Investigation of pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm based on a "disease-syndrome-symptom-formula" association network analysis / 药学学报

Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.

Establishment and evaluation of rabbit model of closed tibial fracture / 中国骨伤

OBJECTIVE@#To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture.@*METHODS@#The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation.@*RESULTS@#Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing.@*CONCLUSION@#The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.

Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid / 中国中药杂志

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

Effect of Panlongqi Tablet on Cervical Spondylosis of Vertebral Artery Type in Rats / 中国实验方剂学杂志

Objective:To establish a model of cervical spondylosis of vertebral artery type （CSA） in rats by mixed modeling method， and observe the intervention effect of Panlongqi tablet （PLQT） on CSA rats. Method:SD rats were divided into a normal control group， a model group， low- （0.16 g·kg^-1）， medium- （0.32 g·kg^-1）， and high-dose （0.64 g·kg^-1） PLQT groups， and a Jingfukang granule （JFK， 1.35 g·kg^-1） group. The rats were treated correspondingly 24 hours after modeling for eight weeks， and those in the normal control group received an equal volume of normal saline by gavage. The limb movement was tested by the inclined plate assay， vertebral artery flow volume by multi-mode high-frequency sound wave for small animals， and microcirculatory blood flow in the pia mater by the laser Doppler. The imaging of the cervical spine was recorded and scored by X-ray micro-computed tomography （Micro CT）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of endothelin-1 （ET-1）， nitric oxide （NO）， tissue plasminogen activator （t-PA）， and plasminogen activator inhibitor （PAI）. Result:Compared with the normal control group， the model group showed decreased limb movement， vertebral artery flow volume， and microcirculatory blood flow in the pia mater， and increased imaging of the cervical spine and score （<italic>P</italic><0.05，<italic>P</italic><0.01）. PLQT could dose-dependently improve the motor function， increase the vertebral artery flow volume and microcirculatory blood flow in the pia mater， and reduce the degree and score of imaging of the cervical spine in CSA rats（<italic>P</italic><0.05，<italic>P</italic><0.01）. The serum levels of NO and t-PA were decreased and those of ET-1 and PAI were increased in the model group as compared with those in the normal control group， while such changes were reversed by PLQT treatment（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:PLQT can enhance the limb movement， promote the vertebral artery flow volume and microcirculatory blood flow in the pia mater， improve the degree of imaging of the cervical spine， regulate the vasomotor function， and improve the coagulation and fibrinolysis system of CSA rats， which shows good potential for the treatment of CSA.

Expert consensus on clinical application of Wangbi Tablets in treating rheumatoid arthritis and knee osteoarthritis / 中国中药杂志

Wangbi Tablets are widely used in the treatment of rheumatoid arthritis, knee osteoarthritis and other diseases at pre-sent. Long-term clinical application and research have shown that this drug has a good effect in reducing the pain of related diseases and improving symptoms. Due to the lack of guidance in the instructions and currently no relevant norms to guide the clinical application of Wangbi Tablets, in order to further improve clinicians' understanding of the drug and fully tap the clinical advantages of the drug, the Professional Committee of Orthopedics and Traumatology Drug Research of China Association of Chinese Medicine organized experts in the fields of rheumatism, orthopedics, pharmacy and methodology in Chinese and western medicine to develop expert consensus on Chinese patent medicines in accordance with the relevant requirements of the consensus methodology. Based on full consideration of clinical research evidence and expert experience, the clinical issues were summarized in the consensus, and for those clinical problems supported by evidences, the internationally recognized recommendation evaluation and formulation method GRADE was used to evaluate the evidence and form recommendations; for those clinical issues not supported by evidences, a consensus was reached through the nominal group method to form consensus recommendations. The consensus adopted a concise and clear format to form re-commendations or reach consensus suggestions on the medication regimen, medication characteristics, intervention timing, usage and dosage, course of use and safety issues for the treatment of rheumatoid arthritis and knee osteoarthritis with Wangbi Tablets. It is suggested that its application will better improve the efficacy of Wangbi Tablets in the treatment of rheumatoid arthritis and knee osteoarthritis, at the same time provide a reference for clinicians to use Wangbi Tablets in a standardized, reasonable and safe manner.

Exploration on Biological Basis Underling Different Syndromes of Nontraumatic Osteonecrosis of Femoral Head Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.

Clinical Analysis of "Different Diseases Saring Same Syndrome" Concept in End Stage of Different Hip Diseases / 中国实验方剂学杂志

The traditional Chinese medicine (TCM) concept that "different diseases may share the same TCM syndrome" is a unique theory explaining the relationship between diseases and TCM syndromes, which originally means that different diseases sharing the same TCM pathogenesis may develop the same syndrome. It accords with the theory of treatment based on syndrome differentiation. In clinical practices, this concept explains why the same herbal formula can be used to treat different diseases. With the development of a novel strategy to integrate the disease diagnosis and TCM syndrome differentiation, the meaning of "different diseases may share the same TCM syndrome" has also changed. It means that different diseases share the same TCM pathogenesis during their progression may show the same syndrome. Osteonecrosis of the femoral head （ONFH）, hip osteoarthritis (HOA), and hip rheumatoid arthritis (HRA) are three different diseases that occur in the bones, cartilage, and synovium of the hip joint, respectively. However, they share similar clinical symptoms and TCM symptoms if they had progressed to the end-stage. In the end-stage of the disease, hip pain, restricted activity, signs of waist and knee pain, and weakened walking function, whether it is symptoms or signs or TCM syndromes, all show their similarities, reflecting the concept of different diseases may share the same TCM syndrome. This article discusses the similarity of the three diseases from the aspects of syndrome characteristics, radiographic findings, syndrome differentiation, etiology and pathogenesis, as well as clinical treatments. We found that, in addition to similar clinical signs and symptoms, the three hip osteoarthropathies in the end-stage see articular cartilage degeneration, joint space stenosis, joint effusion, synovial thickening, bone hyperplasia, and subchondral bone cystic degeneration, etc. similar X-ray performance， kidney sperm, bone marrow, only kidney sufficiency, muscles and bones can be filled with bone marrow, liver blood, main muscles, liver and blood are sufficient to support the muscles and bones, and the disease is in the advanced stage， ONFH， HOA and HRA are closely related to liver and kidney dysfunction. Insufficient liver and kidney, meridian muscle, and bone malnutrition are three common pathological mechanisms of late hip bone disease. Deficiency, waist and knee weakness, and weakness in walking have also become common symptoms. It not only provides a theoretical basis for the "same syndrome",but also helps the differential diagnosis of "different diseases", improves the fracture level of hip diseases, and enriches the connotation of "different diseases sharing the same syndrome" in Chinese medicine.

Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis / 中国中药杂志

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.

Study on the risk factors for the misdiagnosis of femoral head osteonecrosis / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the status and risk factors for the misdiagnosis of femoral head osteonecrosis, providing the basis for accurate diagnosis of osteonecrosis of femoral head.</p><p><b>METHODS</b>The data of 314 hospitalized patients were collected from March 2015 to March 2016, and the risk factors for osteonecrosis of femoral head were analyzed by Logistic regression model. Misdiagnosis was defined that the diagnosis given on the first time was different from that on the second time or that given by expert group with the same symptoms and signs. The general data, predisposing factors, time of onset, hospital visits, clinical manifestations, X-ray film of hip joint, MRI and other data were statistically analyzed.</p><p><b>RESULTS</b>Total 127 patients experienced misdiagnosis (up to 40.8%). Among them, the patients with osteonecrosis of femoral head misdiagnosed as other diseases accounted for 77.2% and the patients with other diseases misdiagnosed osteonecrosis of femoral head accounted for 22.8%. Statistical analysis showed that the predisposing factors, history of glucocorticoid and alcohol intake, diseased lower limb, pained lower limb, hidden disease attack, the level of first reception hospital and expert were significantly related with the misdiagnosis of femoral head osteonecrosis based on the logistic regression model (<0.05) . The relationship between misdiagnosis and gender, age, primary disease taking glucocorticoid, approach and time of glucocorticoid use, the type of alcohol, drinking time had no statistical significance(>0.05). The Logistic regression analysis showed that the hidden disease attack(OR=3.059) and level of first reception expert(OR=2.778) were the high risk factors associated with the misdiagnosis in which the femoral head necrosis was misdiagnosed as other diseases(<0.01), and glucocorticoid intake history was the low risk factors(OR=0.387)(<0.05). The Logistic regression analysis showed that the level of first reception expert (OR=3.573) was the high risk factor associated with the misdiagnosis in which the other diseases were misdiagnosed as necrosis of femoral head.</p><p><b>CONCLUSIONS</b>Misdiagnosis rate of femoral head necrosis is high. Hidden disease attack and low level of first reception expert are the high risk factors associated with the misdiagnosis in which the femoral head necrosis was misdiagnosed as other diseases, however, glucocorticoid intake history is the protective factor of misdiagnosis. Low level of first reception expert is the high risk factor associated with the misdiagnosis in which other diseases were misdiagnosed as necrosis of femoral head.</p>

Case-control study on Chinese medicine fumigation and massage therapy for the treatment of knee stability and func tional recovery after anterior cruciate ligament reconstruction operation / 中国骨伤

<p><b>OBJECTIVE</b>To study clinical outcomes of Chinese medidine fumigation and massage therapy for the treatment of knee stability and functional recovery after anterior cruciate ligament reconstruction operation,and to explore the effect on tendon-bone healing.</p><p><b>METHODS</b>Total 50 patients were divided into two groups: the control group (normal rehabilitation therapy group),the treatment group (Chinese medicine fumigation and manipulation group). There were 25 patients in the control group, including 16 males and 9 females, who were treated with isometric muscle training, with the gradually enlarging amplitude of flexion and progressive loading of bearing training for knee recovery. There were 25 patients in the treatment group, including 15 males and 10 females,who were treated with the conventional rehabilitation therapy combined with Chinese medicine fumigation and massage therapy. The Chinese herbs named as Haitongpi decoction was steamed by a special equipment to fumigate the knee after operation; Based on the biomechanical parameters of the ligament reconstruction, the massage therapy was designed to control the degree of the knee flexion and release the adhesion for early recovery of knee functions. The Lysholm knee function evaluation system was used, and MRI examination was performed to measure the change in width of ligament tunnel in femur and tibia to evaluate the safety and stability of the treatment.</p><p><b>RESULTS</b>Lysholm system showed that two groups both had improving results from the 1st month after operation to the 3rd month (treatment group, F=36.54, P<0.05; the control group, F=28.12, P<0.05), and the results of the treatment group was better than that of the control group at the observation point (the 1st month, t=0.105, P<0.05; the 3rd month, t=5.361, P<0.01). There was no difference between the two groups when evaluating the bone and tendon healing 3 and 12 months after operation (P>0.05), indicating that Chinese rehabilitation therapy was a safety treatment without the influence on the loosing of tendon.</p><p><b>CONCLUSION</b>Chinese medicine fumigation and massage therapy can early improve the knee function after the anterior cruciate ligament reconstruction operation without the disturbance of the knee stability.</p>

Study on optimization of a fewest layer measuring method of osteonecrotic area in femoral head / 中国骨伤

<p><b>OBJECTIVE</b>To optimize a measuring method of osteonecrotic area by analyzing the average osteonecrotic areas and osteonecritic volume using multi layer MR images.</p><p><b>METHODS</b>The MRI images of 87 cases (120 hips) of ONFH(ARCO II) were collected retrospectively from January 2011 to January 2012 in Wangjing Hospital of China Academy of Chinese Medicine Science. PHILIPS Achieval 1.5T MR was used to obtain coronal TSE T1 weighted (T1W) images. The scanning parameters were shown as follows:slice thickness, 3.5 mm; gap, 0.3 mm; images repetition time(TR), 500 ms;echo time(TE), 20 ms;field of view (FOV), 374 mm;total 12 layers. According to the distribution rule of osteonecrotic lesion, the layer of coronal T1-weighted imaging showing most of femoral neck was marked as layer 0(L0). The layers before L0 were marked in sequence L1, L2, L3, L4... , and the layers after L0 were marked in sequence L-1, L-2, L-3, L-4... . Auto CAD 2007 was used to measure the percentage of osteonecrotic area and calcu late the average data, and then decreased the layer from low to high layer successively based on frequency of osteonecrotic occurrences. First, the layer with lowest frequency of osteonecrotic occurrenoses L3 was removed, then calculated the average osteonecrotic area of the ramaining 8 layers. L5, L4, L-2, L-1, L3 layers were gradually removed, resulting in the calculation of avereage osteonecrotic areas in 7, 6, 5, 4, 3 layers. These areas were compared to the osteonecrotic volume in MR imagings, leading to the optimization of the fewest layer measuring method of osteonecrotic area using a statistical analysis.</p><p><b>RESULTS</b>The percentage of osteonecrotic volume in 120 hips was 0.333±0.151. The average osteonecrotic areas of 9 to 3 layers were 0.321±0.117, 0.317±0.136, 0.312±0.147, 0.333±0.153, 0.348±0.172, 0.365±0.174, 0.377±0.202 respectively. There were no statistical differences of the average osteonecrotic areas and osteonecrotic volume in 9 to 3 layers(>0.05), but when the osteonecrotic layers were reduced to 3, there were statistical differences(<0.05). Total 120 hips were grouped according to osteonecrotic volume based on ARCO staging criteria, among them, 12 hips were grade A, 43 were B, 65 were C. According to average osteonecrotic areas of 4 layers, 10 hips were A grade, 32 were B, 78 were C. There were no statistical differences between two methods(>0.05). There was a high degree of concordance among two methods.</p><p><b>CONCLUSIONS</b>The results of 4(L0, L1, L2, L3) layers measuring method and osteonecrotic volume measuring method are similar. The 4 layers measuring method is an accurate, convenient, valuable method measuring the esteonecrotic area with the fewest layers, which is worth to be popularized in clinical application.</p>

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.

Effect of Ermiao Recipe with medicinal guide Angelicae Pubescentis Radix on promoting the homing of bone marrow stem cells to treat cartilage damage in osteoarthritis rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Ermiao Recipe (, EMR) with medicinal guide Angelicae Pubescentis Radix (APR) on the homing of bone marrow stem cells (BMSCs) to focal zone in osteoarthritis (OA) rats.</p><p><b>METHODS</b>Forty-eight Sprague-Dawley rats were randomly assigned to the sham-operated, model, EMR, and EMR plus APR groups (12 rats in each group). The OA rat model was induced by anterior cruciate ligament transection and medial meniscus resection. All rats were injected with recombinant human granulocyte colonystimulating factor [rhG-CSF, 30 μg/(kg·d) for continuous 7 days], and rats in the EMR and EMR plus APR groups were treated with EMR or EMR plus APR at 1.6 or 1.9 g/(kg·d) for 3 or 6 weeks, respectively. Cartilage histopathologic changes were observed by hematoxylin and eosin staining. Chondrocytes apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Interleukin-1β (IL-1 β), tumor necrosis factor α (TNF-α), bone morphogenetic protein 2 (BMP-2), and transforming growth factor beta-1 (TGF-β1) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay assay. Matrix metalloproteinase (MMP)-13, tissue inhibitors of metalloproteinase (TIMP)-1, bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemistry assay.</p><p><b>RESULTS</b>EMR and EMR plus APR significantly inhibited articular cartilage damage and synovium inflammation in OA rats at 3 or 6 weeks of treatment, the most obvious changes in these parameters were found in the EMR plus APR group. At 6 weeks, compared with EMR treatment, EMR plus APR remarkably inhibited chondrocytes apoptosis and the release of IL-1β and TNF-α, obviously decreased MMP-13 expression, and significantly increased expressions of proteoglycan, collagen, type II collagen and TIMP-1, serum levels of BMP-2 and TGF-β1 as well as expressions of BrdU, CD34 and SDF-1 in cartilage articular (P<0.01 or P<0.05).</p><p><b>CONCLUSION</b>The medicinal guide APR improved the therapeutic effects of EMR on OA rats by promoting directional homing of BMSCs to focal zone.</p>

Treating early-to-middle stage nontraumatic osteonecrosis of femoral head patients by jianpi huogu recipe: a retrospective study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the efficacy and features of treating early-to-middle stage nontraumatic osteonecrosis of femoral head (NONFH) patients by Jianpi Huogu Recipe (JHR).</p><p><b>METHODS</b>Using retrospective paired control method, early-to-middle stage NONFH patients treated by JHR and followed-up for 2 years were recruited as the test group (47 cases). Those accepted surgery of core decompression, focus debridement and bone graft were recruited as the control group (48 cases). Radiographic images and clinical data of patients were collected before and after treatment. The stable rate and excellent rate of Harris score were taken as efficacy evaluation indicators.</p><p><b>RESULTS</b>(1) There was no statistical difference in excellent rate of Harris score between the two groups (95.74% vs. 79.17%, P > 0.05). But better effects were obtained in the test group in relieving pain, improving joint deformation, joint mobility, and total Harris score (P < 0. 05, P < 0. 01). There was no statistical difference in the stable rate of radiography between the two groups (74.47% vs. 75.00%, P > 0.05). (2) There was no statistical difference in the stable rate of radiography at phase II and Ill [staging by Association Research Circulation Osseous (ARCO)] between the two groups (82.05% vs. 80.00%, 37.50% vs. 50.00%, P > 0.05). (3) The stable rate of radiography and excellent rate of Harris score were obviously higher in ARCO phase II patients than in ARCO phase Il patients (82.05% vs. 37.50%,97.44% vs. 87.50%, P < 0.01).</p><p><b>CONCLUSIONS</b>Equivalent stable rate of radiography to that of surgery could be obtained in treating early-to-middle stage NONFH patients by JHR. But it was better than surgery in relieving pain, improving joint deformation and joint mobility.</p>

Effects of promoting blood circulation to remove meridian obstruction combined with medicinal guides on related osteogenesis factors in rabbits with femoral head necrosis / 中国骨伤

<p><b>OBJECTIVE</b>To observe effects of blood circulation promoting compounds combined with medicinal guides on content of bone glaprotein (BGP), bone morphogenetic protein-2 (BPM-2) and expression of BMP-2 mRNA in rabbits with femoral head necrosis, and explore its mechanism.</p><p><b>METHODS</b>Ninety-eight healthy Spragur-Dawley male rabbits were collected and weighted 2.2 to 2.8 kg. Eighty-four rabbits were built femoral head necrosis model by freezing left femoral head in liquid nitrogen, then randomly divided into 6 groups, 14 in each group. The 6 groups included model group,promoting blood circulation to remove meridian obstruction group,promoting blood circulation to remove meridian obstruction combined with achyranthes bidentata group,radix angelicae pubescentis, asarum group, and platycodon grandiflorum group,other 14 rabbits were sham operation group. While drug groups were administrated corresponding Chinese herb after molding,model group and shamp operation group were given saline. Recombinant human granulocyte-colony stimulating factor ( 30 microg x kg(-1) x d(-1))were injected into all rabbits for 7 days. Samples were taken on the second and fourth week,the content of BGP and BMP-2 were detected by enzyme-linked immunosorbent assay (ELSA) and radioimmunoassay (RIA), histopathological changes of left femoral head were observed by Hematoxylin and Eeosin staining (HE), and expression of BMP-2 mRNA were tested by fluorescence in situ hybridization.</p><p><b>RESULTS</b>Compared with sham operation group, the rate of empty lacunae femoral head were obviously increased in model group, and the content of BGP were increased on the second week, and BMP-2 and BMP-2 mRNA were decreased on the fourth week. Compared with model group, the content of BGP, BMP-2 and BMP-2 mRNA were higher both of the second and fourth week in promoting blood circulation to remove meridian obstruction group. The rate of empty la- cunae femoral head were lower in achyranthes bidentata group, BGP, BMP-2 and BMP-2 mRNA were higher on the fourth week. The rate of empty lacunae femoral head were lower in platycodon grandiflorum group, and BGP were decreased on the second and fourth week, BMP-2 were lower on the second week ,while BMP-2 mRNA were decreased on the fourth week; the content of BMP-2 and BMP-2 mRNA were increased in radix angelicae pubescentis group on the second week; while there was no change in asarum group.</p><p><b>CONCLUSION</b>Radix angelicae pubescentis can increase the content of BGP, BMP-2 and expression of BMP-2 mRNA ,which is an effective mechanism of preventing femoral head necrosis.</p>

Effects of huogu I formula (I) on correlated factors of bone regeneration in chickens with steroid-induced necrosis of femoral head / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the mechanism of Huogu I formula (I) in treating osteonecrosis of femoral head.</p><p><b>METHODS</b>Forty-eight healthy female Leghorn chickens were randomly divided into control group, model group and Huogu I group, and each group consisted of 16 chickens. At the meantime of model establishment, chickens of the Huogu I group were administrated with decoction, while the model and control group with distilled water by gavage. At the 8th and 16th week after medication, blood samples were obtained for blood lipid detection while both sides of femoral head were harvested for the rest of examinations. Specifically, expressions of bone morphogenetic protein-2 (BMP2), transforming growth factor beta1 (TGFβ(1)), Smad4 and Smad7 were evaluated by immunohistochemistry, while expression of osteoprotegerin/receptor activator of nuclear factor kappaB ligand (OPG/RANKL) mRNA was detected by in situ hybridization.</p><p><b>RESULTS</b>Compared with the control group, serum levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the model group rose significantly. Positive cell counting of BMP2, TGFβ(1), Smad4 and OPG in femoral head of the model group dropped prominently. Positive cell counting of Smad7 and RANKL increased dramatically. In contrast with the model group, levels of TC, TG and LDL-C in Huogu I group reduced significantly. Positive cell counting of BMP2, TGFβ(1), Smad4 and OPG in femoral head of the Huogu I group increased prominently. Indices of Smad7 and RANKL both decreased significantly. Especially at the 8th week, these variations were more significant.</p><p><b>CONCLUSION</b>Huogu I formula is effective in promoting repair of necrotic femoral head by regulating the expressions of BMP2, TGFβ(1), Smads and OPG/RANKL of osteoclast in femoral head.</p>

Effect of Huogu II Formula (II) with medicinal guide Radix Achyranthis Bidentatae on bone marrow stem cells directional homing to necrosis area after osteonecrosis of the femoral head in rabbit / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Huogu II Formula (II) with medicinal guide Radix Achyranthis Bidentatae (Ach) on bone marrow stem cells (BMSCs) homing to necrosis area after osteonecrosis of the femoral head (ONFH) frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH.</p><p><b>METHODS</b>The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/(kg·day) for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells (WBC) were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2nd and 4th weeks after model built; bone glutamine protein (BGP) and bone morphogenetic protein 2 (BMP2) levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin (HE) staining. BMP2 mRNA levels were detected with in situ hybridization (ISH) staining. 5-Bromo-2'-deoxyuridine (BrdU) and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemical assay in femoral head of the left hind leg.</p><p><b>RESULTS</b>Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obvious in Huogu II plus Ach group. BGP and SDF-1 on the 2nd week and empty lacuna rate and serum BMP2 level on the 4th week in Huogu II group significantly exceeded their counterparts. On the 2nd week, only in Huogu II plus Ach group that the BrdU counting rose significantly. On the 4th week, empty lacuna rate and serum BMP2 level in Huogu II plus Ach group exceeded those in Huogu II group distinctively.</p><p><b>CONCLUSIONS</b>To a certain extent, the medicinal guide Ach improves the preventive and therapeutic effects of Huogu II Formula on experimental ONFH model. The possible mechanism of this is related to its promoting effect on directional homing of BMSCs to the necrosis area.</p>

Experimental research progress of warming yang and reinforcing kidney of Chinese medicine to promote the differentiation of bone marrow stromal cells / 中国骨伤

Bone marrow stromal cells (BMSCs), a kind of stem cells residing in bone marrow, have self-renewal, high proliferative capacity and the potential of multilineage differentiation. It has a good prospect in application of the cell replacement therapy, the gene therapy and the tissue engineering and so on. As the content of BMSCs is extremely low in bone marrow, BM-SCs must be amplified in vitro and induced to differentiation to meet the clinical needs. Researches of the recent years suggest there is a very promising way that Chinese medicine could induce BMSCs proliferation, differentiation. Based on the Chinese medicine theory, "the kidney generating marrow and dominating bone" and "kidney storing essence, essence and marrow", the TCM scholars have done some researches to explore the function of warming yang and reinforcing kidney of Chinese medicine to promote bone marrow stromal cells and found that these drugs can promote the BMSCs to proliferate and to differentiate into osteogenic, cartilage and nerve cells. This article elaborates and presents the researches on this aspect.

Experimental study on avascular necrosis of femoral head in chickens induced by different glucocorticoides / 中国骨伤

<p><b>OBJECTIVE</b>To study the effects of Methylprednisolone and Dexamethasone on the avascular necrosis of femoral head in chickens.</p><p><b>METHODS</b>Thirty-six chickens were randomly divided into 6 groups (n = 6): control group (group A), Methylprednisolone low dose group (group B), Methylprednisolone large dose group (group C), small dose Dexamethasone and horse serum group (group D), middle dose Dexamethasone and horse serum group (group E), and Dexamethasone large dose group (group F). On the 6th and 12th weeks, blood samples were obtained to determine the level of total cholesterol triglyeride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). On the 12th week, femoral heads were taken off. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin staining.</p><p><b>RESULTS</b>On the 6th week, compared with group A, the level of CHO increased significantly in group C and group F (P < 0.05), and TG increased in group B, C and group E, while HDL decreased in group B, C and group E. On the 12th week, the level of TG and CHO increased in group B, C, E and group F, and HDL decreased in group C, D and group E (P < 0.05). LDL was not detected in most chickens. The ratio of empty lacuna was higher in group C and group E compared with those of the control group (P < 0.05).</p><p><b>CONCLUSION</b>Methylprednisolone is easier to induce osteonecrosis of femoral head than Dexamethasone. The condition of metabolic disorder in blood may be the basic pathomechanism of steroid-induced necrosis of femoral head.</p>

Protective effects of omega-3 fish oil on lead-induced impairment of long-term potentiation in rat dentate gyrus in vivo / 生理学报

In order to evaluate the effect of omega-3 fish oil supplement by gavage (0.4 mL/100 g body weight) on the chronic lead-induced (0.2% lead acetate) impairments of long-term potentiation (LTP) in rat dentate gyrus (DG) in vivo, we designed the experiments which were carried out in four groups of newborn Wistar rats (the control, the lead-exposed, the control with fish oil treatment and the lead-exposed with fish oil treatment, respectively). The excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG of rats with above different treatments at the age of 80-90 d in response to stimulation applied to the lateral perforant path. The results showed (1) postnatal chronic lead-exposure impaired LTP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; (2) in the control rats, omega-3 fish oil had no effect on LTP while in the lead-exposed rats, omega-3 fish oil had a protective effect on LTP. These results suggest that omega-3 fish oil supplement could protect rats from the lead-induced impairment of LTP. Omega-3 fish oil might be a preventive substance in reducing LTP deficits induced by lead.