Objective:A mineralized gelatin methacryloyl/hyaluronic acid methacryloyl (GelMA/HAMA) double network hydrogel was constructed, its performance was characterized, and its cell compatibility was studied.Methods:The hydrogel was constructed by photocrosslinking technology, and the biomimetic mineralized hydrogel was prepared by alternating mineralization with calcium and phosphorus solution. The hydrogel was mineralized for three times, for 24 h each time. The control groups were the non-mineralized groups, named the GelMA-0 group and GelMA/HAMA-0 group, respectively. The experimental groups were the mineralized treatment groups. The GelMA hydrogel and GelMA/HAMA double network hydrogel mineralized for 1, 2 and 3 times were named the GelMA-1, 2 and 3 group and GelMA/HAMA-1, 2 and 3 group, respectively. The microstructure of the mineralized hydrogel was characterized by scanning electron microscope and energy dispersive X-ray spectroscopy. The chemical composition of the mineralized hydrogel was characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The mineralization rate of the mineralized hydrogel was evaluated by the ashing method. The compressive strength of the mineralized hydrogel was evaluated by a compression test. The cell compatibility of bone marrow mesenchymal stem cells (BMSCs) on the mineralized hydrogel surface was evaluated by a cell counting kit-8 assay and living/dead cell staining experiment. The datas were analyzed by one-way analysis of variance and Tukey test.Results:With the increase in the number of mineralization cycles, the mineralized layer gradually thickened, and the mineral layer on the cross section of the hydrogel uniformly penetrated into the interior of the hydrogel, with the amount of internal mineral deposition increased. The microstructure of the hydrogel and the distribution of inorganic particles also changed. The surface of the GelMA-3 group and the GelMA/HAMA-3 group contained Ca and P elements, and the distribution was consistent. The inorganic particles generated by mineralization may be immature hydroxyapatite (HAP) crystal precursors. To further verify the chemical composition of inorganic particles, the GelMA-0 and 3 groups as well as the GelMA/HAMA-0 and 3 groups of hydrogels showed GelMA amide Ⅰ, Ⅱ and Ⅲ bands. The GelMA-3 group and GelMA/HAMA-3 group hydrogels contained phosphate, and the diffraction peaks confirmed that the inorganic particles are mainly HAP crystal precursors with low crystallinity. The mineralization rates of the GelMA-1, 2 and 3 groups were (12.48±1.06)%, (21.12±0.62)% and (27.31±0.45)%, while those of the GelMA/HAMA-1, 2 and 3 groups were (15.54±1.03)%, (23.39±0.25)% and (32.26±0.62)%, and the compressive elastic modulus of the GelMA-0, 1, 2 and 3 groups were (69.01±1.04, 91.76±2.05, 105.16±2.95, 131.65±2.21) kPa, and those of the GelMA/HAMA-0, 1, 2 and 3 groups were (270.76±4.56, 347.47±4.60, 388.98±6.96, 430.6±15.47) kPa. Under the same cyclic mineralization times, the mineralization rates and compressive elastic modulus of the GelMA/HAMA double network hydrogel were significantly higher than those of the GelMA hydrogel (all P<0.01). The cell proliferation rates of BMSCs on the GelMA/HAMA-0, 1, 2 and 3 hydrogel surfaces were (49.80±3.38)%, (52.32±1.28)%, (58.00±4.64)% and (62.46±2.74)% on the first day of culture, (58.86±3.36)%, (58.26±3.45)%, (73.08±2.61)% and (76.40±3.45)% on the third day of culture, and (85.89±4.23)%, (90.75±3.21)%, (103.35±4.11)% and (113.42±3.40)% on the fifth day of culture. The cell proliferation rates of the GelMA/HAMA-3 group were significantly higher than those of GelMA/HAMA-0 and 1 groups (all P<0.01). Living/dead cell staining experiment showed that BMSCs on the surface of the GelMA/HAMA-0, 1, 2 and 3 groups were dominated by living cells on the third and fifth days of culture. Conclusions:The mineralized GelMA/HAMA double network hydrogel was constructed, which significantly improved the mineralization rate, mechanical performance and cell compatibility of the biomimetic mineralized hydrogel.

In vivo, cells exist within the mechanical microenvironment of the extracellular matrix (ECM), and their biological processes are regulated by various mechanical factors. However, existing technology limits the direct study of the interaction between cells and ECM in vivo. Using hydrogel to mimic the natural ECM and to construct a suitable mechanical microenvironment for isolated cells, which indirectly reflects the cell-ECM interactions in real organisms through in vitro studies. Thus, in this review, the effects of mechanical factors in hydrogel on different types of cells were summarized, and the development of cell mechanical detection technology using hydrogel as carriers was introduced. Moreover, the future work of using hydrogel to study cell mechanical behavior and related detection technology, as well as standardized preparation, was discussed.

Dynamic hydrogel is three-dimensional networks of hydrophilic polymer formed by dynamic reversible cross-linked bonds. It is widely used in the field of bone repair therapy. The dynamic reversible cross-linked bonds in the dynamic hydrogel endows it with shear-thinning rheological properties, resulting in excellent self-healing, injectability and tunable mechanical properties. In this review, the formation mechanism of dynamic hydrogel was summarized, including non-covalent interaction and dynamic covalent interaction. The advantages and disadvantages of the various cross-linked methods used to form dynamic hydrogel were discussed. The applications of dynamic hydrogel in bone repair therapy were summarized, including haemostasis for filling bone defects, drug delivery, modulation of stem cell behavior, and biomimetic mineralization, to provide a reference for the future development of dynamic hydrogel for bone repair therapy.

Objective:To investigate the effects of transhepatic arterial chemoembolization(TACE)combined with Endostar on CD4+/CD8+T cells,5-aminoketovalonate synthase 1(ALAS1)and HIPPO-YAP signaling pathway in patients with hepatocellular carcinoma(HCC).Methods:A total of 60 HCC patients admitted to Chengdu Third People's Hospital from January 2018 to December 2021 were enrolled and randomly divided into TACE treatment group(A)and TACE combined with Endostar treatment group(B),with 30 patients in each group.T lymphocyte,ALAS1 and indicators of HIPPO-YAP signaling pathway were observed in the two groups.Results:In group A,1 subject had complete remission,2 subjects had partial remission,2 subjects had stable remission,and 4 subjects had progress;in group B,2 subjects had complete remission,4 subjects had partial remission,4 subjects had stable remis-sion,and 1 subject had progress.The total effective rate in group B(33.33%)was significantly higher than that in group A(10.00%),with significant difference among groups(P=0.028).There were no significant differences in CD4+T cells,CD8+T cells and CD4+/CD8+T cells between the two groups before treatment(P=0.972,0.995,0.917).After treatment,level of CD4+T cells in the two groups was significantly increased(P<0.001),while level of CD8+T cells was significantly decreased(P<0.001).CD4+/CD8+T cells was significantly increased(P<0.001),and the changes in group B were significant compared with group A(P<0.001).There was no significant difference in content of ALAS1 between the two groups before treatment(P=0.975);after treatment,content of ALAS1 in liver cancer tissues of the two groups was significantly increased(P<0.001),which in group B was significantly higher than that in group A(P<0.05).Before treatment,there were no significant differences in mammalian STE20-like protein kinase 2(MST2),large tumor suppressor 1(LATS1)and Yes-associated protein(YAP)between the two groups(P=0.134,0.134,0.134).After treatment,mRNA relative expressions of MST2 and LATS1 were significantly increased(all P<0.001),while mRNA relative expression of YAP were significantly decreased(P<0.001),and changes of group B were significant compared with group A(all P<0.001).After treat-ment,there were 5 more cases of no adverse reactions in group B than in group A,and the total incidence of adverse reactions(16.67%)was significantly lower than that in group A(43.33%),with a significant difference between groups(P=0.024).Conclu-sion:TACE combined with Endostar has significant therapeutic effect on HCC patients,which can effectively regulate CD4+/CD8+T cells,promote ALAS1 secretion,and activate HIPPO-YAP signaling pathway.

Objective:To investigate the effects of transhepatic arterial chemoembolization(TACE)combined with Endostar on CD4+/CD8+T cells,5-aminoketovalonate synthase 1(ALAS1)and HIPPO-YAP signaling pathway in patients with hepatocellular carcinoma(HCC).Methods:A total of 60 HCC patients admitted to Chengdu Third People's Hospital from January 2018 to December 2021 were enrolled and randomly divided into TACE treatment group(A)and TACE combined with Endostar treatment group(B),with 30 patients in each group.T lymphocyte,ALAS1 and indicators of HIPPO-YAP signaling pathway were observed in the two groups.Results:In group A,1 subject had complete remission,2 subjects had partial remission,2 subjects had stable remission,and 4 subjects had progress;in group B,2 subjects had complete remission,4 subjects had partial remission,4 subjects had stable remis-sion,and 1 subject had progress.The total effective rate in group B(33.33%)was significantly higher than that in group A(10.00%),with significant difference among groups(P=0.028).There were no significant differences in CD4+T cells,CD8+T cells and CD4+/CD8+T cells between the two groups before treatment(P=0.972,0.995,0.917).After treatment,level of CD4+T cells in the two groups was significantly increased(P<0.001),while level of CD8+T cells was significantly decreased(P<0.001).CD4+/CD8+T cells was significantly increased(P<0.001),and the changes in group B were significant compared with group A(P<0.001).There was no significant difference in content of ALAS1 between the two groups before treatment(P=0.975);after treatment,content of ALAS1 in liver cancer tissues of the two groups was significantly increased(P<0.001),which in group B was significantly higher than that in group A(P<0.05).Before treatment,there were no significant differences in mammalian STE20-like protein kinase 2(MST2),large tumor suppressor 1(LATS1)and Yes-associated protein(YAP)between the two groups(P=0.134,0.134,0.134).After treatment,mRNA relative expressions of MST2 and LATS1 were significantly increased(all P<0.001),while mRNA relative expression of YAP were significantly decreased(P<0.001),and changes of group B were significant compared with group A(all P<0.001).After treat-ment,there were 5 more cases of no adverse reactions in group B than in group A,and the total incidence of adverse reactions(16.67%)was significantly lower than that in group A(43.33%),with a significant difference between groups(P=0.024).Conclu-sion:TACE combined with Endostar has significant therapeutic effect on HCC patients,which can effectively regulate CD4+/CD8+T cells,promote ALAS1 secretion,and activate HIPPO-YAP signaling pathway.

Objective:To explore the application status, research hotspots and frontiers of blended teaching mode in undergraduate nursing education at home and abroad, so as to provide reference for related research.Methods:In Chinese, CNKI, Wanfang Database and VIP, and in English, Web of Science database were used as search sources. CiteSpace was used to conduct a quantitative analysis of the retrieved literatures published from 2008 to 2022.Results:A total of 43 literatures in Chinese and 83 in English were retrieved, and the number of publications showed an overall increasing trend. The research hotspots in China focused on education reform, online learning and curriculum system evaluation, and the research frontiers were network teaching, moral education and humanistic care. Foreign research focused on the choice of education model and emphasizes interaction, and the research frontier were to carry out innovative blended teaching and pay attention to the learning experience and learning environment construction of nursing students.Conclusions:In the future, blended teaching should pay attention to carrying out innovative research and dynamic evaluation and feedback of students' satisfaction. In particular, it is necessary to strengthen the cultivation of blended learning competence among nursing teachers, aiming to promote the knowledge and skills of nursing students, and continuously optimize and innovate the application of blended learning in the field of undergraduate nursing education.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Objective To compare the diagnostic value of MRE and DWI in staging hepatic fibrosis in pa-tients with CHB. Methods In this retrospective analysis ,we investigated 93 patients with CBH and live fibrosis. Ninety-three patients were grouped according to their pathological grading of fibrosis ,from S0 to S4. Sixteen healthy patients were enrolled as the control group. Spearman correlation analysis was used to analyze the correla-tion between the stiffness and ADC value and their staging fibrosis. ROC analysis was conducted to compare the per-formance of the stiffness and ADC value in staging hepatic fibrosis. Results Both liver stiffness value(r=0.962, P<0.01)and ADC value(r=-0.823,P<0.01)were highly correlated with the stage of liver fibrosis. The area un-der ROC(AUC)for the detection of≥S1≥S2/≥S3/S4 stage fibrosis with the stiffness and ADC value were 0.963/0.868、0.995/0.947、0.998/0.948、0.996/0.889 respectively ,with statistically significant differences (P < 0.05 , resectively). Conclusions MRE and DWI have higher value ,and MRE is more accurate than DWI for staging hepatic fibrosis in patients with CHB.

Objective To construct a extracellular matrix-like collagen mimetic peptide-PEG hybrid hydrogel and to study the usage of this hydrogel in 3D culture of rabbit bone marrow mesenchymal stem cells (rBMSCs).Methods The hybrid hydrogel was synthesised by conjugating the cysteine at the end of the collagen mimetic peptide with the maleimine-modified multi-arm PEG.The circular dichroism spectra were used to characterize the triple helix structure and thermal stability of the collagen mimetic peptides.The rheology test and scanning electron microscopy were used to study the gelation process,mechanical strength and internal structure of the hydrogel.The rBMSCs were embedded in the hybrid hydrogel for 3D culture.The cell compatibility of the hydrogel and its effect on differentiation of the cells was studied.Results Collagen mimetic peptides could promote spontaneous formation of triple helix structure in the natural collagen,and the thermal transition temperature was 49.4 ℃.The formation process of the collagen mimetic peptides-PEG hybrid hydrogel was rapid,in which the porous network-like fibrous structure was formed.After the encapsulation of rBMSCs within the hydrogel for 24 h,most of the cells remained viable.Gene expression analysis showed that the hybrid hydrogel could affect the differentiation of rBMSCs.Conclusions The collagen mimetic peptide-PEG hybrid hydrogel possesses the characteristics of mild preparation condition,good mechanical strength and good cell compatibility,and is favorable to chondrocyte differentiation of rBMSCs.

Objective:To study the relationship between genetic polymorphisms of GSTM1 GSTT1 and the susceptibility of laryngeal and hypopharyngeal carcinomas(LHC).Method:The GSTM1 an GSTT1 genotypes were determined by multiplex PCR analysis in 76 LHC patients and 76 population controls.The association be tween the genotypes and LHC risk was measured by odds ratios(ORs)and 95% confidence intervals(95%Cls).Resuit:The frequency of GSTM1 null genotype was 59.2% in the LHC patients and 42.1% in controls(OR=1.935,95%CI=1.069-3.510),the difference was significant(P＜0.01).The frequency of GSTT1 null genotype was 57.9% in the LHC patients and 51.3% in controls.The difference was not significant(P＞0.05).In smokers,the risk of the LHC increased in subjects of GSTM1 null genotype(OR=5.545,95%CI=2.158-13.528).Conclusion:GSTM1 polymorphisms are associated with susceptibility to the LHC.It has the synergistic effects with smoking in the development of the LHC.GSTT1 genotypes might have no association with risk of the LHC in urban Linyi.