Mechanism of Tongbi Jiangu Prescription in Treatment of Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Tongbi Jiangu prescription （TBJG） in the treatment of knee osteoarthritis （KOA） based on network pharmacology and molecular docking，and further verify it by cell experiments. MethodThe active components and the corresponding targets of TBJG were screened out according to the traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP）. The targets of KOA were obtained from GeneCards，online mendelian inheritance in man（OMIM）， and DrugBank. The common targets of active components of TBJG and KOA were the targets of TBJG against KOA. The active component-target network and protein-protein interaction （PPI） network were constructed by Cytoscape 3.7.2. STRING was used for PPI network analysis. DAVID was used for gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses. Key targets and core active components were selected for molecular docking by AutoDock. The results of network pharmacology were verified by cell experiments and the pharmacodynamic responses were observed. ResultThe prediction of network pharmacology showed that there were 111 active components of TBJG in the treatment of KOA. The core active components were quercetin，kaempferol， and β-sitosterol，and the key targets were interleukin-1β（IL-1β）， matrix metalloproteinase-3 （MMP-3），and tumor necrosis factor-α （TNF-α）. Biological processes （BP） in GO analysis mainly involved inflammatory response，response to lipopolysaccharide，apoptosis signaling pathway，and regulation of DNA activity in binding transcription factor. Cellular components （CC） included plasma membrane protein complex，RNA polymerase Ⅱ transcription factor complex，membrane raft，and serine/threonine protein kinase complex. Molecular functions （MF） were mainly enriched in cytokine receptor binding，nuclear receptor activity，protein domain specific binding，serine hydrolase activity，chemokine receptor binding，and activity of nitric oxide synthase regulator. As revealed by the KEGG analysis， the relevant signaling pathways were nuclear factor（NF）-κB， Janus kinase（JAK）/signal transducer and activator of transcription（STAT）， and Wnt signaling pathways. Molecular docking results showed that the core active components had good binding activities with key targets. The experimental results showed that TBJG could down-regulate IL-1β， MMP-3，TNF-α， and NF-κB p65 expression levels （P<0.05），and up-regulated NF-κB inhibitor（IκB）-α（P<0.05）. ConclusionThe mechanism of TBJG in the treatment of KOA lies in the application of active components such as quercetin，kaempferol， and β-sitosterol with IL-1β，MMP-3， and TNF-α as key targets through the NF-κB，JAK/STAT， and Wnt signaling pathways.

Interpretation of Expert consensus on Shujin Jianyao Pills in clinical practice / 中国中药杂志

Shujin Jianyao Pills is a kind of concentrated honey pills made of 13 Chinese herbal medicines, such as Cibotii Rhizoma, Rosae Laevigatae Fructus, and Spatholobi Caulis. It has the effects in tonifying liver and kidney, strengthening muscles and bones, removing wind and dampness, activating collaterals and relieving pain. Under the leadership of the Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences and Wangjing Hospital of China Academy of Chinese Medical Sciences, the Expert consensus on clinical application of Shujin Jianyao Pills was developed by 22 universities, scientific research institutes and hospitals. This consensus formed 1 recommendation and 9 consensus suggestions, which were based on evidence and oriented to clinical practice. The expert consensus had a new understanding of the indications of Shujin Jianyao Pills, especially the applicable Western medicine diseases, the advantages and characteristics of treatment, the time of intervention, the applicable syndromes, the precautions and contraindications of medication. The indications were detailed and expressed as the combination of disease, symptom and syndrome. And it filled in the gaps of package inserts in applicable syndrome and special population medication in the process of drug use. The expert consensus showed the optimization of precautions and contraindications, and more detailed description of drug safety. Therefore, it provides guidance and reference for clinicians to use Shujin Jianyao Pills rationally.

Expert consensus on Shujin Jianyao Pills in clinical practice / 中国中药杂志

Shujin Jianyao Pills is a Chinese patent medicine, with anti-inflammation, analgesic and anti-osteoporotic effects. Based on a questionnaire investigation of clinicians and a systematic review of study literatures on Shujin Jianyao Pills, the international clinical practice guidelines development method was adopted to analyze the optimal available evidences and expert experiences in the "evidence-based, consensus-based and experience-based" principles. Expert consensus on Shujin Jianyao Pills in clinical practice(GS/CACM267-2019) was developed by more than 30 multidisciplinary experts nationwide with the aim to guide and standardize the rational use of Shujin Jianyao Pills among clinicians and improve the clinical efficacy and safety. The expert consensus adopted the internationally recognized recommendation criteria for classification of evidence--GRADE. Expert consensus was formed by the nominal group method. Six main considerations were quality of evidence, curative effect, safety, economical efficiency, patient acceptability and other factors. If there were sufficient evidences, a "recommendation" was given, and GRADE grid voting rule was adopted. If there wasn't sufficient evidence, a "consensus opinion" was formed, and the majority counting rule. According to the indication, usage and do-sage, drug use for special population and safety of Shujin Jianyao Pills, one recommendation and nine consensus opinions were put forward. By means of expert meetings and correspondence, a nationwide consultations and peer reviews were conducted. This consensus is applicable to clinicians in hospitals and grass-roots health services, and provides guidance and reference for the rational use of Shujin Jianyao Pills.

Preparation instructions for Experts consensus statement on Cheezheng Xiaotong Tiegao in clinical practice / 中国中药杂志

As a topical plaster developed by modern pharmaceutical technology based on traditional Tibetan medicine,Cheezheng Xiaotong Tiegao has functions of promoting blood circulation,relieving swelling and relieving pain. Since its introduction in 1993,it has been widely used in the treatment of various types of acute and chronic musculoskeletal pain and various types of spinal,joint and soft tissue diseases. In order to better standardize the clinical application and improve the clinical efficacy of Cheezheng Xiaotong Tiegao,the research and development work of the Experts consensus statement on Cheezheng Xiaotong Tiegao in clinical practice was officially launched on October 19,2017,upon approval from China Association of Chinese Medicine. In this paper,main R&D process and related technical links for the experts consensus on Cheezheng Xiaotong Tiegao would be summarized,which will help the various medical workers understand,master and apply more accurately,and also provide reference for the development of experts consensus on clinical application of other topical Chinese medicines.

The Observation on the Effect of Q-Switching Nd:YAG Treatment in Pigmented Dermatoses and Influence for Melanin Metabolism / 昆明医科大学学报

Objective To observe the effect of Q-Switching Nd:YAG treatment in pigmented dermatoses and its influence for melanin metabolism. Methods 114 patients with pigmented dermatoses in our hospital from October 2015 to August 2016 were selected as the study object,and were randomly divided into the control group (57 cases) and the observation group (57 cases).The control group were treated with intense pulsed light therapy while the observation group were treated with Q-Switching Nd:YAG treatment on the treatment of control group. Then the total effective rates,recurrence rates,adverse reaction rates,skin lesion scores and serum melanin metabolism related indexes before and after the treatment of two groups were analyzed and compared. Results Clinically, the total effective rates of observation group were higher than those of control group ( <0.05)and the recurrence rate of observation group was lower than that of control group ( <0.05) .The adverse reaction rates of two groups were compared and the differences were not statistically significant ( >0.05) .The skin lesion scores and serum melanin metabolism related indexes of two groups before the treatment were compared and the differences were not statistically significant (>0.05) .The serum melanin metabolism related indexes of two groups after the treatment were all better than those of control group ( <0.05) . Conclusion The clinical effect of Q-Switching Nd:YAG treatment in the patients with pigmented dermatoses is better, and it has the active influence for the melanin metabolism,so it has higher clinical value in the treatment of pigmented dermatoses.

The therapeutic effects of Yougui pill on knee osteoarthritis and the expression of Wnt signal pathway related factors in rats / 中国应用生理学杂志

OBJECTIVES@#To observe the effects of Yougui pill (Traditional Chinese Medicine) on the related factors of Wnt signal pathway of rats with knee osteoarthritis (KOA), and explore its protective mechanism.@*METHODS@#Sixty SPF SD rats were randomly divided into the sham-operative group, model group, glucosamine sulfate group, high-dose, middle-dose, low-dose of Yougui pill treated group (=10). KOA model was established by modified Hulth method for six weeks. The rats in the high, middle and low-dose of Yougui pill group were treated with Yougui pills at the doses of 20,10 and 5 g/kg respectively by gastrogavage once a day for 8 weeks, while equal volume of normal saline was given to those in the sham and model control group and an equal volume of glucosamine sulfate (1.7 g/kg·d) was given to those in glucosamine sulfate group for 8 weeks. The knee joint was removed after the last dose of drug. The pathological changes of cartilaginous tissues were observed under a microscope. The mRNA levels of Dickkopf homolog 1(DKK1), Wnt induced secreted protein 1(WISP1), Wnt1, low density lipoprotein receptor related protein 5(LRP5) and beta -catenin in rats cartilaginous tissues were analyzed by using RT-PCR method, and the protein contents of DKK1, WISP1, Wnt1, LRP5 and beta-catenin in cartilaginous tissues were detected by Western blot.@*RESULTS@#Compared with the sham group, the articular cartilage was severely damaged, the Mankin score was increased significantly (<0. 05), the mRNA and protein expression levels of DKK1 in cartilaginous tissue were markedly decreased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were increased significantly in model group(<0.05). Compared with model group, the articular cartilage lesions was light (<0.05), the Mankin Score was decreased significantly(<0.05), and the mRNA and protein levels of DKK1 in cartilaginous tissue were increased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were decreased in Yougui pill high-dose group and glucosamine sulfate group (<0.05).@*CONCLUSIONS@#Yougui pill has protective effects on the KOA by inhibiting the expressions of WISP, Wnt1, LRP5, beta-catenin and increasing the expression of DKK1 cytokine in the Wnt signaling pathway.

Study on impact of ethanol extracts from Sedum sarmentosum in inhibiting STAT-3 signaling and inducing apoptosis of human hepatocellular carcinoma cell line HepG2 / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the impact of ethanol extracts from Sedum sarmentosum (ESB) on STAT-3 signaling and its probable molecular mechanism in inducing apoptosis.</p><p><b>METHOD</b>MTT assay was used to detect the impact of ESB on HepG2 cell proliferation. FITC-Annexin V-FITC /PI double-labeling were used to investigate the impact on hepatoma carcinoma cell apoptosis. Western blot analysis was used to test the expression levels of cell apoptosis-related proteins Caspase-3, Caspase-9, PARP, P-STAT-3 (Tyr705) , STAT-3, Bcl-2, Mcl-1.</p><p><b>RESULT</b>ESB could notably inhibit proliferation of HepG2 cells, and induce HepG2 cell apoptosis, with the dose-dependent inhibitory effect. In addition, ESB could inhibit STAT-3 signaling, down-regulate Mcl-1 and Bcl-2 expressions, and induce degradation/activation of apoptosis-related proteins Caspase-3 and Caspase-9 and PARP degradation in a dose-dependent manner.</p><p><b>CONCLUSION</b>ESB inhibits HepG2 cell proliferation and induces apoptosis by inhibiting STAT-3 signaling and Mcl-1 and Bcl-2 expressions.</p>

Case-control study on therapeutic effects of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries / 中国骨伤

<p><b>OBJECTIVE</b>To observe the effects of Chinese herb of promoting blood circulation to dissipate blood stasis on the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum of patients with mudslide injuries, and investigate the mechanisms of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries.</p><p><b>METHODS</b>Patients with mudslide injuries who were translated from Zhouqu and Chengxian to Lanzhou from 12th August 2010 were divided into two groups (group A and group B). Twenty-five patients in group A, containing 15 males and 10 females, with an average age of (39.0 +/- 3.9) years. According to AIS scoring system, 1 point in 2 cases, 2 points in 3, 3 points in 17 and 4 points in 3. No patients got 5 points. Based on ISS rating system, 16 cases got 16 points or less, 7 cases rated between 16 and 25, only 2 cases were equal to 25 points or more. Another 25 patients were in group B, including 11 males and 14 females, with a mean age of (40.1 +/- 3.6) years; AIS score showed 3 cases got 1 point, 4 got 2 points, 16 got 3 and 2 got 4 points, no patients got 5 points. Patients in group B were divided into three parts by ISS score:15 cases (16 points or less); 9 cases (range 16 to 25 points) and 1 case (25 points or more). All the patients accepted general physical checkup. Eight patients were treated by surgical treatment in group A (3 patients were treated with open reduction plate fixation, 4 patients were treated with debridement BHID, and 1 patient underwent foreign body removal) and 6 cases in group B (1 patient was treated with craniocerebral surgery,2 patients were treated with chest surgery, and 3 patients were treated with soft tissue debridement). All the patients of two groups were treated by support treatment, detumescence treatment and preventing infection, complications. A seven days course of treatment with detumescence analgesic mixture 50 ml p.o. bid, traumatologic cleansing liquid 20 ml ad us, ext 20 to 30 min qid to group A,continuous treatment of two courses. Using immunometric assay to determine serum levels of inflammatory cytokine TNF-alpha, IL-6 at the 2nd, 7th, 14th days after admission. Analysis of data were done with the help of SPSS 16.0 statistic software.</p><p><b>RESULTS</b>There were no statistical differences of TNF-alpha, IL-6 between two groups at the second day after admission, and there were statistical differences at the 7th and 14th days between two groups. There were significant differences of TNF-alpha and IL-6 levels between the 7th day and the 2nd day, the 14th day and 2nd day after admission.</p><p><b>CONCLUSION</b>The Chinese herb of promoting blood circulation to dissipate blood stasis can inhibit the release of inflammatory factor after traumatism.</p>

Clinical study on the prevention of heterotopic ossification after total hip arthroplasty by Xiaozhong Zhitong / 中国骨伤

<p><b>OBJECTIVE</b>To explore the therapeutic effects of Xiaozhong Zhitong mixture preventing heterotopic ossification (HO) after total hip arthroplasty.</p><p><b>METHODS</b>From July 2006 to October 2009, 154 patients underwent total hip replacement surgery were randomly divided into sham group (group A, 50 cases), indomethacin group (group B, 55 cases) and Xiaozhong Zhitong mixture group (group C, 49 cases). Among 154 patients, 9 cases were primary osteoarthris, 34 cases osteoarthritis secondary to acetabular dysplasia, 98 cases osteoarthritis secondary to avascular necrosis of the femoral head, 2 cases rheumatoid arthritis, 5 cases femoral neck fracture, 6 cases other diseases. Modified Gibson approach was used during the operation. After operation, group A was no preventing treatment, group B was treated by indomethacin 50 mg every time, twice a day; group C was treated by Xiaozhong Zhitong mixture 50 ml every time, twice a day for 4 weeks. Eighteen months after operation was study termination point and X-ray (including the double hip anteroposterior,obturator oblique and iliac oblique film) was used to observe whether heterotopic ossification was formed (Brooker classification was used to evaluate ossification degree); Harris scoring was used to evaluate the function of hip joint,including PAHSS 80 scores and IAHSS 20 scores.</p><p><b>RESULTS</b>All the patients were followed up,with the average of duration of 21.2 months. The condition of heterotopic ossification: for group A,there were 27 cases with heterotopic ossification(54%) ,and Brooker I in 8 cases, II in 9 cases, III in 8 cases and IVin 2 cases; for group B, there were 12 cases heterotopic ossification (21.82%), and Brooker I in 10 cases, II in 2 cases; for group C, there were 11 cases heterotopic ossification(22.45%), and Brooker I in 9 cases, I in 2 cases. There was significant difference among three group in heterotopic ossification by rank test (P<0.05), but no difference between group B and C (P>0.05); there were no significant difference among three groups before treatment in Harris, PAHSS and IAHSS by analysis of variance (one-way ANOVA) (P>0.05), and has significant difference at 18 months after treatment (P<0.01). There were significant difference in Harris, PAHSS and IAHSS before and after treatment at 18 months (P<0.01). LSD-t was used to analyzed the scoring of Harris, PAHSS and IAHSS, there was significant difference among group A and group B and group C (P>0.05), but no difference between group B and C (P<0.01). There were gastrointestinal reaction in 5 of group A, 35 in group B and 4 in group C.</p><p><b>CONCLUSION</b>The effect of Xiaozhong Zhitong mixture on the prevention of heterotopic ossification after total hip arthroplasty is similar to indomethacin, but Xiaozhong Zhitong mixture has the advantages of less side effects and easily acceptance by patients.</p>

Research progress of bone marrow mesenchymal stem cells differentiation into nerve-like cells induced by traditional Chinese medicine / 中国骨伤

Bone marrow mesenchymal stem cells (MSCs) have active abilities of self-replication and multidifferentiation. In recent years, a lot of studies have proved that MSCs can be induced and differentiated into nerve-like cells under certain conditions. Because of some advaced characteristics including sampling convenience, no immune rejection, high transfection rate and stable exogenous gene expression, MSCs will provide new way in treating disease of nervous system. In this article, the research progress of bone marrow mesenchymal stem cells differentiation into nerve-like cells induced by Traditional Chinese Medicine shall be discussed, and explore the research thinking guided by basis theory of TCM.