Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To analyze the mechanism of Biochanin A in the treatment of Gliomas based on network pharmacology and molecular docking.Methods Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),TargetNet,Swiss Target Prediction were used to search the active components and targets of Biochanin A.DisGeNET,GeneCards databases were used to search the corresponding targets of Gliomas.The intersection of active components of Biochanin A and gliomas target were selected to obtain the potential target of Biochanin A in treating Gliomas.Protein gene interaction data were obtained by STRING database,and protein-protein interaction network was constructed by importing into Cytoscape software.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of the same target proteins of drug and disease were carried out by DAVID database.Molecular docking was performed by using DockThor and Pymol software.Results A total of 149 targets of Biochanin A,5654 gliomas relate-genes,97 common targets of Biochanin A and gliomas are collected.The key targets were epidermal growth factor receptor(EGFR),estrogen receptor(ESR1),heat shock protein(HSP)90AA1,matrix metalloproteinase(MMP)9,PPARG and PTGS2.The targets were mainly play an essential role in cell proliferation,invasion,cell apoptosis,and other biological pathways.GO enrichment analysis demonstrated that Biochanin A could involve the treatment of Gliomas in biological process,cell composition and molecular function.KEGG 108 signaling pathways mainly related to pathways in cancer,chemical carcinogenesis-receptor activation,Lipid and atherosclerosis,PI3K/Akt pathway.Molecular docking indicated that Biochanin A had a good bonding activity with the key targets.Conclusion Biochanin A may play a role in the treatment of glioma by inhibiting tumor cell proliferation,inducing apoptosis and enhancing chemotherapy sensitivity.The study built a foundation for drug development and innovative research.

Objective:This study aimed to overview the typical practies made by Europe on rare diseases cooperative researches and provide reference for the construction of rare disease research system in China.Methods:Through literature reviews and official website information, this study systematically summarized the contributions and outputs made by the framework of Europe cooperation in rare disease field.Results:Focusing on the needs of patients, the aim of international cooperation was to improve the ability of ″diagnosis, treatment, research and education″. inclnding multi-sourced special funding and project topic screening, expert networks setup and patient impower, research network construction and mutual promotion, information system modernization, etc.Conclusions:The eco-system of rare disease research in China is still under-construction. It is recommended to combine the characteristics of China′s healthcare system, optimize input strategies, empower patients, innovate mechanism, and speed up bioinformation technology.

Objective:To get comprehensive understanding of the registration characteristics of global clinical trials of coronavirus disease 2019(COVID-19) based on the ClinicalTrials. gov and the Chinese Clinical Trial Registry (ChiCTR).Methods:The clinical trials of COVID-19 in the ClinicalTrials.gov and ChiCTR were retrieved. The search start time was unlimited, with deadlines of 14 December, 2020 and 19 March, 2021, respectively. The registration numbers, registration submitted time, country/region distribution, recruitment status, study types, number of recruits, research phases, and other aspects were analyzed by using bibliometric methods.Results:As of March 19, 2021, there were 775 clinical trials in ChiCTR. As of December 14, 2020, there were 4 137 clinical trials in the ClinicalTrials.gov, and 3 157(76.31%) of the clinical trials recruited subjects who were aged≥18 years old. There were 2 347 intervention trials and 1 759 observational trials. The intervention measures mainly included drugs, biologics and medical devices. The numbers of recruits were 110(48, 308) cases for interventional studies, and 300(100, 1 000) cases for observational trials. The interventional research phases were mainly phaseⅡ (570 items) and phase Ⅲ (358 items). Totally, 50.33%(2 082/4 137) of the clinical trials were under recruitment, 13.10%(542/4 137) had been completed. Among the interventional studies, 729(31.06%) were multi-center studies, with the center numbers of 5(2, 15).Conclusions:At present, there are a large number of clinical trials with various intervention measures in the world. However, the number of recruits is unreasonable, and multi-center study with multi-agency cooperation is insufficient.

Atherosclerosis(AS), characterized with the accumulation of lipids on the vessel wall, is an immune-related inflammatory disease which promotes the progression of cardiovascular diseases(CVD). The imbalance of Treg/Th17 accelerates the progression of AS. Yangyin Huoxue Prescription(YHF)is an efficient traditional Chinese medicine used in the treatment of AS, but the effects of YHF on the balance of immunity have still not been clarified. This project was designed to investigate the effects of YHF on the imbalance of Treg/Th17 and AS in ApoE-/- mice induced by high-fat diet(HFD). ApoE-/- mice were given HFD to induce AS and administered low-dose YHF(18 g/kg)or high-dose YHF(36 g/kg)for 20 weeks. Atherosclerotic plaque area was analyzed by oil red O staining. Serum lipids were measured by biochemical kits. Treg or Th17 cells in peripheral blood were detected by flow cytometry. mRNA and protein expression of Foxp3 and RORγt of aortas were determined by qRT-PCR, Western blot and immunohistochemistry. Splenic CD4+T cells of mice were isolated and activated by anti-CD3/CD28, and then treated with lipopolysaccharide(LPS)and YHF. The expression of mRNA and protein of Foxp3 and RORγt were detected by qRT-PCR and immunofluorescence. It was found that YHF reduced the plaque area, decreased lipid level and increased the ratio of Treg cells in peripheral blood. Moreover, YHF increased mRNA or protein expression of Foxp3 in aortas in vivo or CD4+T cells in vitro while decreasing mRNA or protein expression of RORγt. These results suggested that YHF can regulate the imbalance of Treg/Th17 in ApoE-/- mice induced by HFD, and reduce the inflammatory stimulation of LPS on CD4+T cells, thereby improving AS.

Objective To explore the risk factors of hidden blood loss after UKA.Methods A retrospec-tive study was conducted on 273 patients who underwent UKA from January 2015 to December 2016,including 79 males and 194 females,age between 46 to 87 years old,mean age(67.21± 8.23)years old. The clinical data were collected and the blood volume was calculated according to the Nadler formula. The Gross equation was used to calculate the blood loss and the amount of occult blood loss at 3 days after operation. The risk factors were analyzed statistically. Results The volume of hidden blood loss after operation was(75.36 ± 10.21)mL,and the volume of total blood lost after operation was(187.35± 60.31)mL.Sex,BMI and type of prosthesis were risk factors for hidden blood loss after UKA. Conclusions The volume of hidden blood loss after UKA was related to sex, BMI,and type of prosthesis. For the obese and male patients,we should actively take bleeding management and choose the type of prosthesis reasonably.

Objective To investigate the characteristic of movement disorders,so as to improve their diagnosis and treatment. Methods The clini?cal data of patients with movement disorders that admitted in the dystonia and Botox outpatient department were analyzed. Results Cases of involun?tary movement were significantly more than the primary dystonia,and case of primary hemifacial spasm was dominant(163 cases,61.05%). Among the 66 cases of primary dystonia,blepharospasm was ranked the first(19 cases),the second was spasmodic torticollis(18 cases),and the third was Meige syndrome(12 cases).There was no statistical significance in the gender distribution among primary hemifacial spasm,blepharospasm,spas?modic torticollis and Meige syndrome. Instead,there was statistical significance in the treatment methods(P<0.05),and there was statistical signifi?cance in the mean treatment and onset age(P<0.05). Of the 163 cases with primary hemifacial spasm,the mean onset age was 44.22±12.22 years, and the ratio of men to women was 1∶2.4. There were statistical significances in the mean onset age and duration among the patients with different severity degrees(all P<0.05). Conclusion Primary hemifacial spasm,blepharospasm,spasmodic torticollis and Meige syndrome are the com?mon disease in outpatient department. The primary hemifacial spasm is dominant,women are more than men,and the onset age and/or duration are proportional to the severity degree.

To investigate the effects of Mycobacterium tuberculosis heat shock protein 65(HSP65)on Treg/Th17 immune balance in ApoE-knockout(ApoE-/-)mice, ApoE-/- mice with a high-cholesterol diet were immunized with M. tuberculosis HSP65. Sera were obtained for measurement of anti-HSP65 antibodies by ELISA; the effect of administration of different antigens was investigated, respectively, using flow cytometry analysis on the number of CD4+CD25+Foxp3+Tregs and CD4+IL-17+ Th17; the production of cytokines(IL-10, TGF-β1, IL-17 and IL-21)by these cells were determined by ELISA; total plasma cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were detected by biochemical autoanalyzer. Atherosclerotic lesions were measured by lipid deposition stained with oil red O. The results demonstrated that the levels of anti-HSP65 IgG antibodies were increased significantly in Mycobacterium tuberculosis HSP65-treated ApoE-/- mice, revealed obvious decrease in Treg number, Treg related cytokines(IL-10, TGF-β1)levels and significant increase in Th17 number, Th17 related cytokines(IL-17 and IL-21)levels, the levels of TC, TG, HDL-C and LDL-C did not change between groups, while the atherosclerotic lesions significantly increased. Results indicate that M. tuberculosis HSP65 could interrupt the Th17/Treg immune balance in ApoE-/- mice, suggesting a potential role in the formation and progression of atherosclerosis.

Objective To explore the feasibility using aluminum tripolyphosphate as the synthesis of aspirin model instead of sulfuric acid catalyst. Methods The thermodynamic functions of the reaction system of salicylic acid and acetic anhydride were calculated according to the Benson group contribution method and Joback group contribution method.The enthalpy change,entropy and Gibbs free energy along with the change of temperature as well as the influence of the molar rate of reactants on the equilibrium conversation rate were also studied.Results In the temperature range of 298.15 K to 358.15 K,the reaction enthalpy was less than zero,and was exothermic reaction,and increase of temperature was not conducive to the reaction.The improvement of mole ratio of salicylic acid and acetic anhydride was helpful to improve the equilibrium conversation rate.The theoretical conversion rate could reach 99.58% when the mole ratio of salicylic acid and acetic anhydride was 3.Conclusion From the viewpoint of thermodynamics, the reaction is practical and feasible.

Objective Establish an objective and fair evaluation index system for the implementation effectiveness of the National Major New Drug Development Program of China.Methods Based on literature review and Delphi method,the framework of the evaluation index system was built and analytic hierarchy process was applied to determine the priority of each indicator of the system.The objectiveness and validness of the results were assured by determining expert activeness coefficient,authority coefficient,indicator rationality,and by applying consistency check.Results A targeted and systematic evaluation index system was constructed for the National Major New Drug Development Program,and through expert consultation and analytic hierarchy process,the factor of product result was considered of the highest weight of 39.03％,followed by technical result,theoretical result and organization and management result.The evaluation index system suggested that product result and technical result are two relatively more significant factors to be considered during evaluation.Conclu sion After consultation on expert opinions,the evaluation index system for the National Major New Drug Development Program was constructed with each factor been assigned with a scientific and rational weight,and this will provide a guideline for the decision making of program administrators and evaluation practice.