Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Application of three-dimensional printing in urology: A recent progress / 第二军医大学学报

Recently, three-dimensional (3D) printing gains a lot of attention in the medical field for its potential benefits in manufacturing low-cost and personalized surgical devices. 3D printing models can be applied in pre-operative planning, surgical training and medical equipment development. Many researches have reported that 3D printing technology and 3D printing materials had been used in the field of urology. 3D printing may be a useful and cost-effective tool in the field of urology in the future. Herein, we reviewed the current applications of 3D printing and outlooked the application prospect of 3D printing technology in the field of urology.

Efficacy of endoscopic papillectomy for tumors of major duodenal papilla and literature review / 中国内镜杂志

Objective To evaluate and analyze the efficacy and safety of endoscopic papillectomy for tumors of major duodenal papilla. Methods The clinical data of three patients with tumors of major duodenal papilla who were treated by endoscopic papillectomy were retrospectively reviewed, and the clinical outcome was summarized. Results The success rate of endoscopic papillectomy was 100.0% (3/3), and the complete resection was 100.0% (3/3). No short-term complication occurred in 3 cases. The recurrence rate was 0.0% (0/3). Conclusion Endoscopic papillectomy is an effective method for treating tumors of major duodenal papilla.

Preparation of curcumin-EC sustained-release composite particles by supercritical CO2 anti-solvent technology / 中国中药杂志

Curcumin-ethyl-cellulose (EC) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading and yield of inclusion complex as evaluation indexes, on the basis of single factor tests, orthogonal experimental design was used to optimize the preparation process of curcumin-EC sustained-release composite particles. The experiments such as drug loading, yield, particle size distribution, electron microscope analysis (SEM) , infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 45 degrees C, crystallization pressure 10 MPa, curcumin concentration 8 g x L(-1), solvent flow rate 0.9 mL x min(-1), and CO2 velocity 4 L x min(-1). Under the optimal conditions, the average drug loading and yield of curcumin-EC sustained-release composite particles were 33.01% and 83.97%, and the average particle size of the particles was 20.632 μm. IR and DSC analysis showed that curcumin might complex with EC. The experiments of in vitro dissolution showed that curcumin-EC composite particles had good sustained-release effect. Curcumin-EC sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Co-immunoprecipitation in screening proteins interacting with CXCR4 during nuclear localization in renal cell carcinoma A498 cells / 第二军医大学学报

Objective To screen for the proteins interacting with CXCR4 during nuclear localization in renal cell carcinoma (RCC) A498 cells. Methods Specific band in co-immunoprecipitation (Co-IP) experiments was sent for mass spectrometry. With the results of Co-IP experiments and mass spectrometry, the proteins interacting with CXCR4 were determined by bioinformatics analyses. Results Three specific bands were found after Co-IP with anti-CXCR4 antibody, and the results of mass spectrometry of the three specific bands showed 36 proteins possibly interacting with CXCR4. Bioinformatics analyses showed that NR1D2, c-src and HSPA8 might interact with CXCR4 and participate in CXCR4 nuclear localization. Conclusion NR1D2, c-src and HSPA8 might have participated in CXCR4 nuclear localization in RCC A498 cells.

Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology / 药学学报

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Reversal effect of LBH589 alone or in combination with bortezomib on drug-resistance in myeloid leukemia and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate reversal effect of histone deacetylase inhibitor LBH589 alone or in combination with proteasome inhibitor bortezomib on drug resistance in acute myeloid leukemia (AML) and its mechanism.</p><p><b>METHODS</b>Ex vivo cultures of HL-60/ADM cells and fresh refractory AML cells were treated with LBH589, bortezomib or their combination at varying concentrations. Proliferation capacity, apoptosis rate and reversal of drug resistance were evaluated by MTT assay, dual staining of Hoechst 33342 and Annexin VFITC/PI by flow cytometry, and adriamycin uptake rate with proliferation inhibition, respectively. The change of signal pathway at protein level was analyzed by Western blot.</p><p><b>RESULTS</b>Synergistic cytotoxicity was observed in the combination treatment with LBH589 and bortezomib against HL-60/ADM cells, as well as the fresh AML cells, the most powerful synergy being observed at 21 nmol/L LBH589 plus 12 nmol/L bortezomib, with CI values of 0.531 and 0.498, respectively by Calcusyn software analysis. Moreover, the accumulation of adriamycin in HL-60/ADM cells was increased more in combination treatment [(64.81 +/- 3.69)%] than in either LBH589 [(28.96 +/- 2.52)%] or bortezomib [(37.29 +/- 3.71)%] alone (P < 0.05), and so did the uptake rate of adriamycin being (64.81 +/- 3.69)%, (28.96 +/- 2.52)% and (37.29 +/- 3.71)% respectively (P < 0.05). The combination treatment induced multiple apoptotic molecules co-action and intracellular drug accumulation contributed to the synergistic cytotoxicity, including caspase activation, PARP cleavage, XIAP downregulation, p53-dependent suppression of Bcl-2 and MRP1 expression via the inhibition of phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor-kappaB (NF-kappaB) signaling pathway.</p><p><b>CONCLUSIONS</b>Combination treatment of drug resistant AML cells with LBH589 and bortezomib produces a synergistic effect of in creating sensitivity to chemotherapy. The mechanism may be mainly resulted from inhibition of PI3K/ Akt/NF-kappaB signaling pathway.</p>

Synthesis and biological evaluation of sorafenib thiourea derivatives / 药学学报

Basing on the market multi-target antitumor agent sorafenib, a series of sixteen 4-[4-(2-methyl-aminoacyl-pyridyl)]oxylphenyl aryl thiourea derivatives were designed and synthesized. Their structures were identified by the spectra of 1H NMR, MS and elemental analysis. The evaluation of antitumor bioactivities in vitro was done by MTT method. It was shown that the synthesized compounds had antitumor activities and compounds 1a, 1d, 1i and 1j showed better or equal antitumor activity on sorafenib.

Synthesis and biological evaluation of 3-aromatic Shiff base-5-fluoroindol-2-one derivatives / 药学学报

Based on the structure of 5-fluoroindol-2-one and fragments from thirteen multi-target tyrosine kinase inhibitors which have been marketed or in the phase of clinical research, eleven 3-aromatic Shiff base-5-fluoroindol-2-one derivatives were designed and synthesized. Their structures were identified by 1H NMR, MS and elemental analysis. In vitro antitumor bioactivities evaluation was done by MTT method. It was shown that most of synthesized compounds had antitumor activities and compounds 1b, 1g, 1i and 1h were better than or equal to the antitumor activity of positive control.

Interaction of Hsc73 with CXCR4 in nuclei of renal cell carcinoma A498 cells / 第二军医大学学报

Objective: To investigate the role of protein Hsc73 (heat shock cognate protein 73 000) in renal cell cancer metastasis promoted by SDF-1/CXCR4 axis, so as to determine whether Hsc73 participates in CXCR4 nuclear localization. Methods: Western blotting analysis was used to observe the expression of Hsc73 in A498 cells over-expressing CXCR4. The location of Hsc73 and the interaction of CXCR4 with Hsc73 were investigated in SDF-1-stimulated A498 cells by immunohistochemical staining, Co-IP (Co-Immunoprecipitation) experiment, etc. Results: Hsc73 was up-regulated in A498 cells over-expressing CXCR4. Hsc73 was mainly found in the cytoplasm of A498 cells; after stimulation with SDF-1, some Hsc73 appeared in the nuclei. Hsc73 protein was found in the nuclei of A498 cells after Co-IP with anti-CXCR4 antibody. Conclusion: Hsc73 as a common molecular chaperone participates in the intra-cellular translocation of CXCR4; Hsc73 also plays a key role in the activation of SDF-1/CXCR4 signal pathway and may be involved in the nuclear translocalization of CXCR4.

A cross-sectional study on knowledge and the ability of hypertension treatment among physicians in district and community hospitals / 中华流行病学杂志

<p><b>OBJECTIVE</b>To estimate the knowledge level and clinical ability of hypertension treatment among physicians in district and community hospitals in big and moderate cities.</p><p><b>METHODS</b>43 district and community hospitals were selected by non-random sampling in Beijing and Baotou inner-Mongolia municipality. A total of 754 physicians in those hospitals were investigated, through an examination.</p><p><b>RESULTS</b>The correct rates on blood pressure stages, risk stratification and treatment strategy were 64%, 28% and 54%, respectively. The knowledge level on non-pharmacologic treatments was insufficient among physicians. The knowledge level of special indications on the common antihypertensive drugs (such as diuretics, beta-blockers, ACE inhibitors) was even worse.</p><p><b>CONCLUSION</b>Physicians in district and community hospitals did not have enough knowledge and ability to fulfill the task of hypertension treatment and management.</p>