ObjectiveTo study the synergistic effect of p38MAPK and ERK1/2 in bone marrow mesenchymal stem cells (BMSCs), and to explore their influence on osteogenic differentiation in BMSCs cultures. MethodsMouse BMSCs were cultured in phenol red-free α-MEM containing osteogenic supplements (OS) for inducing osteogenic differentiation. The temporal sequence of osteogenic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity (ALP) and calcium deposition gene expression. The activation of p38MAPK and ERK1/2 was detected by western blotting using phospho-specific MAP kinase antibody. BMSCs were treated with the inhibitor of p38MAPK pathway(SB203580) or ERK1/2 pathway (PD98059), and osteogenic differentiation was measured. BMSCs were treated with SB203580 or sodium arsenite(ARS), a strong activator of p38MAPK, and the phosphorylation of ERK 1/2 was measured. BMSCs were treated with PP2A inhibitor, Okadaic acid(OA), the phosphorylation of ERK1/2 and osteogenic differentiation were measured. lmmunoprecipitation was used to test the binding interaction between PP2A and ERK1/2, and the effect of SB203580 on the interaction. ResultsTreatment of BMSCs with osteogenic supplements resulted in activation of p38MAPK and ERK1/2 that coincided with osteogenic differentiation. Inhibition of p38MAPK activation by SB203580, blocked the osteogenic differentiation, whereas inhibition of ERK1/2 activation by PD98059, enhanced the osteogenic differentiation in a dose-dependent manner.SB203580 treatment resulted in increased ERK1/2 phosphorylation. By contrast, ARS treatment resulted in decreased ERK1/2 phosphorylation. Inhibition of PP2A by OA resulted in increased ERK1/2 phosphorylation. OS-induced osteogenic differentiation was also attenuated by PP2A inhibition. Immunoprecipitation confirmed the association of PP2A with ERK1/2 in BMSCs cultures, which was decreased by SB203580 treatment. ConclusionThe present study demonstrates a synergistic effect between p38MAPK and ERK1/2 signaling pathways via PP2A in BMSCs cultures, which may regulate the osteogenic differentiation of BMSCs.

Objective To observe the effect of horizontal multi-joint arm continuous passive motion (CPM) training on muscle tension and strength of biceps brachii of patients with stroke. Methods 60 patients with stroke were divided into treatment group (n=30) and control group (n=30). All the patients accepted routine medication and rehabilitation. The treatment group accepted horizontal multi-joint arm CPM training in addition. Their surface electromyography of biceps brachii was analyzed with surface electromyography analysis system: tension and strength before and after treatment. Results The tension and strength of biceps brachii improved in both groups after treatment (P<0.05), and improved more in the treatment group than in the control group (P<0.05). Conclusion The horizontal multi-joint arm CPM training may relieve the muscle tension and enhance the strength of biceps brachii after stroke

Chemical genetics is the science which takes the small molecular compounds as tools to solve the genetics problems or to disturb/adjust normal biological process so as to find out protein functions. Because the small molecules have the diverse chemical characters and the ability to identify the target proteins, they also can be filtrated on the basis of phenotype. So the methods of chemical genetics have been applied in almost all of the researches on biology and medicine. In this paper, the methods to acquire small molecular compounds are introduced. The enormous progress achieved in the field of combinatorial chemistry, which has allowed the rapid production of a large number of chemically diverse molecules, is an important prerequisite to make chemical libraries available to academic researchers. And the applications of the compounds in early embryo development, cell differentiation, on-set and course of disease are discussed, too. The application of small molecules has an enormous impact on our understanding of cell biology. There are many examples where small molecules, in combination with genetic screens, have facilitated the dissection of complex cellular processes.
Combinatorial Chemistry Techniques ; Genetic Techniques ; Genetics ; trends ; Humans ; Molecular Probe Techniques ; Small Molecule Libraries ; chemistry

Objective To evaluate the value of DWI and ADC value in monitoring the chemotherapy response of advanced gastric carcinoma dynamically.Methods 42 advanced gastric carcinoma patients who were confirmed by histopathology underwent T2 WI and DWI examinations at pre-chemotherapy,post-chemotherapy 3 d,7 d,30 d and 60 d respectively.The longest diameters of tumor pre-chemotherapy and post-chemotherapy 60 d were measured on axial T2 WI,meanwhile the ADC values at different time points were calculated.The mean ADC value among pre-and post-chemotherapy of each group (PR and SD)was compared.Results The ADC value of PR group increased gradually.The mean ADC value before therapy was statistically lower than those at differ-ent time points post-chemotherapy (P < 0.05).The ADC value of SD group increased gradually from pre-chemotherapy to post-chemotherapy 30 d,and then the ADC value decreased at post-chemotherapy 60 d.The differences of the mean ADC values in differ-ent time points were statistically significant (P < 0.05).Conclusion DWI and ADC value can dynamically,quantitatively and early detect and monitor the chemotherapy response of advanced gastric carcinoma.

Objective:To produce 161Tb from enriched 160Gd 2O 3 isotope-enriched target material and realize domestic production of the novel medical isotope 161Tb. Methods:The 160Gd 2O 3 isotope-enriched target material was irradiated with neutrons by the China Mianyang Research Reactor (CMRR). The no-carrier-added 161Tb product was obtained after the processes of target broken, sample dissolution, separation and purification with lanthanide (LN) resin and solution replacement with diglycolamide (DGA) column. Various key indicators such as γ spectral purity, metal impurity content, specific activity, radiochemical purity, and radioactive concentration were used to conduct the quality inspection and the control of 161Tb products. Results:161TbCl 3 of 33.4 GBq was obtained in a single time with the radioactive concentration of 16.8 GBq/ml, nuclear purity more than 99.9%, and radiochemical purity of 99.2%. Metal impurity content was met the established standards, with the specific activity of 6.02×10 17 Bq/mol. The radiochemical purities of 161Tb labeling with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) after 0 and 72 h were 100% and 95.8% respectively. Conclusion:The preparation of no-carrier-added 161Tb by using LN resin has the advantages of high separation performance and high sample loading, which has great significance in the field of medical isotope preparation and lays a good nuclide guarantee for the research and development of domestic 161Tb-labeled drugs.

Objective:To investigate the pathogenesis, clinical signs and diagnosing procedures of relapsing polychondritis(RP) in children with airway involvement.Methods:The medical history, clinical symptoms, physical examination, electronic laryngoscopy and imaging findings of six patients were retrospectively analyzed. The patients diagnosed as relapsing polychondritis with involving the airway from January 2018 to December 2021 were in our hospital. The clinical features of the 6 cases were summarized.Results:All 6 patients were male, ranging in age from 8 years 1 month to 14 years 1 month, with a median age of 12.04 years. Stridor and dyspnea were observed in all patients, with hoarseness in 2 patients and frequently nocturnal dyspnea during sleep in 2 patients. Initially, all children were diagnosed as laryngitis or laryngotracheitis, and were treated symptomatically with glucocorticoids and aerosol inhalation. Immunosuppressants and targeted therapy with biologics were given after patients diagnosed as RP. All patients were ultimately required tracheostomy. The time from the onset of airway symptoms to tracheostomy ranged from 1 month to 27 months. Two children had a history of endotracheal intubation prior to tracheostomy. All 6 patients underwent electronic laryngoscopy, revealing involvement of the laryngeal and subglottic mucosa and cartilage structures, which showed gradual improvement with medical therapy. Computed tomography (CT) of the trachea with three-dimensional reconstruction was performed in all patients, demonstrating moderate to severe subglottic stenosis. Two patients exhibited complete airway obstruction at the C4-C6 cervical level. Three children underwent suspension laryngoscopy under general anesthesia and endotracheal mucosal biopsy.Of the 6 children, 3 presented with nasal tip collapse or saddle nose, 2 had auricular cartilage changed, and 1 had scleralinvolvement. One patient underwent PET-CT scanning, which revealed tracheal collapse, diffuse increase in FDG(Flurodeoxyglucose)metabolism with increased FDG uptake in the nasal alar regions. All children were followed up for 2-3 years, 1 child died, while the remaining five continued to receive medical treatment.Conclusions:Relapsing polychondritis with airway involvement has an insidious onset and is difficult to diagnose. The airway stenosisresulting from RP is always severe and necessitating tracheotomy to maintain airway patency in the majority of cases.The treatment coursef or RP is prolonged, requiring long-term tracheostomy tube placement.

OBJECTIVE To investigate the therapeutic effect of autologous costal cartilage transplantation with anterior/posterior split of cricoid cartilage on laryngotracheal stenosis in children.METHODS A retrospective analysis of 12 cases of laryngotracheal stenosis in children treated with anterior/posterior split of cricoid cartilage combined with T-tube implantation in Beijing Children's Hospital Affiliated to Capital Medical University in recent years.There were 5 males and 7 females,aged from 2 years and 6 months to 16 years and 9 months,with an average age of 8 years and 9 months.There were 2 cases of grade Ⅱ stenosis,9 cases of grade Ⅲ stenosis and 1 case of grade Ⅳ stenosis.All cases underwent tracheotomy before operation.The course of disease ranged from 4 months to 6 years,with an average of 3 years.RESULTS Of the 12 patients,10(83.3％)were cured,and the tracheotomy cannula was successfully removed to restore normal breathing and pronunciation function.There were 2 cases of extubation failure,including 1 case of grade Ⅲ stenosis and 1 case of grade Ⅳ stenosis.CONCLUSION The etiology of laryngotracheal stenosis in children is complex and difficult to treat.Anterior/posterior split costal cartilage transplantation combined with T-tube implantation through internal/external cervical approach can achieve good therapeutic effect in the treatment of laryngotracheal stenosis in children.