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[This corrects the article DOI: 10.1016/j.apsb.2022.02.031.].
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Objective:To construct an indicator system to comprehensively evaluate the resource allocation level of the health and pension industry in 31 provinces of China from 2016 to 2021,calculate the fairness of resource allocation,clarify the problems in resource allocation of the health and pension industry in China,and promote high-quality development of the health and pension industry.Methods:The entropy method is used to comprehensively evaluate the level of resource allocation in the health care industry,and the Gini coefficient and Theil index are used to analyze the fairness of resource allocation in the health care industry.Results:The level of resource allocation in the health and pension industry is generally not high,with significant inter provincial differences;the unequal allocation of resources in the health industry is on the rise;regional differences are the leading force that causes differences in the fairness of resource allocation in the health and pension industry.Conclusion:It is suggested to improve the infrastructure and stimulate the endogenous impetus of the development of the health and pension industry;deeply cultivate market demand and improve the level of resource allocation in the health and pension industry;optimize financial investment and bridge the gap in regional health resource allocation.
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A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure-activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.
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PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1. Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1, but did not inhibit any other immune checkpoints. Mechanistically, YPD-29B induced human PD-L1 dimerization and internalization, which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro. YDP-29B was modified as the YPD-30 prodrug to improve druggability. Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells, we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo. Taken together, our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.
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Objective:To analyze the grid management strategy of medical alliances in Rizhao city, Shandong province, and to provide references for improvement of this policy.Methods:In August 2020, semi-structured interviews were conducted with 31 managers of three medical alliances in Rizhao city, regarding the objectives, specific measures, problems and influencing factors of the grid layout of the medical alliances. The grounded theory was used to sort out the interview data, along with the Mazmanian-Sabatier model for further analysis.Results:The analysis resulted in 8 main categories and 19 sub-categories, including theoretical and technical support, target group characteristics, policy causality theory, current status of policy directives, inter-agency relations, socioeconomic conditions and technology, public attitudes, and media campaigns. On this basis, a theoretical framework for the implementation of the grid layout of medical alliance was formed based on the Mazmanian-Sabatier model.Conclusions:The socio-economic conditions and technologies for implementing the grid-based management of medical alliances in Rizhao city were relatively mature, enjoying strong public support and good social response. But on the other hand, there were still such problems as unclear policies, imperfect mechanisms for synergy of interests among different subjects, and incomplete supporting policies. In the future, it is expected to form a policy implementation synergy, introduce supporting policies and strengthen primary teams building, in order to ensure the orderly promotion and long-term implementation of the policy.
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Objective:To construct a Nomogram model in predicting recurrence-free survival (RFS) and overall survival (OS) at six months, one year and two years after hepatocellular carcinoma (HCC) resection by using inflammatory markers combined with other routine clinical indicators.Methods:The data of 314 patients with HCC who underwent first time hepatectomy at Beijing Chaoyang Emergency Rescue Center and Air Force Characteristic Medical Center from January 2013 to January 2018 were analyzed. HCC patients who underwent hepatectomy at the First Medical Center of PLA General Hospital from January 2011 to January 2016 ( n=106) were used as the external validation group. Univariate and multivariate Cox proportional risk model was used to analyze independent risk factors of recurrence and death in HCC patients. A Nomogram model was constructed based on independent risk factors. Validation of the efficacy of the Nomogram model was done based on external data. Results:In the experimental group, 174 patients relapsed. The median RFS was 26 months. The 6 months, 1 year and 2 years RFS were 26.8%, 43.9%, and 68.8%, respectively. A total of 142 patients had died. The median survival time was 30 months. The 6 months, 1 year and 2 years OS were 5.9%, 23.6% and 63.1%, respectively. In the external validation group, 63 patients had developed recurrence, with a median RFS time of 28 months. The 6 months, 1 year and 2 years RFS were 26.4%, 45.3%, 54.7%, respectively. The median survival time was 31 months. The 6 months, 1 year and 2 years OS were 7.5%, 25.5%, 46.6%, respectively. Tumor size (>6.0 cm, HR: 1.447), vascular invasion ( HR: 1.408), TBil (>0.94 mg/dl, HR: 1.949), NLR (>2.54, HR: 2.843), AGR (≤0.88, HR: 2.447) were independent risk factors of HCC recurrence ( P<0.05). Tumor size (>6.0 cm, HR: 2.207), vascular invasion ( HR: 1.529), and NLR (>2.54, HR: 2.708) were independent risk factors of death for HCC patients ( P<0.05). The C-indexes of half-year, one-year and two-year RFS were 0.764 (95% CI: 0.677-0.854), 0.710 (95% CI: 0.615-0.824) and 0.673 (95% CI: 0.601-0.786), respectively. The C-indexes of half-year OS, one-year OS and two-year OS were 0.729 (95% CI: 0.648-0.841), 0.708 (95% CI: 0.608-0.813) and 0.664 (95% CI: 0.618-0.771), respectively. Conclusion:In this study, the construction of a Nomogram model in predicting prognosis of HCC patients was helpful to guide clinicians in improving preoperative treatment plans and in providing ideas for individualized treatment of patients.
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Objective To analyze the effect of FAM172A protein on HepG2 cell proliferation and related signaling pathways,and provide a theoretical basis for the new target of liver cancer treatment.Methods The liver tissue was removed from March 2016 to February 2018 in the Air Force Characteristic Medical Center (formerly the People's Liberation Army Air Force General Hospital).The liver tissues were surgically resected,including normal liver tissue and liver infected with hepatitis B virus (HBV) tissue and liver cancer tissue,HepG2 cells were randomly divided into experimental group and control group.The experimental group was co-transfected with FAM172A protein granules and fluorescent protein-labeled plasmids,and the control group was left without any treatment.The position of FAM172A protein in HepG2 cells was observed by laser confocal microscopy.The content of FAM172A in LO2,HepG2 and HerpG2.2.15 cells was determined.Different concentrations of FAM172A recombinant protein solution were co-incubated with HepG2 cells for different time.Cell cycle and cell count were detected by flow cytometry,and Notch signal and cyclin expression were detected by Western blot.Results The FAM172A protein was located in the endoplasmic reticulum of HepG2 cells and was clearly expressed in normal liver tissues,and was decreased in liver tissues of patients with HBV infection.With the increase of the concentration of FAM172A,the inhibitory effect on the proliferation of hepatoma cells was more obvious,and it was concentration-dependent.After HepG2 cells were treated with 100 pg/L FAM172A for 48 hours,the percentage in the S phase decreased to 2.27% and in the G1 phase increased to 77.49%,the cell cycle was completely blocked in the G1/S phase.Electrophoresis results showed that only the relative expression of Notch3 protein and cyclin E increased.Conclusion FAM172A may be a novel tumor suppressor gene that inhibits the proliferation of hepatoma cells by activating Notch3 signaling pathway and up-regulating the expression of cyclin E.
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Objective To analyze the dilemmas of our hierarchical medical system, in order to seek a viable path for effective implementation.Methods Based on the Meter-horn model, six related factors were used, including policy standards and goals, policy resources, implementation methods, characteristics of the actuator, value orientation of the executive and the system environment, to analyze the dilemmas of the implementation of hierarchical medical system.Results This policy had not achieved the expected effect in the implementation process, which deviated from the original intention of policy designers to some extent. There exist the following setbacks for the roadblocks. For example, policy standard was ambiguous, the policy resources were insufficient, the execution method was not proper, the implementation mechanism was"criticized" , the implementation personnel value orientation was biased and the complex system environment.Conclusions All the factors involved in the implementation of the hierarchical medical policy affect each other.In this consideration, medical institutions at all levels and the relevant departments should coordinate and deal with the relationship between these six related factors, and timely take effective measures to amend and improve the policy, so as to ensure the orderly progress and long-term implementation of the hierarchical medical system.
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Liver three-dimensional technology provides decision-making reference for preoperative assessment,intraoperative simulation,and individualized surgical planning.Compared with traditional imaging techniques,the three-dimensional reconstruction technique of the liver performs real-time three-dimensional image analysis of complex liver tissue,and displays the patient's lesions and surrounding organs and blood vessel structures in three dimensions.This technology opened a new page for liver interventional surgery,especially for the successful implementation of trans-jugular intrahepatic portosystemic shunt (TIPS).This article describes the research progress of liver three-dimensional reconstruction technology and its application in TIPS surgery.
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Objective To make a comprehensive analysis of the satisfaction and preferences of rural doctors'incentive measures,and to identify the incentives that need to be optimized.Methods The method of multi-stage stratified random sampling was used to investigate the rural doctors in Shandong province in 2015.This survey called into play the sample mean and standard deviation for descriptive analysis.And according to Maslow's Hierarchy of Needs theory, the scoring and ranking of different levels and specific incentive measures were calculated.The important quadrant model which combined with motivational preference and satisfaction of incentive measures was used to analysis them.Results The top preference for rural doctors was survival demand,scoring 4 284.Among the specific incentives,the top wss lower medical practice risk,scoring 945.75.In combination with satisfaction analysis, 7 incentive measures, including improving welfare and policy assurance, were now in the state of low satisfaction and high preference. Conclusions In terms of demand level,the survival incentive factor tops the needs of rural doctors.In the specific incentive measures, the seven incentives, such as lower practice risk, deserve more attention. Relevant departments should actively improve and implement these seven measures in order to maximize their motivation for rural doctors.
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Objective To analyze the causes, characteristics and solutions of medical complaints against five tertiary general hospitals in Shandong province, and provide references for the hospitals to improve their quality of care and to build a harmonious relationship between doctors and patients. Methods A retrospective analysis method was used to analyze the causes, solutions and subjects of 1 049 medical complaints against five tertiary general hospitals in Shandong province from 2012 to 2015. Results Among the departments complained, orthopedics(165 cases, 15.7% ), and obstetrics and gynecology(136 cases, 13.0% )topped the rest. The causes of complaints mainly focued on the quality and effect of surgery(355 cases, 33.8% ), diagnosis and treatment(269 cases, 25.6% ), and service attitude(204 cases, 19.4% ). For outpatient/emergency departments, the patients mostly complained on " service attitude" (125 cases, 36.1% ), while the causes of complaints by inpatients were mainly " quality of surgery and effects" (332 cases, 44.8% ). In terms of the dispute solution pathways, consultation between doctors and patients became the most useful one(353 cases, 84.5%), and the third-party mediation approach(56 cases, 13.4% )also played an important role. Conclusions The hospitals should comprehensively strengthen their medical quality management, improve the quality of " service contact" and patient satisfaction. They are also recommended to establish a perfect complaint handling mechanism for higher patient satisfaction. The government should set up specialized courts for medical disputes and improve the efficiency of judicial solution of such disputes.
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Objective To analyze the problems existing in the implementation of the hierarchical medical system in China under the new situation .Methods The Smith policy implementation process model was used as an analytic framework.By means of literature analysis ,stakeholder analysis and PEST analysis ,the analysis was conducted in terms of such elements as the Smith policy implementation process model ,namely ,the idealized policy ,the implementing organization ,the target group and the environmental factors ,as well as its mechanism of action .Results The literature review found that the main obstacle that hinders the smooth implementation of the hierarchical medical system was the lagging of relevant supporting measures ,which accounted for 16.6% (161)of the problems.In addition ,defects in policy design(the lack of division and cooperation mechanism etc .)and constraints in existing institutional mechanism (separation of revenue and expenditure ,unclear orientation ,etc .) were suggested to accelerate the introduction of supporting policies ,respectively accounting for 6.0%(58) and 9.3% (90 ) of the results .Conclusions In the process of policy implementation ,the relationship between the four elements of the ideal policy outcomes ,the implementing organization ,the target group and the environmental factors needs to be coordinated to ensure the effective implementation of the hierarchical medical system .
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Objective To investigate the value of renal CT volumetric texture analysis with machine learning radiomics in assessment of pathological grade of clear cell renal cell carcinoma(ccRCC). Methods Thirty-four biopsy-confirmed ccRCC subjects who had four-phase CT scanning (NC:non-contrast, CM: Corticomedullary, N: Nephrographic, E: Excretory) were collected retrospectively from June 2013 to October 2017 for the study.Non-rigid registration was performed on multi-phase CT images in reference to CM-phase.Each lesion was segmented on CM-phase CT images using our in-house volumetric image analysis platform,"3DQI".A set of fifty-nine volumetric textures,including histogram,gradient,gray level co-occurrence matrix(GLCM),run-length(RL),moments,and shape,was calculated for each segment lesion in each phase as parameters for the training/testing of Random Forest (RF) classifier. Four groups according to pathological Fuhrman grade on a scaleⅠtoⅣ,these tumors were then divided into low(Ⅰ+Ⅱ) and high grade ( Ⅲ + Ⅳ) groups. Feature selection was performed by Boruta algorithm. A 10-fold cross-validation method was applied to validate the RF performance by receiver operating characteristic (ROC) curves analysis to determine the diagnostic accuracy of the model. Results Subjects were divided into four groups by Fuhrman grade on a scaleⅠtoⅣ:3 cases gradeⅠ,19 cases gradeⅡ,8 cases gradeⅢand 4 cases gradeⅣ.In CM-phase,kurtosis and long-run-emphasis(RLE)were selected the most important textures for ccRCC staging among 59 features. The area under curve (AUC) of ROC was 0.88 (79% sensitivity and 82% specificity)by using kurtosis and RLE textures.The mean values of kurtosis and RLE were(-20.00±22.00)×10-2and(3.00±0.40)×10-2for low group,whereas(31.00±32.00)×10-2and(5.00± 0.02)×10-2for high group.Within the mean±SD range of statistics,radiomics can distinguish between low and high grade tumors.In multi-phase analysis,three most important features were selected among 236(59× 4) textures: kurtosis (CM-phase), GLCM homogeneity I (HOMO 1) (E-phase), and GLCM homogeneity 2 (HOMO2)(E-phase).The mean values of HOMO 1(E-phase)and HOMO 2(E-phase)were(19.00±0.03)× 10-2and(11.00±0.02)×10-2for low group,whereas(22.00±0.03)×10-2and(14.00±0.02)×10-2for high group. The AUC was 0.92(93% sensitivity and 87% specificity)by using these three textures. Conclusion This study has demonstrated that renal CT volumetric texture analysis with machine learning radiomics could preoperative accurately perform cancer staging for ccRCC.
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Objective To identify the influencing factors for rural doctors′ training effect,and suggest on the improvement of such training.Methods On the basis of rural doctors′ survey,the theory of pre-intervention was used to probe into the influencing factors for such training in five dimensions of attention notice,mega-cognitive strategies,advance organizer,goal orientation,and preparatory information.Results 73.2% of the groups were found with satisfying effect.In the single factor analysis,comparison of training effect involving such factors as age,gender,length of work life and pre-intervention revealed statistical significance(P<0.05).As shown in the logistic regression analysis,High motivation in meta-cognitive strategies,Clear goals in goal orientation,Tiered and categorized training in advance organizers,and Practical learning in preparatory information,as well as variants like age would influence rural doctors′ training effect significantly.Conclusions The key to better training effect lies in better motivation of the trainee,setting correct training goals,emphasis on the practicability of training contents and,the pertinence of the training objects.
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Objective To study the rural residents′ satisfaction for services of village clinics in Shandong province, identify the influencing factors and put forward feasible suggestions and countermeasures. Methods The method of multi-stage stratified random sampling was used in 54 villages of 18 counties from six prefectures,with 1 590 rural residents randomly sampled for questionnaire survey and interview. This survey called into play the composition ratio for descriptive analysis,and univariate analysis and multinomial logistic regression for identifying the influencing factors. Results The rural residents′overall satisfaction for services of village clinics was acceptable as 65.6% of them were satisfied,yet still at a low level. Major influencing factors for the satisfaction are service attitude and communication ability of rural doctors, drug availability at village clinics, and conditions of equipments and environment. Conclusions Authors proposed such measures as strengthening training of the service attitude and communication ability of rural doctors, scientifically adjusting and refining the types and quantities of essential drugs and continuing to better the conditions of equipments and environment of village clinics. These measures aim at further improving rural residents′satisfaction for services of village clinics.
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Objective To investigate the effects of trace element strontium on the improvement of rat lipid metabolism disor‐der ,prevention and treatment effects on non‐alcoholic fatty acid liver disease (NAFLD) and its possible mechanism .Methods Fifty SD rats were randomly divided into 5 groups .The control group used the common fodder and the other four groups adopted the high fat fodder for 13‐week feeding .During the final 9 weeks ,the strontium 18 mg/L group and the strontium 36 mg/L group were sepa‐rately fed with 18 mg/L and 36 mg/L of strontium water .During the final 4 weeks ,the simvastatin group was gavaged with simvas‐tatin 10 mg/kg .The rats were killed at the end of 14 weeks and the liver index ,serum ALT ,AST ,TG ,TC ,LDL‐C and HDL‐C ,and liver TG ,TC levels were measured .The liver tissue frozen section was performed .The fatty change and its distribution were ob‐served by oil red O staining .Results Compared with the control group ,the liver indexc ,liver TG and TC levels ,serum TC and LDL‐C in the NAFLD model group were statistically increased (P<0 .05);compared with the NAFLD model group ,the levels of serum TC and LDL‐C in the strontium 18 mg/L group were decreased ,but serum HDL‐C was also decreased(P<0 .05);in liver in‐dex ,liver TC and TG levels ,serum TC and LDL‐C in the strontium 36 mg/L group were decreased(P<0 .05) .The oil red O stai‐ning showed that the liver tissue in the NAFLD model group contained a large amount of red staining fat particles ;but which in the strontium 18 mg/L group ,strontium 36 mg/L group and the simvastatin group were decreased to some extents .Conclusion The long term high concentration trace element strontium intake has the effect for improving the rat lipid metabolic disorder and preven‐ting and treating NAFLD .
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Objective To investigate the efficacy of combining ultrasonic with three-dimensional imaging guided microwave ablation in treating large hepatocellular carcinoma.Method The clinical data of 262 patients with large unresectable liver cancer who were admitted to the Air Force General Hospital from Jan 2011 to Jun 2014 were retrospectively analyzed.Of these patients,136 underwent transcatheter arterial chemoembolization (TACE),and the remaining 126 patients underwent combined ultrasonic with three-dimensional imaging guided microwave ablation (MWA).The AFP levels,tumor ablation rate,postoperative complication rates and survival rates between the two groups were compared.Result There were significant differences in the AFP levels in the two groups before and after surgery (P <0.05),but no significant differences were found between the 2 groups (P > 0.05).A significant difference was also observed on tumor ablation rate.In the MWA group,11 patients (8.73%) developed complications,while 21 patients (15.44%) in the TACE group developed complications,(P < 0.05).The 3-month,9-month,1-year,2-year and 3-year survival rates were 99%,95%,81%,70% and 57% in the MWA group,and 98%,94%,63%,36% and 28% in the TACE group.There were significant differences in the 1-year,2-year and 3-year survival rates,but no significant difference were observed in the 3-month and 9-month survival rates.Conclnsion Combined ultrasonic with three-dimensional imaging guided microwave ablation increased the rate of tumor ablation and prolonged the survival time of patients with large hepatocellular carcinoma.
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The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
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Objective:To investigate the synergistic effect and mechanism of the combined application of recombinant human bone morphogenetic protein-2(rhBMP-2) and basic fibroblast growth factor (bFGF).Methods:24KM male mice were randomly divided into6 groups with4 mice in each group, namely,GroupA(control group),GroupB(only treated with collagen),GroupC(treated with 2 ng bFGF+collagen),GroupD(treated with4 μg rhBMP-2+collagen),GroupE(treated with4 μg rhBMP-2+2 ng bFGF+collagen) andGroupF(treated with4 μg rhBMP-2+4 ng bFGF+collagen). The composites were implanted into the intermuscular septum of hind legs mice; whereas in control group, intermuscular septum of mice was separated and no implantation was performed. General observation, detection of concentration of calcium content, micro computed tomography (Micro-CT), three-dimensional reconstruction scan, measurement of bone mineral density(BMD), bone volume fraction(BVF) and trabecular thickness(Tb.Th), as well as histological observation withHE staining andALP andCD34 immumohistochemical staining were performed.Results:Ectopic osteogenesis was found inGroupsD,E andF mice.The difference in concentration of calcium contentswas statistically significant betweenGroupsD andE(P0.05).Micro-CT and three-dimensional reconstruction revealed continuous newborn bone substance in external surface of ectopic bone formation, and the center of bone formation did not show obvious substantial filling by bone substance.The differences in BMD,BVF andTb.Th were statistically significant betweenGroupsD andE orF(P<0.01 or <0.05). HE staining showed that inGroupsD,E andF, newborn bone substance was mainly located at the edge of ectopic bone formation, and the bone formation inGroupsE andF was better than that in GroupD.ALP andCD34 immumohistochemical staining revealed the positive expression mainly at the edge of ectopic bone formation, and area of positiveexpression inGroupsE andF was larger than that inGroupsD.Conclusions:rhBMP-2 possesses the capacity to induce ectopic osteogenesis independently, but bFGF does not have this ability; the combined application of rhBMP-2 and bFGF can enhance the synergetic effect on inducing ectopic osteogenesis.
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A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.