BACKGROUND:According to the thrust of document issued by State Drug Administration, the clinical experiment was carried onfufang duzhongjiangu keli (compound) (Bo Si Zhuang) in treatment of knee joint osteoarthritis.OBJECTIVE: To evaluate the improvement of the compound in treatment of knee joint osteoarthritis and its safety.DESIGN: Zhuanggu guanjie wan (bolus) was taken as controlled drug and double blind, double-simulation randomized method was designed.SETTING: Fujian Institute of Chinese Medicine, Guananmen Hospital of China Academy of Traditional Chinese Medicine, Institute of Orthopedics and Traumatology of China Academy of Traditional Chinese Medicine and Beijing Hospital of Chinese Medicine.PARTICIPANTS: Clinical experiment Ⅱ was performed since December 19, 1999, in which, 200 cases of knee joint osteoarthritis were observed and divided into compound group (100 cases) and bolus group (100 cases).From December 1999 to March 2000, clinical experiment Ⅲ was performed to observe 400 cases of knee joint osteoarthritis, in which, 300cases were divided in compound group and 100 cases in bolus group. All of cases were diagnosed by X-ray test and differentiated in Chinese medicine as insufficiency of liver and kidney and stasis of tendons and vessels. All of patients were in the known of experiment.METHODS: In compound group, fufang duzhong zhuanggu keli (1bag/time, 3 times/day) + simulated dosage of zhuanggu guanjie wan were administrated. In bolus group, fufang duzhong zhuanggu keli simulated dosage + zhuanggu guanjie wan (1bag/time, twice/day) were administrated.Double blind and double-simulation randomized control experiment was given in one-month treatment to observe clinical therapeutic effects.MAIN OUTCOME MEASURES: Evaluation on clinical indexes of joint function ,clinical therapeutic effect, syndrome score in Chinese medicine and adverse reaction.RESULTS: Totally 600 cases employed had all accomplished datum collections, no dropped-off case. ① The total effective rate of compound group was superior remarkably to bolus group (92.%, 82%). ② The result of joint function in compound group was superior remarkably to that of bolus group. ③ Concerning to improvement of syndromes in Chinese medicine, the result in compound group was superior to that of bolus group (the decreased integrals were 7.03±3.38 and 5.43±3.16 respectively). ④No obvious harmful effect presented during experiment.CONCLUSION: Fufang duzhong jiangu keli improves the symptoms of osteoarthritis of knee safely and effectively.

AIM: To investigate the effect of extracellular signal-regulated kinase 1/2 signaling pathway after severe diffuse brain injury (DBI) in rats, and to provide base for treatment. METHODS: Male Sprague-Dawley rats were randomly divided into four groups: control group, traumatic group, low dose of inhibitor U0126 treatment group and high dose of inhibitor U0126 treatment group. DBI rat model was established according to the description of Marmarou's diffused brain injury. At 30 min and 1 h, 6 h, 24 h, 48 h and 72 h after injury, morphological changes were observed under light and electronic microscopes. The ERK1/2 phosphorylation and c-Fos were measured by Western blotting. Apoptosis was measured with TUNEL method. Learning and memory function were performed with Morris water maze from 3 days to 7 days after injury. RESULTS: After trauma, some neurons displayed histopathologic changes of necrosis and apoptosis, axon myelin sheath internalization and disconnection. ERK1/2 phosphorylation protein was apparently increased at 30 min after injury, approached peak at 6 h and continued to 24 h. c-fos protein was markedly increased at 30 min after injury, approached peak at 6 h and returned to bottom at 24 h. The number of apoptotic nerve cells increased at 6 h after and approached peak at 72 h. Latencies of searching safety island prolonged. Rats treated with U0126 had reduction in ERK1/2 activity, c-Fos protein, neuronal apoptosis and searching safety island latencies. CONCLUSION: The activated ERK1/2 signaling pathway plays an important role in processing of nerve cell apoptosis after severe DBI.

Objective To establish a new murine model of experimental autoimmune myositis by immunizing with MYBPC2 protein. Methods The purified Myosin-binding protein C, fast type (MYBPC2) was emulsified with complete Freundˊs adjuvant, then C57BL/6 mice were immunized by multi-point subcutaneous injection (0, 7 days), and intraperitoneal injection of pertussis toxin 2 μg simultaneously. The pathological changes of mice with different immunizing dose at the preconceived time were ex-plored. Mean-while, mice were immunized with 600 μg each time, and the muscle endurance was tested on the 21th day. The expression of major histocompatibility complex (MHC) class-Ⅰ and the surface biomarkers of the inflammatory cells in muscle tissues were observed. Mann-Whitney U test was used for statistical analysis. Results ① With the increase of immunizing dosage, muscle damage and inflammation tended to be more serious. On the 21th and 28th day, muscle lesions were most significant. Muscle fiber degeneration and necrosis and inflammatory cell infiltration could be seen in the experimental group. ② Compared with the control group, muscle endurance of mice in the experimental group decreased significantly [(6.1 ±1.3) min versus (9.2±1.6) min, U=2.00, P=0.017]. The MHC class-Ⅰ on the muscle fiber surface of the experimental group was positive, scattered infiltration of CD4 +, CD8+ T ly-mphocytes and CD68 + macrophages between muscle fibers and around the vascular areas could be observed, and CD20+B lymphocytes mainly distributed in the area around the blood vessels, nevertheless rarely seen between muscle fibers. Conclusion Exper-imental autoimmune myositis models of mice have been successfully induced by immunizing with MYBPC2 in China for the first time, and similar clinical and pathological features of human polymyositis could be observed. This new model can be used for studying the pathogenesis of autoimmune myositis.

A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

Objective:To assess the effectiveness and safety of manipulation intervention for degenerative lumbar spondylolisthesis(DLS).Methods:This is a systematic review and meta-analysis.A full-scale retrieval method was performed until February 1,2021,including nine databases.The homogeneity of different studies was summarized using the Review Manager.The quality of studies was determined with the Cochrane risk-of-bias tool.The evidence quality was graded with the Grading of Recommendations,Assessment,Development,and Evaluations approach.Results:A total of 6 studies involving 524 participants were included.The review demonstrated that manipulation has statistically significant improvements for treating DLS according to Japanese Ortho-pedic Association scores(mean difference,3.76;95％confidence interval,2.63 to 4.90;P＜.001)and visual analog scale scores(mean difference,-1.50;95％confidence interval,-1.66 to-1.33;P＜.001)compared to the control group.One study reported that the difference in the Oswestry Disability Index between the traction group and the combination of manipulation and traction group was statistically significant(P＜.05),while another reported that manipulation treatment can significantly improve the lumbar spine rotation angle on X-ray images compared with the baseline data(P＜.05).Moreover,the manipulation group(experimental group)had fewer adverse events than the lumbar traction group(control group).Conclusion:Manipulation intervention is more effective and safer for DLS.Nevertheless,large-scale randomized controlled trials are required to confirm the current conclusions.

Objective: Analyze the clinical application rule of Chinese patent medicine in cervical radiculopathy (CR) .Method: The clinical real-world data of CR were extracted by using information sharing system of traditional Chinese medicine and clinical research. Six hundred and twenty-eight inpatients and out patients with CR were enrolled from December 2012 to July 2014 in the information system database of Wangjing Hospital. The correlation analyses and mutual information value were recorded for Chinese patent medicine therapy application of all patients by using liquorice software. Complex network diagrams were generated. Result: Yuxuebi capsule and Jingshu granule is the highest frequency in application of Chinese patent medicine. Jingshu granule and Cobamamide for injection were the highest frequency in combined application of Chinese patent medicine and western medicine. Association frequency was 822, mutual information value was 268.07. Biqi capsule and Daiwenjiu cream were the highest frequency in combined application of Chinese patent medicine and topical drugs. Association frequency was 384, mutual information value was1754.76. Conclusion: The basic treating principle for CR was promoting blood circulation and removing blood stasis. The efficacy and safety of combined Chinese patent medicine with other medicine need further research

Objective:To evaluate the detection ability of two kinds of high-throughput method to determine neutralizing antibodies based on a microneutralization test (MNT).Methods:Serum samples were collected from the early phase and follow-up period (117 samples in total) for neutralizing antibody testing. They were tested using MNT, pseudovirus neutralization assay (PBNA), competitive inhibition assay (including enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA)) to evaluate the correlation coefficients and threshold values for the effectiveness of these high-throughput neutralizing antibody assays.Results:The correlation coefficients for PBNA, ELISA, and CLIA relative to MNT were 0.760, 0.778, and 0.725, respectively, for individuals infected with 2019-nCoV. The area under the ROC curve was 0.901 for a cutoff value of 50 for the PBNA assay, 0.934 for a cutoff value of 1∶8 for the ELISA assay and 0.838 for a cutoff value of 1.28AU/ml for the CLIA assay when the threshold value for the microneutralization test was taken as 1: 10 (less than 1: 10 is considered negative).Conclusions:The high-throughput method for the detection of COVID-19 neutralizing antibodies are scientific and feasible, and provide an important technical tool for the regular prevention and control of the epidemic.

Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.
Biomarkers ; metabolism ; CD56 Antigen ; genetics ; immunology ; Cell Lineage ; genetics ; immunology ; Dendritic Cells ; immunology ; metabolism ; pathology ; Gene Expression ; Hematologic Neoplasms ; genetics ; immunology ; pathology ; Humans ; Immunophenotyping ; Interferon Type I ; biosynthesis ; metabolism ; Interleukin-12 ; biosynthesis ; metabolism ; Interleukin-3 Receptor alpha Subunit ; genetics ; immunology ; Lectins, C-Type ; genetics ; immunology ; Membrane Glycoproteins ; genetics ; immunology ; Myeloid Cells ; immunology ; metabolism ; pathology ; Receptors, Immunologic ; genetics ; immunology ; Terminology as Topic ; Toll-Like Receptor 4 ; genetics ; immunology ; Toll-Like Receptor 7 ; genetics ; immunology ; Toll-Like Receptor 9 ; genetics ; immunology

Entero virus 71 (EV71) causes hand, foot, and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death. Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71, that mediates viral attachment, internalization, and uncoating. However, the exact binding site of EV71 on SCARB2 is unknown. In this study, we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2. It is named JL2, and it can effectively inhibit EV71 infection of target cells. Using a set of chimeras of human and mouse SCARB2, we identified that the region containing residues 77-113 of human SCARB2 contributes significantly to JL2 binding. The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving α-helices 2, 5, and 14. Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.
Amino Acid Sequence ; Animals ; Antibodies, Monoclonal ; chemistry ; genetics ; metabolism ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Enterovirus A, Human ; drug effects ; genetics ; growth & development ; immunology ; Fibroblasts ; drug effects ; virology ; Gene Expression ; HEK293 Cells ; Humans ; Immunoglobulin Fab Fragments ; chemistry ; genetics ; metabolism ; Lysosome-Associated Membrane Glycoproteins ; chemistry ; genetics ; immunology ; Mice ; Models, Molecular ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Interaction Domains and Motifs ; Receptors, Scavenger ; chemistry ; genetics ; immunology ; Receptors, Virus ; chemistry ; genetics ; immunology ; Recombinant Fusion Proteins ; chemistry ; genetics ; immunology ; Sequence Alignment ; Sequence Homology, Amino Acid ; Sf9 Cells ; Spodoptera ; Thermodynamics

Dendritic Cells ; cytology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; HEK293 Cells ; Humans ; Interferon Regulatory Factor-7 ; metabolism ; Interferon Type I ; metabolism ; Interferon-gamma ; analysis ; Interleukin-6 ; analysis ; Oligonucleotides ; metabolism ; RNA Interference ; RNA, Small Interfering ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Tumor Necrosis Factor ; antagonists & inhibitors ; genetics ; metabolism