutic principles and formulae for osteoarthritis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To compare the effect of reinforcing Shen method (RSM) and activating blood method (ABM) in treating osteoarthritis (OA) at the molecular level.</p><p><b>METHODS</b>The physical and chemical characteristics of components from respective recipes of RSM and ABM, and network features of component-target interaction network were analyzed by computer simulation methods including chemical space, molecular docking, and biological network, etc.</p><p><b>RESULTS</b>The chemical components of RSM and ABM were scarcely scattered with larger overlapping. Among established networks, the distribution of network features was partially similar in RSM and ABM. The average target number correlated with each component was 1.86 in RSM and 2.11 in ABM respectively. Each average target number was respectively correlated with 4.46 compounds and 3.93 compounds, reflecting multi-component and multi-target actions.</p><p><b>CONCLUSION</b>Computer simulation could intuitively trace out similarities and differences of two different methods and their interaction with targets, which revealed that the compatibility of RSM and ABM could have broader protein targets and potential synergism at the molecular level.</p>

Effect of water extracts from duhuo jisheng decoction on expression of chondrocyte G1 phase regulator mRNA / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of water extracts from Duhuo Jisheng decoction on chondrocyte G1 phase.</p><p><b>METHODS</b>Chondrocytes were collected from four-week-old SD rats to establish the chondrocyte in vitro culture system. The third generation of chondrocytes was intervened. MTT method was used to measure the effect of water extracts from different concentrations of Duhuo Jisheng decoction on chondrocyte activity. The expressions of Chondrocyte Cyclin D1, CDK4, CDK6 and P21 mRNA in the blank group and low, middle and high-dose groups (100, 200, 400 mg x L(-1)) were detected by RT-PCR method.</p><p><b>RESULT</b>The MTT assay showed that the chondrocyte activity significantly increased within specific drug concentrations (50-800 mg x L(-1)) (P < 0.01); After the intervention for 24 h, the expressions of CyclinD1, CDK4 and CDK6 mRNA in all dose groups notably increased (P < 0.05), with the maximum expressions at the concentration of 200 mg x L(-1); The expression of P21 mRNA decreased, particularly at the concentration of 200 mg x L(-1) (P < 0.01).</p><p><b>CONCLUSION</b>Water extracts from Duhuo Jisheng decoction can promote chondrocyte proliferation by effecting the expression of chondrocyte G1 phase regulator mRNA.</p>

Pien Tze Huang induced apoptosis in human colon cancer HT-29 cells is associated with regulation of the Bcl-2 family and activation of caspase 3 / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the cellular effects of Pien Tze Huang (PZH) in the HT-29 human colon carcinoma cell line.</p><p><b>METHODS</b>The viability of HT-29 cells was determined by MTT assay. A fluorescence-activated cell sorting (FACS) analysis with annexin-V/propidium iodide (PI) and JC-1 staining were performed to determine cell apoptosis and the loss of mitochondrial membrane potential, respectively. Activation of caspase 3 was evaluated by a colorimetric assay. The mRNA expression levels of Bcl-2 and Bax were measured by reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>PZH, in a dose- and time-dependent manner, reduced viability and induced apoptosis of HT-29 cells. Moreover, PZH treatment resulted in the collapse of the mitochondrial membrane potential, activation of caspase 3, and an increase in the Bax/Bcl-2 ratio.</p><p><b>CONCLUSION</b>PZH inhibits the growth of HT-29 cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and activation of caspase 3, which may, in part, explain its anticancer activity.</p>

Potential synergistic and multitarget effect of herbal pair Chuanxiong Rhizome-Paeonia Albifora Pall on osteoarthritis disease: a computational pharmacology approach / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the polypharmacological mechanism of herbal pair Chuanxiong Rhizome-Paeonia Albifora Pall (HP CXR-PAP) on the treatment for osteoarthritis (OA).</p><p><b>METHODS</b>Chemical space was used to discuss the similarities and differences between the molecule sets of HP CXR-PAP and drugs. Docking protocol was used to study the interaction between HP CXR-PAP and OA target enzymes. The similarities and differences of HP CXR-PAP and drugs in target spaces were elucidated by network features.</p><p><b>RESULTS</b>The plots between the molecule sets of HP CXR-PAP and drugs in chemical space had the majority in the same region, and compounds from HP CXR-PAP covered a much larger additional region of space than drug molecules, which denoted the diverse structural properties in the molecule set of HP CXR-PAP. The molecules in HP CXR-PAP had the properties of promiscuous drugs and combination drug, and both HP CXR-PAP ligand-target interaction network and drug ligand-target interaction network were similar in the interaction profiles and network features, which revealed the effects of multicomponent and multitarget.</p><p><b>CONCLUSION</b>The clue of potential synergism was obtained in curing OA disease by Chinese medicine, which revealed the advantages of Chinese medicine for targeting osteoarthritis disease.</p>

Experimental study on the suppression of sodium nitroprussiate-induced chondrocyte apoptosis by Tougu Xiaotong Capsule (透骨消痛胶囊)-containing serum / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the mechanism of action of Tougu Xiaotong Capsule (透骨消痛胶囊, TGXTC) ex vivo in suppressing chondrocyte (CD) apoptosis induced by sodium nitroprussiate (SNP).</p><p><b>METHODS</b>Thirty New Zealand rabbits, 2 months old, were randomized by lottery into five groups, six in each: the blank group treated with saline, the positive control group treated with Zhuanggu Guanjie Pill (壮骨关节丸, 70 mg/kg), and the three experimental groups, EGA, EGB, and EGC, treated with low dose (35 mg/kg), moderate dose (70 mg/kg), and high dose (140 mg/kg) of TGXTC, respectively. All treatments were administered via gastrogavage twice a day for 3 days. Arterial blood was collected from the abdominal aorta and drug or drug metabolites-containing serum was prepared. CDs obtained from knee joints of 16 four-week-old New Zealand rabbits were cultured to the third passage and confirmed by toluidine blue staining. SNP of various final concentrations (0, 0.5, 1.0, and 2.0 mmol/L) was used to induce CD apoptosis, and the dosage-effect relationship of SNP in inducing CD apoptosis was determined. Serum samples from the blank, control, and three dosages of TGXTC-treated rabbits were tested in the CD culture in the presence of SNP. Cell apoptosis was determined by Hoechst 33342 staining, viability of CDs was quantified by MTT, CD apoptosis rate was determined by annexin V-FITC/PI staining, levels of p53 and Bcl-2 mRNA expression in CDs were determined with RT-PCR, and contents of caspase-3 and caspase-9 proteins were determined by colorimetry.</p><p><b>RESULTS</b>CD apoptosis was induced by SNP at all concentrations tested and in a dose-dependent manner. The SNP concentration of 1 mmol/L and treatment duration of 24 h appeared to be optimal and were selected for the study. Serum samples from the positive control rabbits and from the two higher doses of TGXTC-treated rabbits showed reduction of SNP-induced CD apoptosis, decrease in p53 mRNA expression, inhibition of catalytic activities of caspase-3 and caspase-9, and increase in Bcl-2 mRNA expression when compared with the serum from the blank group (P<0.05).</p><p><b>CONCLUSION</b>TGXTC-containing sera antagonized SNP-induced CD apoptosis and the molecular basis for the action was associated with up-regulation of Bcl-2, down-regulation of p53 expression, and inhibition of caspase-3 and caspase-9 catalytic activities.</p>

Clinical study on the treatment of knee osteoarthritis of Shen-Sui insufficiency syndrome type by electroacupuncture / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the clinical effificacy of electroacupuncture (EA) on treating knee osteoarthritis (KOA) of Shen ()-Sui () insuffificiency (SSI) syndrome type.</p><p><b>METHODS</b>A total of 245 patients (279 knees) of KOA-SSI were randomly assigned to two groups by lottery: 141 knees in the treatment group and 138 knees in the control group. The treatment group was managed with EA at the dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with 15 days as one course; 2 courses were applied with a 5-day interval in between. The control group was treated with intra-articular injection of 2 mL hyaluronic acid into the affected joint every 7 days for 5 times in total. The clinical effects on the patients in different stages were observed, and their symptom scores of knee and contents of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2alpha) (PGE(2alpha)) and matrix metalloproteinases-3 (MMP-3), in the knee joint fluid were measured before and after treatment.</p><p><b>RESULTS</b>The study was completed in 235 patients (263 knees); four patients (7 knees) in the treatment group and six patients (9 knees) in the control group dropped out. Comparison of therapeutic effects (excellent and effective rates) between the two groups showed insignificant differences (P>0.05). Symptom scores of knee and contents of cytokines in the knee flfluid after treatment were lowered signifificantly in the patients of stage I-III in both groups (P<0.05 or P<0.01). However, the lowering of the total symptom score of knee in the patients of stage III in the treatment group was more signifificant (P<0.05).</p><p><b>CONCLUSIONS</b>EA could effectively alleviate the clinical symptoms in KOA patients of stage III, showing an effect superior to that of hyaluronic acid. EA also shows action in suppressing the secretion of IL-1, IL-6, TNF-alpha, PGE(2alpha) and MMP-3 in the knee flfluid.</p>

Computational pharmacology study of tougu xiaotong granule in preventing and treating knee osteoarthritis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the pharmacological properties of Tougu Xiaotong Granule (TGXTG) in preventing and treating knee osteoarthritis (KOA) at the molecular level.</p><p><b>METHODS</b>The computational methods, including principal component analysis, molecular docking, target-ligand space distribution, and the predictions of absorption, distribution, metabolism, excretion and toxicity (ADMET), were introduced to characterize the molecules in TGXTG.</p><p><b>RESULTS</b>The structural properties of molecules in TGXTG were more: diverse than those of the drug/drug-like molecules, and TGXTG could interact with significant target enzymes related to KOA. In addition, the cluster of effective components was preliminarily identified by the target-ligand space distributions. As to the results of ADMET properties, some of them were unsatisfactory, and were merely regarded as references here.</p><p><b>CONCLUSION</b>Based on this computational pharmacology study, TGXTG is a broad-spectrum recipe inhibiting many important target enzymes, which could effectively postpone the degeneration of spectrum cartilage by coordinately inhibiting the biological effects of cytokines, matrix metallopeptidase 3, and oxygen free radicals. radicals.</p>

Effect of OA kneepad on apoptosis genes Bcl-2 and p53 expression in articular cartilage cells of experimental knee osteoarthritis / 中国骨伤

<p><b>OBJECTIVE</b>To study the effects of kneepad on expression of Bcl-2 and p53 mRNA of chondrocyte in white rabbits with knee osteoarthritis, so as to explore and treatment mechanism of OA kneepad on apoptosis of chondrocytes of rabbits with knee osteoarthritis in molecular degree.</p><p><b>METHODS</b>Forty-four Japanese healthy 6-month-old rabbits (equal male and female,the weight ranging from 2 to 2.2 kg) were used to establish knee osteoarthritis models by modified Hulth method. The rabbits were randomly divided into 6 groups: normal group, model group, control group (microwave), experimental group 1 (electricity), experimental group 2 (thermal), experimental group 3 (kneepad). Ten rabbits in the normal group were breed with conventional method; 9 rabbits in the model group were breed with conventional method after model made; 9 rabbits in the control group were treated with microwave for 30 minutes, one time daily; 9 rabbits in the experimental group 1 were treated with electricity (density wave) for 30 minutes,one time daily;8 rabbits in the experimental group 2 were treated with hot (hot soft membrane) for 30 minutes, one time daily; 9 rabbits in the experiment group 3 were treated with electrothermal (OA knee pad) for 30 minutes, one time daily. All the rabbits were treated for 16 weeks and then sacrificed. The expressions of Bcl-2 and p53 mRNA of chondrocytes in knee joint were detected by using fluorescence quantitative RT-PCR method.</p><p><b>RESULTS</b>At the 16 hthek,th e OD260/OD280 value range of total RNA extracted from rabbit articular cartilage tissue in each group were all at 1.80 to 2.00,wh ich indicates high RNA purity. The p53 relative mRNA in articular cartilage cells of model group,th e control group,th e experimental group 1 ,r oup 2,gr oup 3 were overexpressed,an d Belc2 mRNA expression levels of articular cartilage cells were low expression,an d compared with the normal group there were significant differences (P < 0.01). Belc2, p53 mRNA expression in articular cartilage cells,th ere were significant differences (P < 0.01) between the control group, experimental group 1, group 2, group 3 and model group. The results between the control group, experimental group 1 ,group 2 and group 3 had significant differences (P < 0.01).</p><p><b>CONCLUSION</b>OA-kneepad can up-regulate the mRNA expression of Bcl-2 as well as down-regulate the mRNA expression of p53, thereby to inhibit the apoptosis of cartilage cells and delay the degeneration of articular cartilage changes.</p>

Research on mechanism of Tougu Xiaotong Granule in preventing and treating knee osteoarthritis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of Tougu Xiaotong Granula (TXG) on prevention and treatment of knee osteoarthritis.</p><p><b>METHODS</b>Fifty New Zealand rabbits were randomly divided into 6 groups. Except those in the normal control group, all the rabbits were replicated into knee osteoarthritis model using modified Hulth method. They were administered by gastrogavage once every day respectively with 100 ml of normal saline to the rabbits in the normal group and those in the model group, with 10 g of Zhuanggu Guanjie Pill to those in the control group, and 5 g, 10 g and 20 g of TXG to those in the three TXG tested groups (tested group 1, 2 and 3). The levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and metalloproteinase 3 (MMP-3) in joint fluid, the blood content of malondialdehyde (MDA) and nitric oxide (NO) absorbance as well as the SOD activity in synovia were observed.</p><p><b>RESULTS</b>Overexpressions of IL-1, IL-6, TNF-alpha and MMP-3 in joint fluid, increased blood content of NO and MDA were shown in the 8th and 16th week, and decreased SOD activity in synovia was shown in the 16th week of the experiment in all the model rabbits, as compared to those in the normal group, the difference was significant respectively (P < 0.05 or P<0.01). After 8 weeks of treatment, the levels of IL-1, TNF-alpha, MMP-3, NO and MDA in the control group, tested group 2 and 3 were significantly different to those in the model group respectively (P < 0.05, P < 0.01), and significant difference was also shown in the comparisons of those indexes between the control group and the tested group 1 vs the tested group 3 (P < 0.05). As for the level of IL-6, significant difference was shown in comparisons of the model group with the control group, tested group 2 and 3 in the 8th and 16th week of the treatment (P < 0.05 or P < 0.01), also in comparison of the tested group 3 with the tested group 1 in the 8th week, and in that of the tested group 2 with the control group and the tested group 1 in the 16th week (P < 0.05).</p><p><b>CONCLUSION</b>TXG could effectively postpone the degeneration of cartilage through effectively inhibiting the biological effects of cytokines, MMP-3 and oxygen free radical.</p>

Experimental study on replicating knee osteoarthritis by modified Hulth's modeling method / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the method of replicating experimental animal model of knee osteoarthritis.</p><p><b>METHODS</b>Knee osteoarthritis was replicated by modified Hulth's modeling method. X-ray photographic and transmission electron microscopic examination, test of the joint synovial fluid of the modeled joint were performed, and serum contents of malondialdehyde (MDA) and nitric oxide (NO) in blood were measured.</p><p><b>RESULTS</b>(1) In the normal control group, the articular surface is smooth and glossy, with intact cells and cellular membrane. In the model group, the medial space of the knee joint became obvious narrowed with rough and deformed articular surface and osteophytes, as well as the atrophic chondrocytes with pyknotic cell nucleus and broken cellular membrane. (2) Eight weeks and 16 weeks after modeling, in the model group, the contents of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-3 (MMP-3) in synovial fluid and the levels of serum MDA and NO were obviously raised, and the activity of superoxide dismutase (SOD) in synovial membrane was obviously lowered 16 weeks after modeling, showing significant difference when compared with those in the normal control group (P < 0.01).</p><p><b>CONCLUSION</b>Modified Hulth's modeling method in replicating knee osteoarthritis is simple in manipulation with less wound, and the condition of modeled knee joint could be maintained stable to certain degree, which is advantageous to the success of animal model replicating.</p>