As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.

Objective To establish an inhalation infection pneumonia model of C57BL/6J mice with highly virulent and multi-drug resistant Pseudomonas aeruginosa(PA)strain F291007,and to study the microbiological,pathological and immunological characteristics of this model.Methods The strain F291007 was isolated and identified before the bacterial suspension was administered to the mice via aerosolized intratracheal inoculation to establish the pneumonia infection model.In the course of infection,the conditions and survival of the mice were observed,and the bacterial loads,the histopathological states and the cytokine expression levels in the major organs were detected.Finally,three key cytokines were blocked to observe the survival of mice.Results The strain F291007 was isolated and identified.After lethal dose infection,all the mice died within 24 h.After sub-lethal dose infection,a large number of immune cells in the body were capable of phagocytosis and killing of invading pathogens,which was manifested as rapid clearance of bacteria in lungs and the exponential decrease of bacterial load with the passage of time.The pathological changes in lungs were most severe at 1 to 3 days but gradually recovered.After infection,interleukin-6(IL-6),IL-17A and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid and serum were significantly increased at 1 to 3 days.After blocking of these three cytokines with specific antibodies,the survival rates of infected mice decreased significantly.Conclusion A mouse model of gradually-recovered pneumonia infection caused by PA inhalation has been established,suggesting that the first one to three days are critical to immune response after infection through multiple indicators.This mouse model can be used for research on the pathogenesis,immunoregulation and treatment evaluation of highly virulent and multi-drug resistant PA inhalation pneumonia infection.

Objective The molecular mechanism of Yi Lung Xuan Lung Subduing Turbidity Formula in treating rats with vascular dementia(VaD)model was investigated by network pharmacology and animal experiments.Methods The TCMSP database platform was used to screen the active ingredients and related targets of Yi Lung,Xuan Lung and Turbidity Subduing Formula.Since Maitong could not be found in the TCMSP database,the components of Maitong were retrieved by reviewing the literature and using the BATMAN-TCM Bioinformatics Analysis Tool.The GeneCards database was used to obtain VaD-related targets and predict the potential targets of Yi Lung Xuan Lung Turbidity Reducing Formula for the treatment of VaD.The network structure of"active ingredient-target intersection"of the formula was mapped by STRING and Cytoscape 3.7.2 software,and the PPI network model was established to find the key targets.GO enrichment and KEGG pathway enrichment analyses were performed on the targets of VaD treated with Yi Lung Xuan Lung Turbidity Reducing Formula.29 rats were randomly divided into the sham-operation group,the model group,the traditional Chinese medicine group and the western medicine group.The 2-VO method was used for modelling,and the water maze was used to test the memory behaviours of the rats;HE staining was used to observe the pathological changes in the hippocampal CA1 region of the animals in each group,fluorescence detection of VEGF content in the brain of the rats in each group,and ELISA to detect the content of IL-6 and TNF-α in the brain tissues of the rats in each group;Western blot was used to detect the levels of Nrf2,HO-1,P Nrf2,HO-1,P-Akt/Akt and NF-κB.Results A total of 380 targets were obtained from Yi Lung Xuan Lung Turbidity Reducing Formula,and 183 targets were intersected with VaD;The PPI network of intersected core target genes was constructed with 92 nodes and 2610 edges.The GO results suggested that the biological processes related to VaD treatment included responses to lipopolysaccharide,oxidative stress,cell migration,etc.KEGG enrichment analysis suggested that the key pathways included NF-κB,Akt,VEGF,NOD-like receptor signalling.Compared with the model group,the number of crossing platforms in the traditional Chinese medicine group was significantly increased,the histological structure and cellular morphology of hippocampal CA1 area were intact and there were few cellular degeneration,the expression levels of Nrf2,Akt,and HO-1 were significantly increased,and the expression level of NF-κB was significantly decreased(P<0.05),and inflammatory indexes,IL-6 and TNF-α,were significantly down-regulated(P<0.01),and the immunological monoclonal fluorescence showed that the vascular endothelial cell in the traditional Chinese medicine group was significantly increased,while the activity of antioxidant factor SOD increased and the content of oxidative damage factor MDA decreased(P<0.05).Conclusion The network pharmacological analysis suggested that Yi Lung Xuan Lung and Turbidity Reducing Formula could treat VaD by regulating multiple signalling pathways and biological processes.Yi Lung Xuan Lung and Turbidity Reducing Formula increased the protein expression levels of Nrf2,P-Akt/Akt and HO-1,VEGF,and improved the degeneration of neuronal cells of hippocampal CA1 area of rats with VaD,which may be through the activation of AKT/Nrf2/HO-1,and improved the lesions of hippocampal area of VaD,inhibited oxidative damage,and decreased the content of MDA,a factor that can damage oxidative processes.lesions,inhibiting oxidative damage and down-regulating the NF-κB pathway,reducing neuroinflammation,and thus improving cognitive function in VaD model rats.

AIM:To investigate the mechanism by which wogonin(WOG)induces ferroptosis in collagen-in-duced arthritis rat fibroblast-like synoviocytes(rat CIA-FLS cells)through the nuclear factor E2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.METHODS:Rat CIA-FLS cells were divided into:control group,low,medium,and high dose of(25,50 and 100 μmol/L)WOG group,ferroptosis inhibitor(LIP-1)group,LIP-1+high dose WOG group,HO-1 agonist cobalt protoporphyrin(COPP)group,and COPP+high dose WOG group.CCK-8 assay was used for cell viability.Crystal violet staining was used for for cell morphology.The levels of oxidative stress markers gluta-thione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.DCFH-DA fluorescent probe was used to detect the intracellular reactive oxygen species(ROS)content as well as Western blot to detect the protein ex-pression levels of Kelch-like ECH-associated protein 1(KEAP-1),NRF2 and HO-1.RESULTS:Compared with the nor-mal control group,administration of WOG treatment resulted in a significant decrease in CIA-FLS cell viability(P<0.01),a significant increase in the level of oxidative stress(P<0.01),a significant increase in the content of ROS(P<0.01),a significant decrease in the level of expression of NRF2 and HO-1 proteins(P<0.01),and a significant increase in the level of KEAP-1(P<0.01)in the rat.Compared with the WOG group,the LIP-1-treated group showed a significant increase in cell viability(P<0.01),a significant decrease in the level of oxidative stress(P<0.01),and a significant de-crease in the content of ROS(P<0.01).Compared with the WOG group,the addition of COPP resulted in a significant in-crease in the protein expression levels of NRF2 and HO-1(P<0.01)and a significant decrease in KEAP-1 levels(P<0.01).CONCLUSION:WOG can induce ferroptosis in rat CIA-FLS cells by promoting oxidative stress through the NRF2/HO-1 signaling pathway.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

ABSTRACT OBJECTIVE To investigate the current situation of pediatric pharmacist-managed clinic in China, and to provide reference for pediatric pharmacist-managed clinic construction and improvement. METHODS Domestic Children's hospitals, Women's & Children's Hospital, and general hospitals with pediatric unit were selected as the survey objects, questionnaires were distributed through the Wenjuanxing Application, and SPSS 26.0 was used to describe the data. The development of pediatric pharmacist-managed clinic, the qualification of visiting pharmacists, the situation of post training and training needs were analyzed. RESULTS A total of 101 valid questionnaires were collected. Pediatric pharmacist-managed clinics had been set up in 55(54.5%) hospitals, of which 35 were independent pharmacists' clinics, and most had well medical document and patient management processes. However, about 70% of hospitals did not charge registration fees, and more than half of hospitals had fewer than 5 patient-visits per day. 85.5% of the hospitals were visited by clinical pharmacists, and about half of them were senior clinical pharmacists with more than 10 years of working experience. But only 3.6% of visiting pharmacists had the right of specific prescription. In 101 hospitals relevant post training for pharmacists had been carried out in 36 hospitals, of which 25 hospitals had set up pharmacist-managed clinic. In addition to pharmaceutical expertise, more than 50% of pharmacists had a strong demand for the improvement of physician-patient communication and problem-solving ability, and 30%-40% of the demand was focused on the collection of medication history, psychological counseling ability, and case-based learning in the pharmacist-managed clinic. CONCLUSION At present, the domestic pediatric pharmacist-managed clinic shows a vigorous development trend, however, there are insufficient registration fees, visits, and post training. Appropriate service methods of pediatric pharmacist-managed clinic should be actively explored, and a pediatric specialized training system for should be well constructed to improve the competency.

OBJECTIVE: To provide prenatal diagnosis for a pregnant women carrying a chromosome translocations using single nucleotide polymorphism array (SNP-array). METHODS: The fetus and its parents were subjected to chromosome karyotyping and SNP array analysis. RESULTS: A Xp22.12 microduplication was identified in the fetus with a size of 496.3 kb. Search of literature and database indicated the microduplication to be variant of unclear significance. The phenotypically normal mother has carried a 505.8 kb duplication at the same position. The father was normal for the testing. The couple decided to continue with the pregnancy and gave birth to a healthy girl at full-term. No abnormality was found during the follow-up. CONCLUSION The Xp22.12 microduplication encompassed part of RPS6KA3 gene, which shows various features of Coffin-Lowry syndrome. Female with Xp22.12 microduplications may be asymptomatic carriers due to X chromosome inactivation. Our case may provide data for delineating the phenotype-genotype correlation of Xp22.12 microduplication.

The Internet Public Opinion Monitoring and Early Warning System for medical and health industry was designed and implemented due to the frequent occurrence of Internet public opinion, which has all-directional data collecting and analyzing functions, including big data collection, near duplicate detection, spam filtration, key public opinion early warning, region identification and tendency analysis, and can thus provide evidence for relevant departments to take effective measures for the control of Internet public opinion.

Objective To investigate the value of fractional contrast medium bolus injection in improving the quality of CT portography.MethodsA total of 42 patients were randomly divided into two groups which were all given iohexol (350mgI/mL) as the contrast medium.20 patients in the group A were injected with conventional method (dosage of 100ml, rate of 4mL/s).The group B (22 patients) were treated with fractional contrast medium bolus injection, the first phase with 60mL contrast medium (rate of 4mL/s) and the second phase (10s delayed) with 40mL contrast medium (rate of 4m/s).The tube was washed by 20mL saline with the same rate of injection at both phases.The CT values and the image quality of the branches of the portal vein were evaluated according to the original and postprocessed images.Independent samples test was used to compare the CT values of the portal vein, splenic vein, superior mesenteric vein, hepatic parenchyma and portal vein-liver parenchyma.The subjective evaluation scores of the image quality were compared by wilcoxon.ResultsThe CT values of the portal vein, splenic vein and portal vein-liver parenchyma in the group B were significantly higher than that in the group A (t=3.317,3.523,P<0.01).There was no significant difference in CT values of hepatic parenchyma and superior mesenteric vein between the two groups.Subjective quality score in the group B was superior to that in the group A, and the difference was statistically significant.T The two evaluation physicians agreed well.ConclusionThe technique of fractional contrast medium bolus injection can significantly improve the image quality of CT portograghy.

Objective: To study the pathologic features of fallopian tubal epithelium in patients with pelvic high-grade serous carcinoma (HGSC), to investigate its role in pelvic serous carcinogenesis and to reclassify the primary site of HGSC based on recently proposed criteria. Methods: The fallopian tubes in 58 cases of pelvic HGSC (54 cases of ovarian primary, 3 cases of tubal primary, 1 case of peritoneum) and 25 cases of pelvic non-HGSC (5 cases of ovarian low-grade serous cancer, 9 cases of endometrioid cancer, and 11 cases of clear cell ovary carcinoma) were collected from June 2015 to December 2016, and serially examined under light microscope (SEE-FIM protocol). Immunostaining for p53 and Ki-67 was performed to evaluate the presence of p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC) and invasive carcinoma in these fallopian tubes. Meanwhile, primary site of HGSC based on the recently proposed diagnostic criteria were also reclassified. Results: Among the study group, the frequencies of p53 signature, STIL, STIC and invasive HGSC were 27.6% (16/58), 43.1% (25/58), 36.2% (21/58) and 67.2% (39/58), respectively, while in control group, the proportions were 24.0% (6/25), 0, 0 and 8.0% (2/25), respectively. The continuum of epithelial changes in the process of serous neoplasia including p53 signature, STIL, STIC and invasive carcinoma was identified in 8 cases of pelvic HGSC. The proportions of STIL, STIC and invasive carcinomas in HGSC group were higher than that in non-HGSC group (P<0.01). About 80.0% (20/25) of STIL and 85.7% (18/21) of STIC were present unilaterally. Diagnostically, the study group contained the 17 cases of ovarian HGSC, 40 cases of tubal HGSC, and 1 case of peritoneal HGSC after reclassification of the cancer primary. Conclusions Continuous changes of tubal epithelium including p53 signature, STIL, STIC and invasive carcinomas are identified in patients with HGSC, supporting the current understanding that the fallopian tube is likely the cellular source of the majority HGSC. STIL and STIC may be specific to pelvic HGSC and may act as a target for future research on the early detection and prevention of this disease. The newly proposed diagnostic criteria for pelvic HGSC will lead us to more accurate classification of cancer primary sites. Correct classification of HGSC may have potential impacts for cancer prevention and improve our understanding of ovarian serous carcinogenesis.