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

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

OBJECTIVE To explore the feasibility of microfluidic chip in the rapid detection of pesticide residues in Dendrobium officinale. METHODS The sample was extracted with organic solvent, and purified with QuEChERS dispersive SPE, high throughput screening of enzymes for pesticide residue detection from different manufacturers by centrifugal microfluidic chips. The matrix interference was investigated by negative samples with different horizontal adding methods. The sensitivity, repeatability sand accuracy of the microfluidic chip were investigated, and sample results determined by mass spectrometry were compared with them. RESULTS The results revealed that the significant difference rate of rapid detection method was 0.25; the sensitivity was 99.6%; the specificity was 96.4%; the false negative rate was 0.39%; the false positive rate was 3.57%; the accuracy was 98.81%. Two methods of rapid detection of pesticide residues by microfluidic chip and mass spectrometry were used to detect 40 batches of samples. The results indicated that the two methods had a high consistency, compliance rate of testing results were 100%. CONCLUSION Microfluidic chip rapid detection technology can be used for detecting pesticide residues in Dendrobium officinale, which can meet the screening needs of the basic non-professional person to detect the quality of large quantities of pesticide residues.

OBJECTIVE：To study the improvement effects of Weijing deco ction on AECOPD model rats and its possibile mechanism. METHODS ：Totally 55 male SD rats were randomly divided into normal group ，model group ，Weijing decoction low-dose and high-dose groups （8.37，16.74 g/kg，by crude drug ），dexamethasone group （positive control group ，0.09 mg/kg），with 11 rats in each group. Except for normal group ，AECOPD model was induced by cigarettes combined with lipopolysaccharide in other groups. After modeling ，normal group and model group were given constant volume of water intragastrically ，and other groups were given relevant medicine intragastrocally ，twice a day ，for 14 days. After last intragastric administration ，the serum level of IL- 1 β was determined，and pathological changes of lung tissue and bronchus were observed in each group ；mRNA expression of MMP-9 and TIMP- 1 genes in lung tissue were detected ；protein expression of Ras homologous gene family member （RhoA）， dishevelled associated activator of morphogenesis- 1（DAAM1）and hyperplasic suppress gene （HSG）in lung tissue were also determined. RESULTS ：Compared with normal group ，the levels of IL- 1β in serum，mRNA expression of MMP- 9 and TIMP-1 as well as protein expression of RhoA and DAAM 1 in lung tissue were increased significantly in the model group（P＜0.05），while protein expression of HSG in lung tissue was decreased significantly （P＜0.05）；there were many chronic inflammatory cells infiltrating around the bronchus ，some airway mucosa epithelium exfoliating ，alveolar compensatory dilation，pulmonary septal capillary dilation and hyperemia. Compared with model group ，the levels of IL- 1β in serum，mRNA expression of MMP- 9 and TIMP- 1 in lung tissue were decreased significantly in Weijing decoction high-dose group （P＜0.05）；the protein expression of RhoA and DAAM 1 in lung tissue were decreased significantly in Weijing decoction low-dose and high-dose groups（P＜0.05），while the protein expression of HSG in lung tissue was increased （P＜0.05）；the pathological changes of Weijing decoction high-dose group ，such as inflammatory cells infiltrating around the bronchus and shedding of airway mucosa ， were improved significantly ， and there was complete alveolar epithelium structure but no obvious pulmonary dilation. CONCLUSIONS：Weijing decoction can improve AECOPD model rats to certain extent ；its mechanism may be associated with down-regulating mRNA expression of MMP- 9 and TIMP -1 as well as protein expression of RhoA and DAAM 1 in lung tissue ， up-regulating protein expression of HSG in lung tissue so as to inhibit the airway remodeling.

Objective:To explore the application of linkage teaching model between hospitals and colleges based on integration of theory and practice in the course of pediatric nursing skills.Methods:Two undergraduate classes of pediatric nursing in a college in 2017 were selected as the experimental group and the control group by random sampling. The experimental group adopted the combined teaching method of colleges and hospitals based on the integration of truth and practice, while the control group adopted the traditional teaching method. The results of skill operation assessment were compared between the two groups, and the results were evaluated by the self-designed teaching effect evaluation questionnaire.Results:The results of the combined nursing skills teaching in colleges and universities were higher in the experimental group (91.24±3.01) than that in the control group (87.33±2.96), the difference was statistically significant ( t value was 5.027, P<0.05). The evaluation score of teaching effect of the experimental group was 62.61 ± 2.94, which was significantly higher than that of the control group (49.67 ± 7.79) ( t value was 7.965, P<0.05). Conclusions:The combined teaching mode of colleges and hospitals based on the integration of theory and practice is beneficial to improve students′ comprehensive quality and learning effect, further shorten the gap between college theory and clinical practice, and is an effective form of pediatric nursing education.