A series of 4-phenyl-pyrrolo[2,3-d] pyrimidine derivatives were synthesized through modifying the structure of the lead compound ruxolitinib by molecular hybridization strategy.It was synthesized from pyrimidine-4,6-diol by Vilsmeier-Haack reaction,SNAr reaction,cyclized,dehydration,Suzuki coupling and finally acylated to give 12 new compounds(12a-121).All structures of the synthesized compounds were confirmed by 1H NMR,13C NMR,and HRMS analysis.The biological activities were evaluated in vitro.Their JAK2 inhibitory activities were studied using JAK2 enzymatic and TF1-GMCSF cellular assays.The results indicated that compounds 12b,12e and 12h showed moderate activity.The anti-tumor activities were studied against JAK2-independent A549 cell line by the MTT assay.Results showed that the tide compounds exhibited potent antiproliferative effect on A549,especially compound 12c(IC50 =0.12 μmol/L),suggesting that this series compounds might be promising anti-tumor agents for futher investigation.

To study the effects of transforming growth factor-beta1/integrin-linked kinase (TGF-beta1/ILK) signal way in interleukin-1beta (IL-1beta)-induced rat tubular epithelial-myofibroblast transdifferentiation (TEMT), and to investigate whether emodin inhibits IL-1beta-induced TEMT through the TGF-beta1/ILK signal way-dependent mechanism.

Objective To investigate the expression and prognostic value of FOXO1 gene in liver cancer tissues based on TCGA and HPA databases. Methods The RNA-seq data of FOXO1 gene in liver cancer were downloaded from TCGA. The difference of FOXO1 gene expression between tumor and adjacent tissues was obtained via R software. The correlation between FOXO1 and clinicopathological features of liver cancer patients was analyzed. Survival analysis was carried out to evaluate the prognostic significance of FOXO1 gene expression in liver cancer patients. Univariate and multivariate Cox analyses were performed to explore prognostic factors. The correlation between FOXO1 expression and TIICs in tumor microenvironment was performed by CIBERSORT. KEGG pathways enrichment analysis was performed for the potential function of FOXO1 gene in liver cancer. Results FOXO1 was downregulated in liver cancer tissues compared with normal tissues (P=1.321E-15). Survival analysis showed that high expression of FOXO1 was positively associated with favorable OS of liver cancer patients (P < 0.05). Clinical stage, T and M stages could be prognostic indicators while FOXO1 wasn't an independent prognostic factor in patients with liver cancer. In TME of liver cancer, the expression of FOXO1 was positively correlated with resting memory CD4 T cells and naive B cells while negatively related to activated memory CD4 T cells and macrophages M2. GSEA identified that FOXO1 participated in multiple cancer-related pathways. Conclusion FOXO1 is down-regulated in liver cancer tissues, and its expression level is associated with OS of patients. FOXO1 might be a biomarker related to the prognosis of liver cancer patients and is expected to be a target for diagnosis and treatment of liver cancer.

Taking JAK2 inhibitor baricitinib and fedratinib as the lead compounds,to design the novel 4-(3-sulfonylbenzene) amino-6-formylpyrrole[2,3-d] pyrimidine JAK2 inhibitors nucleus using the molecular hybrid drug design principle.17 target compounds were synthesized by derivatization of sulfonyl and formyl groups respectively.We used JAK2 kinase and GM-CSF-induced TF-1 cells to measure the activities of compounds.The results showed that most compounds had JAK2 inhibitory activities.Among them,compound 31 had excellent inhibitory activity on JAK2 kinase (IC50 =0.009 μmol/L) and GM-CSF-induced TF-1 cells (IC50 =0.136 μmol/L),which proved that the compound had potential research and development value.

A set of comprehensive chemical experiments was designed for the second-year undergraduate majoring in pharmacy which contained synthesis,refinement,structural identification and appraisal analysis and assaying in phenobarbital.The purpose of the experiment was to improve the comprehensive strength,the ability of investigation and operation.The paper mainly discusses the design and application of the comprehensive experiment in the phenobarbital for pharmacy and Chinese medicine majors from the following aspects including design idea,teaching plan,effectiveness and popularization.

Objective To explore methods to measure the management level of Chinese hospitals in natural conditions of Chinese hospitals, for improvement of their operation efficiency. Methods The methodology of World Management Survey( WMS) was introduced, and the questionnaire was localized using expert consultation method. Double-blind telephone interviews were conducted to investigate the management level of Chinese hospitals in the four dimensions of standardized operation, performance monitoring, target setting and talent management. Results The management level of hospitals in China varied greatly from places. Among them, the hospital management scoring was found to range from 2. 50 to 2. 75 in most cases, averaging 2. 55. These hospitals scored relatively poor at the four specific management practices of hospital layout(2.48), performance communication(2.27), talents retention, and clarity and comparability of objectives(2. 45). Management level of a hospital was correlated to such factors as its history, ownership form, human capital and hospital size. Conclusions This study uses WMS methodology to quantify Chinese hospital management. The overall management level of Chinese hospitals is expected to improve with much gaps to cover. At this stage, it is imperative to solve the unbalanced and inadequate development of hospital management levels, among regions, hospital grades and forms of ownership.

Objective:To explore the safety and efficacy of the minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire and 3D-printed external template technique.Methods:A retrospective study was conducted of the clinical data of 21 patients with unstable pelvic fracture who had undergone minimally invasive treatment at Department of Orthopaedics, Union Hospital from May 2016 to July 2018 using 3D-printed external templates and the blunt head technique of Kirschner wire. There were 7 males and 14 females with an age of 43.6 years (from 19 to 65 years). According to the Tile classification, there were 3 cases of B1, 7 ones of B2, 6 ones of C1 and 5 ones of C2. The intraoperative fluoroscopy, operation time, postoperative fracture reduction and functional recovery of the pelvis at the last follow-up were recorded.Results:The 21 patients were followed up for an average of 16.3 months (from 12 to 24 months). A total of 33 wires were inserted in the 21 patients, including 15 S 1 ones and 18 S 2 ones. The intraoperative fluoroscopy ranged from 13 to 27 times, averaging 21.8 times. The operation time ranged from 65 to 130 min, averaging 88.6 min. The anterior subcutaneous internal fixation was used to fix the anterior ring in 9 patients. No vascular injury occurred during the operation. By the Matta criteria, the postoperative fracture reduction was assessed as excellent in 14 cases, good in 5, and fair in 2, giving an excellent to good rate of 90.5% (19/21). By the Majeed scoring system, the pelvic function at the last follow-up was assessed as excellent in 10 cases, good in 8, and fair in 3, giving an excellent to good rate of 85.7% (18/21). Lateral femoral cutaneous nerve injury occurred in 2 patients but was recovered by the 3-month follow-up. No other complications were follwed up. Conclusion:The minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire assissted by 3D-printed external templates is safe and effective, showing advatages of reduced fluoroscopic frequency and operation time.