Tissue engineering has always been a hot spot in the life science area over the past few years. However, there are some problems, such as the multiplication of seeding cells, the preparation of tissue engineering scaffolds, and the controlled release of drugs from scaffolds and so on. Recently microspheres have been widely used to solve these problems. For example, microspheres are used as microcarriers to culture seeding cells. In addition, microsphers can be either used to prepare engineering scaffolds or directly used as scaffolds. Microspheres can be used to load drugs and control the drug release as well. In this paper the application of microspheres in tissue engineering is reviewed and the up-to-date methods are introduced, including ways of improving performances of microcarriers, preparing scaffolds with microspheres and adding drug-loaded microspheres into scaffolds.

Different human thyroid carcinoma cell lines were treated with all-trans retinoic acid(RA). RA could inhibit cell growth,improve iodide uptake and increase some thyroid specific genes and retinoid acid receptor(RAR)mRNA expressions in FTC-133 cells.However,RA had no effect in C643,HTH74 and XTC. UC1 cells.These findings indicate that different thyroid carcinoma cells display diverse responses to RA.

Objective To investigate the ultrasonic imaging features of thyroid follicular adenoma for conducting the correct diagnosis and differentiation diagnosis.Methods The clinical and imaging data in 64 cases of pathologically proven thyroid follicular adenoma were analyzed on the maximal diameter of tumor,nodularity number,high and low echogenicity,peripheral halo,echo hom-ogeneity,calcifications,and so on.The misdiagnosis causes were investigated.Results The mass was mainly solid or cystic-solid mixed echo.The ultrasonic imaging features of thyroid follicular adenoma were non-peripheral halo or thin wall halo,hyperecho or isoecho,internal macrocalcifications and peripheral calcifications,homogeneous echo structure.Conclusion The ultrasonographic examination can provide the better diagnosis and differentiation diagnosis on thyroid follicular carcinoma.

Objective To explore the change of monocyte chemotactic factor-1 protein(MCP-1)and matrix metalloproteinase-9( MMP-9)of patients with coronary artery disease( CAD)following percutaneous coronary interventional( PCI). Methods Fifty patients underwent PCI procedures for CAD compromising a single coronary artery were selected as PCI group and 30 healthy individuals with normal findings by coronary angiography were selected as the control group. Plasma MCP-1 and MMP-9 were measured in all the subjects. Results The plasma MCP-1 level of patients with CAD after PCI was(19. 87 ± 5. 31)ng/ L,higher than that before operation((15. 71 ± 5. 23)ng/ L,t = 3. 95,P < 0. 01). Whereas in the control group,the MCP-1 level after coronary angiography was(13. 78 ± 5. 58)ng/ L,which was as same as that before operation (12. 42 ± 5. 39 ng/ L,P = 0. 34). Plasma MMP-9 level in the CAD patients after PCI procedures was(22. 69 ± 5. 97)mg/ L,higher than that before operation((19. 52 ± 5. 72)mg/ L,t = 2. 71,P < 0. 01). There was no significant difference in term of plasma MMP-9 level in control group befor and after operation((17. 53 ± 5. 51) mg/ L vs.(16. 69 ± 5. 42)mg/ L,P = 0. 55). Conclusion Plasma MCP-1 and MMP-9 increase in CAD patients following PCI procedures. But their roles in the vascular restenosis following the procedures need further investigation.

Objective To compare the effects of rat proinsulin gene therapy via intraportal infusion and intramuscular injection blood glucose level in streptozotocin-induced diabetic rots. Methods (1) Recombinant eukaryotic cell expression plasmid of rat proinsulin gene pCMV/proiusulin was transferred into streptozotocin-induced diabetic rats by intraportal infusion and intramuscular injection to observe the effect of rat proiusulin gene therapy in diabetic rats. The treatment group by intraportal infusion (group A) and the group by intramuscular injection (group C) were given pCMV/proinsulin naked plasmid DNA 100 μg, while the control groups by intraportal infusion (group B) or by intramuscular injection (group D) were treated with similar amount of pCMV DNA. Normal group and diabetes mellitus group were also observed at the same time. (2) Blood glucose level was tested and serum insulin was determined by radioimmunoassay. RT-PCR and immunohistochemistry were used to detemine proinsulin mRNA and protein expressions in liver and skeletal muscle and protein. Results (1) The blood glucose levels in two treated groups were both decreased. In group A, levels of blood sugar decreased about 7 mmol/L and glycemie control was maintained for 3-4 weeks. Serum insulin levels step up significantly after pCMV/proinsulin gene therapy. The blood glucose level in group A was significantly lower than those of group B and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). In group C, blood glucose levels decreased about 4 mmol/L and glycemic control was maintained for 1-2 weeks. Meanwhile, the concentrations of insulin increased markedly after gene therapy. The blood glucose in group C was significantly lower than those of group D and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). (2) Proinsulin mRNA and protein expressions could be detected in either hepatic cell of group A or skeletal muscle cell of group C, not in group B and group D. Conclusion Proiusulin genetherapy via intraportal infusion or intramuscular injection lowers significantly blood glucose in diabetic rats, and thus offers a potential approach to treatment of diabetes.

Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.

Objective: To investigate the relationship between high sensitivity C-reactive protein (hs-CRP) level and incidence of left atrial spontaneous echocardiographic contrast (LASEC) in the patients with nonvalvular atrial fibrillation (AF). Methods: Four hundred and ninety consecutive patients with nonvalvular atrial fibrillation who underwent radiofrequency ablation for the first time from January 1, 2018 to June 30, 2018 in the Department of Cardiology, Beijing Anzhen Hospital were enrolled. According to the results of transesophageal echocardiography before radiofrequency ablation, patients were divided into the group without LASEC (n=338) and the group with LASEC (n=152). hs-CRP was determined by latex enhanced immunoturbidimetry. The relationship between hs-CRP and LASEC in patients with nonvalvular atrial fibrillation was investigated by univariate and multivariate logistic analysis. Results: LASEC was detected in 152 (31%) of 490 patients. Significant differences in age, type of atrial fibrillation, previous embolic events, fibrinogen, D-dimer, the left atrial anteroposterior diameter and CHA(2)DS(2)-VASc scores were found between patients with and without LASEC (all P<0.05). Compared with the group without LASEC, the serum hs-CRP level was significantly higher in the group with LASEC (3.16 (1.30, 5.23) mg/L vs. 0.67 (0.37, 1.48) mg/L, P<0.001). Multivariate logistic regression analysis showed that hs-CRP (OR=1.136, 95%CI 1.060 - 1.217, P<0.001) and D-dimer (OR=1.040, 95%CI 1.011 - 1.070, P=0.007) were independent determinants for LASEC in this patient cohort. Conclusions: hs-CRP is an independent determinant for LASEC in patients with nonvalvular atrial fibrillation. Inflammation may thus be involved in the formation of prethrombotic state in patients with nonvalvular atrial fibrillation.
Atrial Appendage ; Atrial Fibrillation/epidemiology* ; C-Reactive Protein ; Echocardiography, Transesophageal ; Electrocardiography ; Heart Atria ; Humans ; Incidence ; Risk Factors

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

OBJECTIVESTo study the biological function and its possible underlying mechanism of peroxiredoxin II (PrxII) in liver cancer cell line Hep3B.

METHODSTwo pairs of double-stranded small interfering RNA (siRNA) targeted on PrxII gene were transfected into Hep3B cells using LipofectamineTM 2000. After confirming the inhibited effects of these siRNAs through Quant SYBR Green polymerase chain reaction and Western blot, the biological characters of Hep3B cell were analyzed by flow cytometry analysis, MTT and colony formation assays. Furthermore, dichlorodihydrofluorescein diacetate (DCFH-DA) and thiobarbituric acid (TBA) assays, for measuring the products of oxidative reaction, such as the reactive oxygen species (ROS) and malondialdehyde (MDA), were applied to explore whether the antioxidant mechanism was involved in the effects of PrxII functioning on Hep3B cell.

RESULTSThe two pairs of siRNA significantly inhibited PrxII mRNA and protein expression. Compared to the mock and blank control groups, the two PrxII-silent groups showed decreased rates of cell growth and clone formation and increased rates of cell apoptosis. The numbers of the formed colonies were 42.0+/-2.8 and 40.5+/-0.7 respectively in the two PrxII-silent groups, while they were 121.5+/-2.1 and 130.0+/-1.4 in the mock and blank control groups (P less than 0.05). The levels of endogenous ROS and MDA were significantly higher in the two PrxII-silent groups than those in the mock and blank control groups (P less than 0.05).

CONCLUSIONPrxII might play an important role in the hepatocarcinogenesis, possibly through an antioxidant function which may provide a favorable microenvironment for cancer cell survival and progression.

Cell Line, Tumor ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Oxidative Stress ; Peroxiredoxins ; genetics ; RNA, Small Interfering ; Reactive Oxygen Species ; Signal Transduction ; Transfection

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.