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.

[Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Tripterygium wilfordii Hook.f.(TwHF) is one of the most effective traditional Chinese herbal medicines against rheumatoid arthritis. As the representative agents of TwHF, Tripterygium Glycoside Tablets(TGT) and Tripterygium wilfordii Tablets(TWT) were included as Class A drugs in the 2019 edition of Medicine Catalogue for National Basic Medical Insurance, Injury Insurance and Maternity Insurance, and TGT was also included in 2018 edition of National Essential Drug List and 2015 edition of Chinese Pharmacopoeia. However, it is difficult to grasp the specific clinical applications of TGT and TWT. Side effects occur from time to time. The curative effect is uneven in patients. And the package inserts of TGT and TWT are not described in details. In order to standardize the clinical application of Tripterygium wilfordii preparations, 38 authoritative units and 48 well-known experts in rheumatoid immunology clinical department, drug supervision and management, pharmacy and evidence-based medicine research fields jointly developed Tripterygium Glycoside Tablets and Tripterygium wilfordii Tablets Medication Guide for reference in clinical application, teaching and scientific research. The guideline followed the "evidence-based, consensus-assisted and experience-based" principles to form "recommendations" for the evidence supported ones, and form "consensus suggestions" for those without evidence support by using nominal group method. In this way, the medication recommendations on function, usage and dosage, drug combinations, precautions, efficacy, safety and other aspects of TGT and TWT can be provided. The application of this Guide will help to avoid or reduce the adverse reactions of T. wilfordii preparations, enhance the efficacy and reduce the cost of medicine, with certain demonstration and promotion values to improve the rational use level of traditional Chinese medicine.

[Editorial explanation for Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the treatment of rheumatoid arthritis(T/CACM 1337-2020) was approved on June, 2020 by the Standardization Office of Chinese Association of Chinese Medicine. Our group developed this guideline for the clinical application of Tripterygium Glycosides/Tripterygium wilfordii Tablets according to the manual for the clinical experts consensus of Chinese patent medicine from January, 2018, when this project was approved by Chinese Association of Chinese Medicine. In this article, the detailed information on our compilation process was provided, in order to facilitate the understanding and the application of the guideline, as well as provide reference for the development of clinical practice guideline for other Chinese patent medicine.

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.

Effect of An-pressing manipulation on post-stroke muscle spasticity in rats and its mechanism study / 针灸推拿医学（英文版）

Objective: To explore the mechanism of An-pressing manipulation in improving post-stroke muscle spasticity, by observing the changes of γ-aminobutyric acid (GABA) and glycine (Gly) in plasma and gray matter of L1-L3 spinal cord anterior horn in post-stroke rats with muscle spasticity after An-pressing manipulation intervention. Methods: Ten of 80 adult male Sprague-Dawley (SD) rats were randomly selected as the blank group, and the remaining 70 were used for modeling. The middle cerebral artery occlusion (MCAO) rat model was established by insertion suture occlusion method in the left external carotid artery. Thirty rats with a Longa neurological score of 2-3 points and a modified Ashworth spasticity scale score of 1-, 1+, or 2 were included in the experiment. Using the random number table method, the 30 successfully modeled rats were randomly divided into a model group, an An-pressing tendon group and an An-pressing muscle belly group. Two days after modeling, rats in the An-pressing tendon group and An-pressing muscle belly group received An-pressing manipulation on the tendon and belly of quadriceps femoris muscle respectively, with the pressure of (350±50) g and the frequency of 5 s/time, 15 min per session, once a day for 5 continuous days. After the 5th treatment, the tension of the rat quadriceps femoris muscle was evaluated using the modified Ashworth spasticity scale. The Gly levels in rat plasma and L1-L3 segments of spinal cord were determined by enzyme-linked immunosorbent assay (ELISA). The GABA levels in rat plasma and L1-L3 segments of spinal cord were measured by high performance liquid chromatography (HPLC). Results: The decrease in rat muscle tension scored by the modified Ashworth spasticity scale in the An-pressing tendon group was more significant than that in the An-pressing muscle belly group (P<0.01); the increases in Gly and GABA levels in the rat plasma and L1-L3 segments of spinal cord were more significant in the An-pressing tendon group than those in the An-pressing muscle belly group (all P<0.01). Conclusion: Based on the theory of 'anti-stretch reflex' of tendon organs, the use of An-pressing manipulation to induce the 'anti-stretch reflex' by stimulating the tendon organs can improve the muscle spasticity of rats, which is better than An-pressing the muscle belly. Increased levels of Gly and GABA in rat plasma and L1-L3 segments of spinalcord may be one mechanism of An-pressing manipulation to improve muscle spasticity by stimulating tendon organs.

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.

Effects of needling acupoints at different nerve segments on oxytocin neurons in rat's hypothalamic paraventricular nucleus and intragastric pressure / 针灸推拿医学（英文版）

Objective:To compare and explore the effects of needling acupoints at different nerve segmentson the oxytocin (OT) neurons in the paraventricular nucleus of hypothalamus (PVN) and the intragastric pressure, and discuss the possible mechanisms. Methods: Thirty-two healthy adult Sprague-Dawley (SD) rats were numbered and divided into 4 groups according to the random number table, a Zusanli (ST 36) group, a Neiguan (PC 6) group, a Weishu (BL 21) group and a control group, with 8 rats in each group. Except the control group, rats in the other three groups received acupuncture at the corresponding acupoints. To observe the differences in double-labeled OT neurons and c-fos neurons of the hypothalamic PVN and the intragastric pressure after acupuncture among the three groups of needling acupoints at different nerve segments. Results:Compared with the control group, the numbers of double-labeled cells in the PVN of the Zusanli (ST 36) group and the Neiguan (PC 6) group decreased significantly, while the intragastric pressure increased significantly (allP<0.05), and the inter-group differences were statistically significant (P<0.05). The intragastric pressure in the Weishu (BL 21) group decreased significantly, and the inter-group difference was statistically significant (P<0.05). Compared with the Weishu (BL 21) group, the numbers of OT/c-fos double-labeled cells in PVN of the Zusanli (ST 36) group and the Neiguan (PC 6) group decreased significantly, and the intragastric pressure increased significantly, the inter-group differences were statistically significant (allP<0.01). Conclusion:Acupoints at different nerve segments have different regulation effects on intragastric pressure. The difference may be related to the different nerve conduction pathways by acupoints at different nerve segments in regulating the intragastric pressure. The PVN may be one common integration center for the regulation of gastric function in the three acupoints [Zusanli (ST 36), Neiguan (PC 6) and Weishu (BL 21)] at different nerve segments.

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.

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>

Gastric distention-related neurons in dorsal nucleus of the vagus nerve of rats in response to different acupuncture acupoints / 中国组织工程研究

BACKGROUND:Preliminary studies of our research group mainly focus on the role of nucleus of solitary tract in gastric noxious stimulation and acupuncture point, while dorsal nucleus of vagus nerve, nucleus of solitary tract and area postrema are the necessary component for vagus nerve complex, and dorsal nucleus of vagus nerve plays a crucial role in the regulation of gastric functions. OBJECTIVE:To observe the effect of acupuncture at Zusanli, Neiguan, Pishu and Shenshu acupoints on the gastric-related neurons in dorsal motor nucleus of the vagus nerve. METHODS:The gastric related neurons in dorsal motor nucleus of the vagus nerve of gastric distension rats were identified using extracellular recording technique, according to neuroelectrophysiology method. Acupuncture stimulation was given to Zusanli, Neiguan, Pishu and Shenshu for 15 seconds. The effect of body stimulation on the gastric distension related neurons in dorsal motor nucleus of the vagus nerve of rats was recorded. RESULTS AND CONCLUSION:Among the involved 24 rats, 90 neurons at paraventricular hypothalamic necleus exhibited discharge. Among the discharged neurons, 54 neurons were related to gastric distension. After acupuncture stimulation at Zusanli, Neiguan, Pishu and Shenshu, there were 44, 39, 38, 27 neurons giving a response, the reaction rate was 82%, 72%, 70%and 50%, respectively. Acupunture at different nerve segment acupoints can activate the dorsal motor nucleus of the vagus nerve to different degrees, which is involved in the regulation of gastric motility.

Response of gastric-related neurons in the hypothalamic paraventricular nucleus to acupuncture at Neiguan and Zusanli in a rat model of gastric distension / 中国组织工程研究

BACKGROUND:Previous studies concerning neuromechanism of acupuncture for regulating gastric function mainly focused on peripheral nerve, involving in central nervous system. In particular, there are few studies addressing higher central nervous system. OBJECTIVE:To explore the effects of acupuncture at Neiguan (PC6) and Zusanli (ST36) on gastric-related neurons in the hypothalamic paraventricular nucleus. METHODS:Using microelectrode extracellular recording technique, gastric related neurons in the paraventricular nucleus were found in gastric distension rats. Stimulation was conducted for 30 seconds by hand acupuncture at Neiguan and Zusanli. The effects of acupuncture on gastric-related neurons in the paraventricular nucleus were observed. RESULTS AND CONCLUSION:The discharge of 109 neurons in the hypothalamic paraventricular nucleus of 60 rats was recorded. A total of 56 gastric-related neurons of the 109 neurons were observed. The number of neurons response to acupunctures at Zusanli, Neiguan, Pishu (BL20) and Weishu (BL21) were respectively 44, 47, 29, and 33, with the reaction proportion of 78.57%, 83.47%, 51.79%and 58.93%. Results suggested that there exist gastric distension stimulation and acupuncture stimulations from neurons soma to visceral reaction in the hypothalamic paraventricular nucleus, which simultaneously participates in the regulation of acupuncture on the gastric function.

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>

Screening of specific microRNA in hippocampus of depression model rats and intervention effect of Chaihu Shugan San / 中国中药杂志

<p><b>OBJECTIVE</b>To screen microRNAs with specific expression of in hippocampus of rats with chronic stress induced depression model, and observe the effect of traditional Chinese medicine Chaihu Shugan San on the expression of microRNA in hippocampus.</p><p><b>METHOD</b>SD rats were randomly divided into 3 groups: the normal control group, the model control group and the Chaihu Shugan San group. The depression model was replicated by unpredictable chronic mild stress combined with separation. Behavioral changes of the rats were observed by Open-field test and sucrose solution consumption test, and the expression of microRNAs in hippocampus was assayed by microRNA micro-array.</p><p><b>RESULT</b>Compared with the normal control group, there were 13 specific miRNAs in hippocampus in the model control group with the expression difference of more than 2 times. Among them, down-regulating miRNAs included miR298, miR-130b, miR-135a, miR-323, miR-503, miR-15b, miR-532, and miR-125a, and the up-regulation miRNAs included miR7a, miR-212, miR-124, miR-139, and miR-182. Among the 13 specific miRNAs, miR-125a and miR-182 recovered to normal after intervention with Chaihu Shugan San in the Chaihu Shugan San group.</p><p><b>CONCLUSION</b>This study preliminarily found that 13 specific miRNAs in hippocampus are related to depression. Among them, miR-125a and miR-182 recover to normal after intervention with Chaihu Shugan San, which may be the target points of the antidepressant effect of Chaihu Shugan San. We shall further analyze the target genes and their mechanisms.</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>

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>

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>

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.

Effects of different Chinese drugs on bone histomorphology of hormone induced femoral head necrosis / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate and compare the histopathology effects and mechanisms of the methods of "invigorating spleen to remove phlem & promoting blood circulation to remove meridian obstruction" and "invigorate the kidney & promoting blood circulation to remove meridian obstruction" preventing hormone induced femoral head necrosis in hens.</p><p><b>METHODS</b>Sixty-four healthy hens were randomly divided into 4 groups: blank control group, model group, Jianpi group (with therapeutics of invigorating spleen to remove phlem), Bushen group (with the effect of warming kidney for duresis). All hens were injected intramuscularly with Medrat once a week for 16 weeks but normal saline in blank control group. Bilateral femoral heads were dissected on 8 weeks or 16 weeks. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin, or mason staining.</p><p><b>RESULTS</b>Histological analysis showed that Huogu recipe I and Huogu recipe II can promote osteogenesis and repair osteonecrosis, increase blood circulation of bone marrow, and inhibit pimelosis of bone marrow. Compared with blank control group, the areas of adipose cells increased significantly (t = -12.9, P < 0.01), the area of immature collagen increased significantly (t = -2.0, P < 0.05) and the ratio of empty lacuna in medullary cavity (t = -3.7, P < 0.05). Compared with model group, both the area of adipose cells and the ratio of empty lacuna decreased in Jianpi group and Bushen group (F = 26.8, 13.5, P < 0.01), so it was with the Bushen group immature collagen (F = 4.6, P < 0.01).</p><p><b>CONCLUSION</b>Both the methods of "invigorating spleen to remove phlem & promoting blood circulation to remove meridian obstruction" and "invigorate the kidney & promoting blood circulation to remove meridian obstruction" can prevent hormone induced femoral head necrosis. The time taking effect in the method of "invigorating spleen to remove phlem" was shorter.</p>